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Proctitis is an inflammation of the anus & the lining of the

rectum, affecting only the last 6 inches of the rectum. It causes discomfort, bleeding & occasionally a discharge of mucus or pus.

Causes

The cause of proctitis is not known. It is classified as an Inflammatory Bowel Disease (IBD) (such as Crohns disease & ulcerative colitis). It may also occur independently (idiopathic proctitis). Proctitis is also linked to stress & recent studies suggest it can result from intolerance to gluten. Non - sexually transmitted infections causing proctitis are seen less often than STD proctitis. The classical example of non - sexually transmitted infection occurs in children & is caused by the same bacteria that cause strep throat. Autoimmune proctitis is associated with diseases such as ulcerative colitis or Crohns disease. Proctitis may also be caused by certain medications, radiotherapy & inserting harmful substances into the rectum. Risk factors include - Autoimmune disorders
Causes, incidence & risk factors

can also be caused, showing symptoms such as pale skin, irritability, weakness, dizziness, brittle nails & shortness of breath. Bloody stools Constipation Rectal bleeding Rectal discharge, pus Rectal pain or discomfort Tenesmus (pain with bowel movement)
Signs & tests

Examination of stool sample Proctoscopy Rectal culture Sigmoidoscopy

Treatment

There are many causes of proctitis, but they can be grouped in the following categories Autoimmune disease Harmful substances Non - sexually transmitted infection Sexually transmitted disease (STD)
Symptoms

Successful treatment of the underlying cause usually cures the problem. Proctitis caused by infection is treated with antibiotics. Corticosteroids or mesalamine suppositories may relieve symptoms of proctitis in those with Crohns disease or ulcerative colitis. Treatment for proctitis varies depending on severity & the cause. Enema & suppository applications are usually more effective, but some patients may require a combination of oral & rectal applications. Another treatment available is that of fiber supplements such as Metamucil. Taken daily these may restore regularity & reduce pain associated with proctitis.
Prognosis

The probable outcome is good with treatment.

Complications

A common symptom is a continual urge to have a bowel movement - the rectum could feel full or have constipation. Another is tenderness & mild irritation in the rectum & anal region. A serious symptom is pus & blood in the discharge, accompanied by cramps & pain during the bowel movement. If there is severe bleeding, anemia
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Anal fistula Anemia Recto - vaginal fistula (women) Severe bleeding

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Sickle cell disease

Sickle cell disease is an inherited disorder of hemoglobin synthesis. Hemoglobin is a protein inside red blood cells that carries oxygen. Sickle cell anemia is caused by an abnormal type of hemoglobin called hemoglobin S (HbS). Hemoglobin S distorts the shape of red blood cells, especially when exposed to low oxygen levels. The distorted red blood cells are shaped like crescents or sickles. These fragile, sickle - shaped cells deliver less oxygen to the bodys tissues. They can also clog more easily in small blood vessels & break into pieces that disrupt healthy blood flow. Sickle cell anemia is inherited from both parents. It is much more common in people of African & Mediterranean descent. It is also seen in people from South & Central America, the Caribbean & the Middle East. Children who inherit the hemoglobin S gene from one parent & normal hemoglobin (A) from the other parent will have (AS) sickle cell trait. Individuals with sickle cell trait do not have the symptoms of true sickle cell anemia. Sickle cell disease results from a single amino acid substitution (valine for glutamate) in position 6 of the beta - globin chain of hemoglobin. In homozygotes (SS), this genetic alteration yields an unstable RBC with a shortened survival. Hypoxia or hemoconcentration causes the cells to become sickle shaped. The resulting abnormal hemoglobin causes a normocytic, hemolytic anemia with multiple diversely shaped RBCs that are susceptible to morphologically changing into a sickle shape. These sickled cells produce obstruction in small vessels, leading to ischemia & necrosis of distal tissue. Serious complications from visceral ischemia & impaired
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immunity are also common. The abnormal morphology & other cellular characteristics lead to sludging & thrombosis in small vessels with consequent tissue ischemia. Approximately 50% of patients survive beyond the fifth decade. Deaths during an acute crisis may occur in patients who are clinically free of organ failure. Infection is the leading cause of death in children. Strokes & trauma are the leading causes of death in patients aged 10 - 20 years. Children in this age range also die from acute chest syndrome, splenic sequestration crisis & aplastic crisis.

Mortality / Morbidity

History

Patients with sickle cell disease are susceptible to different types of complications at different ages. The history differs according to the nature of the complication.
Acute pain

Pathophysiology

Acute pain due to vaso - occlusive crisis is the most frequent clinical symptom of sickle cell disease in children older than 2 years. The pain may be mild or extremely severe & can affect any area of the body. Severely painful symmetrical swelling of the hands & feet (dactylitis) caused by infarctions of the small bones may be the initial manifestation of sickle cell anemia.
Infection

Patients with SS disease are susceptible to infections because of functional asplenia secondary to auto infarction.
Acute chest crisis

Chest crisis is a common cause of morbidity & mortality in patients with SS disease. Patients present with a new infiltrate on chest radiograph, often with chest pain & fever. Tachycardia, tachypnea & hypoxemia are common.

The pathophysiology is complex, and, in many cases, an inciting factor cannot be identified. Infection (viral or bacterial), pulmonary infarction & fat embolism are the most common. In younger children, infection is the most identified inciting factor.

Abdominal pain

Generalized abdominal pain may occur with diffuse tenderness, distension & muscular rigidity of the abdominal wall.
Splenic sequestration crisis

Vascular occlusion occurs in the splenic sinusoids, resulting in large volumes of blood trapped in the substance of the spleen.
Neurologic disease

Neurologic complications such as cerebral infarction, transient ischemic attack (TIA), intracerebral hemorrhage & spinal cord infarction are common. Presenting complaints depend on the nature of the event & include gait disturbance, hemiparesis, paresthesias, aphasia, altered level of consciousness, or seizures.
Priapism

Heterozygotes (HS) with sickle cell trait typically have erythrocytes that contain only 30 - 40% HbS. Sickling does not occur under physiologic conditions & consequently sickle trait has a generally benign clinical course. In rare cases, hypoxia (such as when flying at high altitudes in an unpressurized aircraft) may cause vaso - occlusive phenomena. Spontaneous hematuria, usually from the left kidney, also occurs in patients with the sickle trait. The bleeding is often mild, but blood transfusion may rarely be needed. Patients with sickle cell disease & trait often have a high incidence of enuresis because their kidneys cannot appropriately concentrate urine.
Physical Symptoms

Priapism may occur at any age but is much more common after puberty. Priapism is defined as a sustained (more than 2 - 4 h) penile erection in the absence of sexual activity or desire. Infants & children are susceptible to aplastic crisis. Aplastic crisis is highly associated with parvovirus B19 infection. Human parvovirus B19 specifically invades proliferating erythroid progenitors. During episodes of crisis, anemia worsens. The patient appears acutely ill, tachycardic & pale.

Symptoms usually dont occur until after age 4 months. Almost all patients with sickle cell anemia have painful episodes (crises), which can last from hours to days. These crises can affect the bones of the back, the long bones & the chest. Some patients have one episode every few years. Others have many episodes per year. The crises can be severe enough to require a hospital stay.
Common symptoms include

Aplastic crisis

Sickle cell trait

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Attacks of abdominal pain Bone pain Breathlessness Delayed growth & puberty Fatigue Fever Paleness Rapid heart rate Ulcers on the lower legs (in adolescents & adults) Yellowing of the eyes & skin (jaundice)

Other symptoms include

Chest pain Excessive thirst Frequent urination Painful & prolonged erection (priapism - occurs in 10 - 40% of men with the disease) Poor eyesight/blindness Strokes Skin ulcers Patients most often present with pain complaints; younger children who cannot communicate well must be observed for irritability, poor feeding, or fussiness. Vital signs should be evaluated for fever, tachycardia & tachypnea. Pulse oximetry should be included when respiratory signs or symptoms are present. Patients usually have icteric sclera & pallor of the conjunctiva & mucous membranes. Cardiac examination often reveals the presence of a murmur due to anemia. Pulmonary auscultation may reveal rales or decreased breath sounds. The presence of active bowel sounds, absence of emesis & patient recognition of pain helps distinguish vaso - occlusive pain from other abdominal etiologies. Inspect the genitalia for priapism if the patient complains of pain.
Causes

More benign factors & environmental changes, such as fatigue, exposure to cold & psychosocial stress, can elicit the sickling process that prompts a crisis. Sepsis Hypovolemic Shock, Shock, Septic Stroke, Ischemic Subarachnoid Hemorrhage Withdrawal Syndromes

Differential diagnosis

Altitude Illness - Pulmonary Syndromes Chronic Anemia, Angioedema Rheumatoid Arthritis, Cholelithiasis Dehydration Pneumonia
Other problems to be considered

Thalassemia
Laboratory Studies

The sickling process that frequently occurs with sickle cell anemia may be precipitated by multiple factors. A crisis may be induced by local tissue hypoxia, dehydration secondary to a viral illness, or nausea & vomiting, all of which lead to hypertonicity of the plasma. Any process that can lead to acidosis, such as infection or extreme dehydration, can cause sickling.
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Baseline abnormalities The patient with homozygous sickle cell disease (SS) typically has a hemoglobin level of 5 - 9 g/dL, with a hematocrit level decreased to 17 - 29%. The total leukocyte count is elevated to 12, 000 - 20, 000 cells/ mm3 (12 - 20 X 109/L), with a predominance of neutrophils. The platelet count is increased & the sedimentation rate is low. The reticulocyte count is usually elevated, but it may vary depending on the extent of baseline hemolysis. Peripheral blood smears demonstrate target cells, elongated cells & characteristic sickle erythrocytes.

Exams & Tests

Tests commonly performed to diagnose & monitor patients with sickle cell anemia include : Complete blood count (CBC) Hemoglobin electrophoresis Sickle cell test
Other tests may include

Bilirubin Blood oxygen CT scan or MRI Peripheral smear Serum creatinine Serum hemoglobin Serum potassium Urinary casts or blood in the urine White blood cell count Pulse oximetry is indicated when pulmonary signs or symptoms are present. In patients with pulmonary symptoms, chest radiography is usually warranted. If an ill - appearing patient presents with pain in the extremities that differs from his or her usual painful episodes, imaging of the affected extremity may be useful. Evaluate any new neurologic changes by performing CNS imaging. CT is usually the preferred initial imaging test.

ibuprofen or acetaminophen. More severe pain can often be controlled at home with oral narcotics. More severe pain usually requires narcotic analgesics.

Acute chest crisis

Imaging Studies

Patients presenting with variable signs of respiratory distress suggestive of acute chest syndrome should be given early & aggressive therapy. Fluids should be given judiciously to avoid pulmonary edema. Pain should be treated. Antibiotic therapy with drugs such as a third - generation cephalosporin & a macrolide. Provide oxygen & respiratory support as needed to relieve hypoxemia. When respiratory distress is moderate to severe, especially with severe anemia, transfusion is appropriate to increase the oxygen - carrying capacity & to decrease the percentage of sickle hemoglobin, thereby diminishing the tendency for intrapulmonary vaso - occlusion.
Acute splenic sequestration

Treatment

Treatment is mainly directed towards prevention of complications & optimization of health.

Emergency Care Painful crisis

For the patient with acute splenic sequestration, therapy is primarily directed at restoring intravascular volume with appropriate isotonic fluids. Severe anemia requires transfusion therapy.

Priapism

In addition to other treatments, treat priapism with analgesia & hydration.

Aplastic crisis

The mainstay of therapy for painful crises is hydration & analgesia. Hydration should be administered to replace ongoing losses & meet maintenance needs, as well as to correct preexisting deficits. Therefore, in most cases, administer intravenous isotonic sodium chloride solution at a rate of 1 - 1.5 times the maintenance rate. Base analgesia on the severity of symptoms, Mild pain can sometimes be controlled at home by giving

Transfusions may be necessary for the patient with aplastic crisis, though the condition often spontaneously resolves within 5 10 days.
Fever

High - risk patients appear toxic, have temperatures > 40 C, or are not receiving prophylactic penicillin. They should receive an intravenous third - generation

cephalosporin & be admitted.

Prevention

Sickle cell anemia can only occur when two people who carry sickle cell trait have a child together. Genetic counseling is recommended for all carriers of sickle cell trait. It is possible to diagnose sickle cell anemia during pregnancy.
Preventing infections

People with sickle cell anemia need to keep their immunizations up to date, including Haemophilus influenza, pneumococcal, meningococcal, hepatitis B & influenza. Some patients may receive antibiotics to prevent infections.

Preventing crises

Parents should encourage children with sickle cell anemia to lead normal lives.
To reduce sickle cell crises, take the following precautions

To prevent oxygen loss, avoid Demanding physical activity (especially if the spleen is enlarged) Emotional stress Environments with low oxygen (high altitudes, non pressurized airplane flights) Smoking Known sources of infection 2) To make sure youre getting enough fluids : Avoid too much exposure to the sun Have fluids on hand, both at home & away 3) To avoid infection Have the child vaccinated as recommended Share the above information with teachers & other caretakers, when necessary Be aware of the effects that chronic, life - threatening illnesses can have on siblings, marriages, parents & the child.
Possible Complications
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1)

Acute chest syndrome Anemia Blindness/vision impairment Brain & nervous system (neurologic) symptoms & stroke Death Disease of many body systems (kidney, liver, lung) Drug (narcotic) abuse Erectile dysfunction (as a result of priapism) Gallstones Hemolytic crisis Infection, including pneumonia, gallbladder inflammation (cholecystitis), bone infection (osteomyelitis) & urinary tract infection Joint destruction Leg sores (ulcers) Loss of function in the spleen Parvovirus B19 infection, leading to low red blood cell production (aplastic crisis) Splenic sequestration syndrome Tissue death in the kidney

Treatments for complications may include

Dialysis or kidney transplant for kidney disease Drug rehabilitation & counseling for psychological complications Gallbladder removal Hip replacement for avascular necrosis of the hip Irrigation or surgery for persistent, painful erections (priapism) Surgery for eye problems Wound care, zinc oxide, or surgery for leg ulcers Bone marrow or stem cell transplants can cure sickle cell anemia. However, transplants have many risks, including infection, rejection & graft - vs - host disease. Therefore, they are currently not an option for most patients. Also, sickle cell anemia patients are often unable to find well - matched donors.

Prognosis

with over folded helix. Child with Down syndrome. Note up - slanting palpebral fissures, bilateral epicanthal folds, a small nose with flat nasal bridge, open mouth with tendency for tongue protrusion & small ears with over folded helix. Pathophysiology

In the past, sickle cell patients often died from organ failure between ages 20 & 40. Due to better understanding & management of the disease, today, patients can live into their 50s or beyond. Causes of death include organ failure & infection. Some people with the disease experience minor, brief, infrequent episodes. Others experience severe, long - term, frequent episodes with many complications.
Hydroxyurea

Chemotherapy agent that allows sickled - shaped blood cells to assume the shape & characteristics of fetal hemoglobin by becoming larger & less adherent, thus allowing travel through the blood vessels to occur easier. 15 - 20 mg/kg/d PO qd initially; may increase by 5 mg/kg/d q12wk until maximum tolerated dose achieved; not to exceed 35 mg/kg/d

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Down syndrome

In 1866, Langdon Down described clinical characteristics of the syndrome that now bears his name. In 1959, Lejeune & Jacobs et al independently determined that trisomy 21 is the cause. Down syndrome is by far the most common & best known chromosomal disorder in humans & the most common cause of intellectual disability. Mental retardation, dysmorphic facial features & other distinctive phenotypic traits characterize the syndrome (see images below for examples).

Infant with Down syndrome. Note up - slanting palpebral fissures, bilateral epicanthal folds, flat nasal bridge, open mouth with tendency of tongue protrusion & small ear
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Down syndrome is the best - known example of a prenatal genetic disorder. In 92 - 95% of cases, Down syndrome is caused by trisomy 21, in which the extra chromosome 21 in the sperm cell results from the nondisjunction in the meiotic stage. When such a gamete becomes fertilized, the fetus will have an extra chromosome 21 in all cells, for a total of 47 chromosomes. 3 5% cases of Down syndrome are caused by translocation, where there are 46 chromosomes, but chromosomal material from 47 chromosomes is present because an extra chromosome 21 is attached (translocated) to another chromosome, usually chromosome 14 (designated as t (14;21)). In another variant, mosaicism, some cells have 47 chromosomes & others have 46 because of an error in one of the first cell divisions of the fertilized egg. Advanced maternal age remains the only well - documented risk factor for maternal meiotic nondisjunction. However, understanding of the basic mechanism behind the maternal age effect is lacking. With a maternal age of 35 years, the risk is 1 in 385. With a maternal age of 40 years, the risk is 1 in 106. With a maternal age of 45 years, the risk is 1 in 30. The characteristic phenotype of Down syndrome is basically the same in trisomy 21 & in translocation. The main features are upward - slanted palpebral fissures (mongoloid slant) a low nasal bridge with epicanthal folds, a small mouth & ears, a single palmar crease (simian crease),


Sex

a flat nasal bridge, short & wide palms, a characteristic dermatoglyphic pattern.

The male - to - female ratio is increased (approximately 1.15 :1) in newborns with Down syndrome. This effect is restricted to free trisomy 21.
Age

2) 3)

Down syndrome can be diagnosed prenatally with amniocentesis, percutaneous umbilical blood sampling (PUBS), chorionic villus sampling (CVS) & extraction of fetal cells from the maternal circulation. Shortly after birth, Down syndrome is diagnosed by recognizing dysmorphic features & the distinctive phenotype.

mobility or head tilt, torticollis, difficulty walking, change in gait pattern, loss of motor skills, incoordination, clumsiness, sensory deficits, spasticity, hyperreflexia, clonus, extensor plantar reflex, loss of upper - body strength, abnormal neurologic reflexes, change in bowel & bladder function, increased muscle tone in the legs & changes in sensation in the hands & feet. These symptoms often remain relatively stable for months or years. In rare cases, the symptoms progress to paraplegia, hemiplegia, quadriplegia, or death.

Physical Growth : Short stature & obesity occurs during adolescence. CNS : Moderate - to - severe mental retardation occurs, with

History

When recording the history from the parents of a child with Down syndrome, the pediatrician should include the following : Parental concern about hearing, vision, developmental delay, respiratory infections & other problems Feeding history to ensure adequate caloric intake Prenatal diagnosis of Down syndrome Vomiting secondary to GI tract blockage by duodenal web or atresia Absence of stools secondary to Hirschsprung disease Delay in cognitive abilities, motor development, language development (specifically expressive skills) & social competence Arrhythmia, fainting episodes, palpitations, or chest pain secondary to heart lesion Symptoms of sleep apnea, including snoring, restlessness during sleep, difficulty awaking, daytime somnolence, behavioral changes & school problems Symptoms of atlanto - axial instability 1) Symptoms include easy fatigability, neck pain, limited neck
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an intelligence quotient (IQ) of 20 - 85 (mean, approximately 50). Hypotonia improves with age. Articulatory problems are present. Sleep apnea occurs when inspiratory airflow from the upper airway to the lungs is impeded for 10 seconds or longer; it often results in hypoxemia or hypercarbia. Behavior : Natural spontaneity, genuine warmth, cheerful, gentleness, patience & tolerance are characteristics. A few patients exhibit anxiety & stubbornness. Seizure disorder (5 - 10 %) : Infantile spasms are the most common seizures observed in infancy, whereas tonic - clonic seizures are most common in older patients. Premature aging : Decreased skin tone, early graying or loss of hair, hypogonadism, cataracts, hearing loss, age - related increase in hypothyroidism, seizures, neoplasms, degenerative vascular disease, loss of adaptive abilities & increased risk of senile dementia of Alzheimer type are observed. Skull : Brachycephaly, microcephaly, a sloping forehead, a flat occiput, large fontanels with late closure, a patent metopic suture, absent frontal & sphenoid sinuses & hypoplasia of the

maxillary sinuses occur.

Eyes : Up - slanting palpebral fissures, bilateral epicanthal folds,

Brushfield spots (speckled iris) Nose : Hypoplastic nasal bone & flat nasal bridge are typical characteristics. Mouth & teeth : An open mouth with a tendency of tongue protrusion, a fissured & furrowed tongue, mouth breathing with drooling, a chapped lower lip, angular cheilitis, partial anodontia (50%), tooth agenesis, malformed teeth, delayed tooth eruption, Ears : The ears are small with an over folded helix Chronic otitis media & hearing loss are common.

2)

Ear of an infant with Down syndrome Note the characteristic small ear with over folded helix Neck - Atlantoaxial instability (14%) can result from laxity of

1)

transverse ligaments that ordinarily hold the odontoid process close to the anterior arch of the atlas. Laxity can cause backward displacement of the odontoid process, leading to spinal cord compression in about 2% of children with Down syndrome. Chest : The inter nipple distance is decreased. Congenital heart defects - Congenital heart defects are common (40 - 50%) Abdomen - Diastasis recti & umbilical hernia occur. GI system (12%) - Duodenal atresia or stenosis, Hirschsprung disease (< 1 %), TE fistula, Meckel diverticulum, imperforate anus & omphalocele are observed. Genitourinary tract : Renal malformations, hypospadias, micropenis & cryptorchidism occur. Skeleton : Short & broad hands, clinodactyly of the fifth fingers with a single flexion crease (20%), hyperextensible finger joints, increased space between the great toe & the second toe & acquired hip dislocation (6%) are typical presentations. Endocrine system Hashimoto thyroiditis that causes hypothyroidism is by far the
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most common acquired thyroid disorder in patients with Down syndrome. The incidence of Graves disease is also increased. Diabetes & decreased fertility can occur. Hematologic system - Children with Down syndrome have an increased risk of developing leukemias, including acute lymphoblastic leukemia & myeloid leukemia; Immunodeficiency - Patients have about a 12 - fold increased risk of infectious diseases, especially pneumonia, because of impaired cellular immunity. Skin - Xerosis, localized hyperkeratotic lesions, elastosis serpiginosa, alopecia areata (< 10%), vitiligo, folliculitis, abscess formation & recurrent skin infections are observed. Dermatoglyphics - Distal axial triradius in the palms, transverse palmar creases, a single flexion crease in the fifth finger, ulnar loops (often 10), a pattern in hypothenar & interdigital III regions are observed. Neurobehavioral disorders - The disorders include attention deficit hyperactivity disorder, oppositional defiant disorder, nonspecific disruptive disorder, autism spectrum disorders & stereotypical movement disorder in prepubertal children with Down syndrome The following studies may be indicated in Down syndrome : Cytogenetic studies : The clinical diagnosis should be confirmed with cytogenetic studies. Karyotyping is essential to determine the risk of recurrence. Interphase fluorescence in situ hybridization (FISH) FISH may be used for rapid diagnosis. It can be successful in both prenatal diagnosis & diagnosis in the neonatal period. Thyroid function tests : Thyroid - stimulating hormone (TSH) & thyroxine (T4) levels should be obtained at birth & annually thereafter. Hematologic tests (i.e. CBC count with differential, bone marrow examination)

Laboratory Studies

Medical Care Genetic counseling

Trisomy 21 : Previous history of trisomy can increase a womans risk for a recurrence. If the couple has a child with trisomy 21, the risk of recurrence is about 1%. The risk does not appear to be increased in siblings of affected individuals.
Vaccination & medication

Usual immunizations & well childcare should be performed Thyroid hormone for hypothyroidism is needed to prevent intellectual deterioration & improve the individuals overall function, academic achievement & vocational abilities. Prompt treatment of respiratory tract infections & otitis media is necessary. Administer anticonvulsants for tonic - clonic seizures or for infantile spasms (treat with steroids). Provide pharmacologic agents, psychotherapy, and/or behavior therapies for psychiatric disorders. Treat skin disorders with weight reduction, proper hygiene, frequent baths, application of antibiotic ointment, or systemic antibiotic therapy. Prevent dental caries & periodontal disease through appropriate dental hygiene, fluoride treatments, good dietary habits & restorative care. Early intervention programs are promising. Programs for infants aged 0 - 3 years are designed to comprehensively monitor & enrich their development by focusing on feeding, as well as gross & fine motor, language, personal & social development. Early intervention techniques may improve the patients social quotient. Overall, positive developmental changes are observed in children with Down syndrome, particularly in terms of their independence, community functioning & quality of life. Perform annual audiologic evaluation.
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Perform annual ophthalmologic evaluations for keratoconus or corneal opacities and/or cataracts. Treat dermatologic issues, such as folliculitis, xerosis, atopic dermatitis, seborrheic dermatitis, fungal infections of skin & nails, vitiligo & alopecia. Prevent obesity by decreasing the patients caloric intake & increasing activity (social & leisure). Screen for celiac disease (symptoms such as constipation, diarrhea, bloating, poor growth, or weight loss) & treat the patient with a gluten - free diet. Swallowing difficulties may persist through the adolescent years & must be addressed. Antibiotic prophylaxis during dental & surgical procedures in the presence of mitral valve prolapse Treatment options should include bone marrow transplantation if leukemia occurs. Treat airway obstruction medically & surgically. Special attention to perioperative modalities because of atlantoaxial instability & problems with the respiratory system. Screen for hypothyroidism & diabetes mellitus. Address concerns regarding menstrual hygiene, sexual abuse, pregnancy & premenstrual syndrome. Manage neurologic problems, including mental retardation, hypotonia, seizures & strokes. Continue speech & language therapy, with a focus on expressive language & intelligibility. Evaluate & treat behavioral problems, such as disruptive behavior disorders, stereotypic behaviors, phobias, elimination difficulties, autism, eating problems, self - injurious behavior & Tourette syndrome. Timely surgery of cardiac anomalies, which are common during the first 6 months of life, may be necessary to prevent serious complications.

Surgical Care

Medical care & monitoring for the adolescent with Down syndrome

Prompt surgical repair is necessary for GI anomalies, such as tracheoesophageal (TE) fistula, pyloric stenosis, duodenal atresia, annular pancreas, aganglionic megacolon & imperforate anus. Adenotonsillectomy may be performed to manage obstructive sleep apnea. Surgical intervention may be necessary to reduce atlantoaxial subluxation & to stabilize the upper segment of the cervical spine if neurologic deficits are clinically significant. In 1942, Klinefelter et al published a report on 9 men who had enlarged breasts, sparse facial & body hair, small testes & an inability to produce sperm. In 1959, these men with Klinefelter syndrome were discovered to have an extra sex chromosome (genotype XXY) instead of the usual male sex complement (genotype XY). Klinefelter syndrome is the most common chromosomal disorder associated with male hypogonadism & infertility. It is defined classically by a 47, XXY karyotype with variants that demonstrate additional X & Y chromosomes. The syndrome is characterized by hypogonadism (small testes, azoospermia, oligospermia), gynecomastia in late puberty, psychosocial problems, hyalinization & fibrosis of the seminiferous tubules & elevated urinary gonadotropin levels.

Adolescent male with Klinefelter syndrome who has female - type distribution of pubic hair & testicular dysgenesis. Pathophysiology

Klinefelter syndrome

Images of physical characteristics seen in Klinefelter syndrome are shown below :

Adolescent male with gynecomastia & Klinefelter syndrome. Child with Klinefelter syndrome. Other than a thin build & disproportionately long arms & legs, the phenotype is normal.

The X chromosome carries genes that play roles in many body systems, including testis function, brain development & growth. The addition of more than one extra X or Y chromosome to a male karyotype results in variable physical & cognitive abnormalities. In general, the extent of phenotypic abnormalities, including mental retardation, is directly related to the number of supernumerary X chromosomes. As the number of X chromosomes increases, somatic & cognitive development are more likely to be affected. Skeletal & cardiovascular abnormalities can become increasingly severe. Gonadal development is particularly susceptible to each additional X chromosome, resulting in seminiferous tubule dysgenesis & infertility, as well as hypoplastic & malformed genitalia in polysomy X males. The major consequences of the extra sex chromosome, usually acquired through an error of nondisjunction during parental gametogenesis, include hypogonadism, gynecomastia & psychosocial problems. Klinefelter syndrome is a form of primary testicular failure, with elevated gonadotropin levels due to lack of feedback inhibition by the pituitary gland. Androgen deficiency causes eunuchoid body proportions; sparse or absent facial, axillary, pubic, or body hair; decreased muscle mass & strength; feminine distribution of adipose tissue; gynecomastia; small testes & penis; diminished libido; decreased physical endurance; & osteoporosis. Men with Klinefelter syndrome are at a higher risk of autoimmune diseases, diabetes mellitus, leg ulcers, osteopenia & osteoporosis, tumors (breast & germ cells), systemic lupus erythematosus, rheumatoid arthritis, and Sjgren syndrome and historically have increased mortality.
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Sex

Because the syndrome is caused by an additional X chromosome on an XY background, this condition affects only males.
Age

Klinefelter syndrome goes undiagnosed in most affected males; among males with known Klinefelter syndrome, many do not receive the diagnosis until they are adults. The most common indications for karyotyping are hypogonadism & infertility.
History

distress. This may be due to poor self - esteem & psychosocial development or a decreased ability to deal with stress. Psychiatric disorders involving anxiety, depression, neurosis & psychosis are more common in this group than in the general population.

Dental

Infertility & gynecomastia are the 2 most common symptoms that lead to diagnosis in patients with Klinefelter syndrome. Other symptoms include fatigue, weakness, erectile dysfunction, osteoporosis, language impairment, academic difficulty, subnormal libido, poor self - esteem & behavioral problems.
Physical Growth

Infants & children achieve normal height, weight & head circumference. About 25% have clinodactyly. Height velocity increases by age 5 years & adults with Klinefelter syndrome are usually taller than adults who do not have the syndrome. Affected individuals also have disproportionately long arms & legs. Most males with the 47, XXY karyotype have normal intelligence. Family background influences intelligence quotient (IQ) score. Subnormal intelligence or mental retardation may be associated with the presence of a higher number of X chromosomes. About 70% of patients have minor developmental & learning disabilities. These may include academic difficulties, delayed speech & language acquisition, diminished short - term memory, decreased data - retrieval skills, reading difficulties, dyslexia & attention deficit disorder. Patients may exhibit behavioral problems & psychological
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About 40% of patients have taurodontism, which is characterized by enlargement of the molar teeth by an extension of the pulp. The incidence rate is about 1% in healthy XY individuals. Although genital abnormalities are not commonly observed in patients with Klinefelter syndrome, the association is important to note because Klinefelter syndrome is one of the causes of genital abnormality or ambiguity. The phenotype include complete sex reversal, true hermaphroditism (e.g. ovotestes), testicular feminization, ambiguous genitalia/under virilization (e.g. hypospadias, micropenis, epispadias, female external genitalia) & mild genital abnormalities.
Cardiac & circulatory problems

CNS

Mitral valve prolapse occurs in 55% of patients. Varicose veins occur in 20 - 40% of patients. The prevalence of venous ulcers is 10 - 20 times higher than in healthy individuals & the risk of deep vein thrombosis & pulmonary embolism is increased.

Causes

In 1959, Klinefelter syndrome was found to be caused by a supernumerary X chromosome in a male. The 47, XXY karyotype of Klinefelter syndrome spontaneously arises when paired X chromosomes fail to separate (nondisjunction in stage I or II of meiosis, during oogenesis or spermatogenesis). Maternal & paternal meiotic nondisjunction each account for approximately 50% of Klinefelter syndrome cases The most common karyotype is 47, XXY, which accounts for 80 - 90% of all cases. Mosaicism (46, XY/47, XXY) is observed in about 10% of cases. Other variant karyotypes, including 48, XXYY;

48, XXXY; 49, XXXYY; & 49, XXXXY, are rare.

Differential diagnosis

Fragile X Syndrome Hypogonadism Marfan Syndrome

Other problems to be considered

recommended in boys with hypotonia or delayed gross motor skills that may affect muscle tone, balance & coordination. Genetic counseling - Physicians should provide parents with information from unbiased follow - up studies of children with Klinefelter syndrome.

Androgen

Kallmann syndrome Infertility

Laboratory studies Cytogenetic studies

Exogenous androgen (testosterone) is the treatment of choice for many aspects of Klinefelter syndrome.
Testosterone enanthate

Klinefelter syndrome may be diagnosed prenatally based on cytogenetic analysis of a fetus. If Klinefelter syndrome is not diagnosed prenatally, the 47, XXY karyotype may manifest as various subtle age - related clinical signs that may prompt chromosomal evaluation. Infants - Hypospadias, small phallus, cryptorchidism, or developmental delay Kindergarten (KG) - aged boys & elementary schoolaged boys - Language delay, learning disabilities, or behavioral problems Older boys & adolescent males - Eunuchoid body habitus, gynecomastia, or small testes The 47, XXY variant is found in 80 - 90% of patients.

Major therapeutic aims are to reduce serum gonadotropin concentrations to the upper limits of normal & to gradually induce virilization.
Pediatric

Beginning at age 11 - 12 years : 50 mg IM qmo; increase dosage annually in accord with the patients state of well - being, degree of virilization, growth & serum gonadotropin levels, eventually reaching adult dose
Edwards syndrome (trisomy 18)

Medical Care

Early identification & anticipatory guidance are extremely helpful, although Klinefelter syndrome is rarely diagnosed in prepubertal males. Treatment should address 3 major facets of the disease : hypogonadism, gynecomastia & psychosocial problems. Androgen therapy - Androgen therapy is the most important aspect of treatment. Speech & behavioral therapy - A multidisciplinary team approach can assist in improving speech impairments, academic difficulties & other psychosocial & behavioral problems. Physical & occupational therapy - Physical therapy should be

Trisomy 18 was independently described by Edwards et al & Smith et al in 1960. Among liveborn children, trisomy 18 is the second most common autosomal trisomy after trisomy 21. The disorder is characterized by severe psychomotor & growth retardation, microcephaly, microphthalmia, malformed ears, micrognathia or retrognathia, microstomia, distinctively clenched fingers & other congenital malformations.

Infant with Edwards syndrome. Note microphthalmia, micrognathia / retrognathia, microstomia, low set/malformed ears, short sternum & abnormal clenched fingers. Note the characteristic clenched hand with the index finger overriding the middle finger & the fifth finger overriding the fourth fingers.
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Note a rocker - bottom foot with prominent calcaneus. Pathophysiology

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Trisomy 18 severely affects all organ systems. In translocations that result in partial trisomy or in cases of mosaic trisomy 18, clinical expression is less severe & survival is usually longer. Approximately 80% of cases occur in females. The preponderance of females with trisomy 18 among liveborn infants (sex ratio, 0.63) compared with fetuses with prenatal diagnoses (sex ratio, 0.90) indicates a prenatal selection against males with trisomy 18 after the time of amniocentesis. Trisomy 18 is detectable during the prenatal & newborn periods.

Sex

Age History

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Prenatal history in trisomy 18 Maternal polyhydramnios possibly related to defective sucking & swallowing reflexes in utero Oligohydramnios secondary to renal defects Disproportionately small placenta Single umbilical artery Intrauterine growth retardation Weak fetal activity Fetal distress Clinical history in trisomy 18 Apneic episodes Poor feeding Marked failure to thrive

Physical Neurological

Delayed psychomotor development & mental retardation (100

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%) Neonatal hypotonia followed by hypertonia, jitteriness, apnea & seizures Malformations (e.g. microcephaly, cerebellar hypoplasia, meningoencephalocele, anencephaly, hydrocephaly, holoprosencephaly, Arnold - Chiari malformation, hypoplasia or aplasia of the corpus callosum, defective falx cerebri, frontal lobe defect, arachnoid cyst, myelomeningocele) Cranial Microcephaly, elongated skull, narrow bifrontal diameter, wide fontanels & prominent occiput Facial Microphthalmia, ocular hypertelorism, epicanthal folds, short palpebral fissures, iris coloboma, cataract, corneal clouding, abnormal retinal pigmentation, short nose with upturned nares, choanal atresia, micrognathia or retrognathia, microstomia, narrow palatal arch, infrequent cleft lip & cleft palate, preauricular tags & low - set & malformed ears (faunlike with flat pinnae & a pointed upper helix) Skeletal Severe growth retardation, characteristic hand posture (i.e. clenched hands with the index finger overriding the middle finger & the fifth finger overriding the fourth finger), camptodactyly, radial hypoplasia or aplasia, thumb aplasia, syndactyly of the second & third digits, arthrogryposis, rocker - bottom feet with prominent calcanei, talipes equinovarus, hypoplastic nails, dorsiflexed great toes, short neck with excessive skin folds, short sternum, narrow pelvis & limited hip abduction Cardiac More than 90% of infants with trisomy 18 have cardiac malformations. Pulmonary Pulmonary hypoplasia & abnormal lobation of the lung GI Omphalocele, malrotation of the intestine, ileal atresia, common mesentery, Meckel diverticulum, esophageal atresia with or without tracheoesophageal fistula, diaphragmatic eventration, prune belly anomaly, diastasis recti, absent

gallbladder, absent appendix, accessory spleens, exstrophy of Cloaca, pyloric stenosis, imperforate or malpositioned anus, pilonidal sinus & hernias (i.e. umbilical, inguinal, diaphragmatic)

Conventional cytogenetic studies

Full trisomy 18 (about 95% of cases) Trisomy 18 mosaicism (about 5% of cases) Translocation type trisomy 18 syndrome (very rare) Medical care in trisomy 18 is supportive. Treat infections as appropriate. These are usually secondary to otitis media, upper respiratory tract infections (e.g. bronchitis, pneumonia) & urinary tract infection. Provide nasogastric & gastrostomy supplementation for feeding problems. Orthopedic management of scoliosis may be needed secondary to hemivertebrae. Cardiac management is primarily medical. Most of these children require a diuretic & digoxin for congestive heart failure. Genetic counseling Recurrence risk is 1% or less for full trisomy 18. If a parent is a balanced carrier of a structural rearrangement, the risk is substantially high. Psychosocial management During the neonatal period, issues of diagnosis & survival are paramount. Parents need information about the syndrome, including its cause, implications & possible outcomes. Support services within the hospital & in the community should be made available to the family. The presence of a disabled child in any family is a source of stress & anxiety. In 1938, Henry Turner first described Turner syndrome, which is one of the most common chromosomal abnormalities. More than 95% of adult women with Turner syndrome exhibit short stature & infertility. Examples of manifestations of

Genitourinary

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Micro multicystic kidneys, double ureters, megalo ureters, hydro ureters, hydronephrosis, horseshoe kidneys & unilateral renal agenesis Cryptorchidism, hypospadias & micropenis in males Hypoplasia of labia & ovaries, bifid uterus, hypoplastic ovaries & clitoral hypertrophy in females Endocrine Thymic hypoplasia, thyroid hypoplasia & adrenal hypoplasia Dermal (i.e. dermatoglyphics) Increased number of simple arches on the fingertips, transverse palmar crease, increased atd angle & clinodactyly of the fifth fingers with a single flexion crease Intellectual capabilities range from profound mental retardation to above - average intelligence. Full trisomy 18 is responsible for 95% of Edwards syndrome cases. Mosaicism & translocations cause few cases. An extra chromosome 18 is responsible for the phenotype. The incidence rate increases with advanced maternal age.

Medical Care

Causes

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Laboratory Studies Hematological studies in patients with trisomy 18 during the first week of life

Thrombocytopenia - This is the most common hematological abnormality detected, occurring in 83% of those with trisomy 18 Neutropenia - This is the second most commonly detected abnormality. Abnormal erythrocyte values - This is the third most common hematological abnormality detected.
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Turner syndrome

Turner syndrome are shown in the images below.

A patient with Turner syndrome. This posterior view shows a low hairline & a shield - shaped chest. Note the narrow hip development. Lymphedema of the feet in an infant. The toes have the characteristic sausagelike appearance. Hyper convex nails in Turner syndrome. Note U - shaped cross section. Pathophysiology

development is absent when ovarian failure occurs before puberty, but pubic hair growth is normal. Diagnosis should be considered in individuals with primary or secondary amenorrhea & in adult women with unexplained infertility, particularly when such individuals also are short in stature.
Physical

Turner syndrome is caused by the absence of one set of genes from the short arm of one X chromosome. In patients with 45, X karyotype, about two thirds are missing the paternal X chromosome.
Sex

Turner syndrome only occurs in females. Noonan syndrome, sometimes inappropriately called male Turner syndrome, can occur in males or females. It is an autosomal dominant genetic disorder & is not a chromosomal disorder. It is unrelated to Turner syndrome.
History

Older individuals may have a history of swollen hands & feet at birth. Children usually present with short stature, but some girls younger than 11 years have heights within the normal range for girls without Turner syndrome. Although the presence of other features may increase the index of suspicion, a karyotype is indicated in any girl with unexplained short stature. In older adolescents & adults, presenting symptoms usually involve issues of puberty & fertility as well as short stature. Adrenarche, the beginning of pubic hair growth, occurs at a normal age & is not an indication that puberty will progress normally. Breast
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Approximately 95% of individuals with Turner syndrome have both short stature & signs of ovarian failure upon physical examination. Short stature - In adults, short stature is due to both a slightly slower growth rate in childhood & to an essentially absent adolescent growth spurt. Before age 11 years, some girls have height & growth rates that are well within the normal range, but heights are below the 50th percentile for girls without Turner syndrome. Dental - A high arched palate suggests the diagnosis. Patients may have dental crowding or malocclusion. Ovarian failure - Suspect ovarian failure in girls who have no breast development by age 12 years or who have not started menses by age 14 years. Elevated levels of luteinizing hormone (LH) & FSH confirm ovarian failure. Pubic hair - Pubic hair development is normal. Nails - Many patients have hypoplastic or hyper convex nails. Although these are not a clinical problem, they are rarely seen in other patients. Nevi - Excessive numbers of nevi, when compared to other family members, are common. These may be removed if rubbed or irritated by clothing, but an increased risk of keloid formation is noted. Webbed neck - Lymphedema in utero can cause a broad neck & a low or indistinct hairline. Cubitus valgus (increased carrying angle) - This is a common skeletal anomaly in girls due to abnormal development of the trochlear head. Other anomalies include short fourth & fifth

metacarpals & metatarsals.

Turner syndrome.
Causes

Short fourth metacarpal or metatarsal - Although this finding is

of minimal clinical significance, it can be a clue to the presence of Turner syndrome. Shield chest - The chest appears to be broad with widely spaced nipples. This may be caused in part by a short sternum. Lymphedema - Lymphedema may be present at any age & is one finding that can suggest Turner syndrome on fetal ultrasonography. Lymphedema is the cause of other anomalies, such as the webbed neck & low posterior hairline. In infants, the combination of dysplastic or hypoplastic nails & lymphedema gives a characteristic sausagelike appearance to the fingers & toes. Eye - Ptosis, strabismus, amblyopia & cataract s are more common in girls with Turner syndrome. Ears - Serous otitis media is more common, probably due to poor anatomic drainage of the middle ear, which may be associated with a high - arched palate. GI bleeding - This is usually due to intestinal vascular malformations, but the incidence of Crohn disease & ulcerative colitis is also increased. Hip dislocation - Infants have a higher incidence of congenital hip dislocation. They should be evaluated clinically & referred for further treatment, if needed. Cutis laxa - Loose folds of skin, particularly in the neck, are signs in newborns. This is a result of resolving lymphedema & occasionally is observed after infancy.
Prenatal signs

The diagnosis of Turner syndrome requires the presence of typical phenotypic features & the complete or partial absence of a second sex chromosome. Advanced maternal age is not associated with an increased incidence. In patients with a single X chromosome, the chromosome is of maternal origin in two thirds of cases. Many of the features of Turner syndrome, including the short stature, are due to the lack of a second SHOX gene, which is on the X chromosome.
Laboratory Studies Diagnosis

Karyotyping is required for diagnosis of Turner syndrome. Diagnosis is confirmed by the presence of a 45, X cell line or a cell line with deletion of the short arm of the X chromosome (Xp deletion). The buccal smear for Barr bodies is obsolete. A male phenotype excludes the diagnosis, regardless of karyotype.

Medical Care

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Most concepti with a 45, X karyotype spontaneously abort. Most, if not all, of those who survive to birth are suspected to have mosaicism for a normal cell line. Turner syndrome may be prenatally diagnosed by amniocentesis or chorionic villous sampling. Neonatal pedal edema suggests a diagnostic evaluation for
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Turner syndrome is a lifelong condition. Most people live long & healthy lives, yet some are susceptible to numerous chronic conditions. In childhood, growth hormone therapy is standard to prevent short stature as an adult. The ideal age for initiating treatment has not been established. Taller adult heights occur with the longest treatment durations before the start of puberty. Estrogen replacement therapy is usually required, but starting too early can compromise adult height. Estrogen is usually started at age 12 - 15 years. Treatment can be started with continuous low dose estrogens at 12 years. These can be cycled in a 3 - week on, 1 - week off regimen after 6 - 18 months; progestin can be added later.

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Thalassemia

A) of

2/ 2.

The thalassemias are inherited disorders of hemoglobin (Hb) synthesis. The word thalassemia is a Greek term derived from thalassa, which means the sea (referring to the Mediterranean) & emia, which means related to blood. Their clinical severity widely varies, ranging from asymptomatic forms to severe or even fatal entities. The name Mediterranean anemia, which Whipple introduced, is misleading because the condition can be found in any part of the world.

A third physiologic Hb, known as Hb A2, is formed by 2/ 2 chains. This Hb appears shortly after birth & remains at a low levels throughout life.
Pathophysiology Globin chain production

Background

In 1925, Thomas Cooley, a Detroit pediatrician, described a severe type of anemia in children of Italian origin. He noted abundant nucleated red blood cells (RBCs) in the peripheral blood, which he initially thought was erythroblastic anemia, an entity that von Jaksh described earlier. Before long, Cooley realized that erythroblastemia is neither specific nor essential in this disorder & that the term erythroblastic anemia was nothing but a diagnostic catchall. Although Cooley was aware of the genetic nature of the disorder, he failed to investigate the apparently healthy parents of the affected children. In recent years, the molecular biology & genetics of the thalassemia syndromes have been described in detail, revealing the wide range of mutations encountered in each type of thalassemia.
Types of haemoglobins 1

To understand the genetic changes that result in thalassemia, one should be familiar with the physiologic process of globin chain production in the healthy individual. The globin chain as a unit is a major building block for Hb : together with heme, it produces the Hb molecule (heme plus globin equals Hb). Two different pairs of globin chains form a tetrameric structure with a heme moiety in the center. All normal Hbs are formed from 2 - like chains & 2 non - chain. Various types of Hb are formed, depending on the types of chains pairing together. Such Hbs exhibit different oxygen - binding characteristics, normally related to the oxygen delivery requirement at different developmental stages in human life.
Sickle cell anemia is a type of qualitative (structural) abnormality of hemoglobin whereas thalassemia is a type of quantitative (haemoglobin production) type of abnormality.

In embryonic life, chains (- like chains) combine with chains to produce Hb Portland ( 2/ 2) & with chains to produce Hb Gower - 1 ( 2/ 2). Subsequently, when chains are produced, they form Hb Gower - 2, pairing with chains ( 2/ 2). Fetal Hb is composed of 2/ 2 & the primary Adult Hb (Hb
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The thalassemias are inherited disorders of Hb synthesis that result from an alteration in the rate of globin chain production. A decrease in the rate of production of a certain globin chain or chains ( , , , ) impedes Hb synthesis & creates an imbalance with the other, normally produced globin chains. Because 2 types of chains (& non - ) pair with each other at a ratio close to 1 :1 to form normal Hbs, an excess of the normally produced type is present & accumulates in the cell as an unstable product, leading to the destruction of the cell. This imbalance is the hallmark of all forms of thalassemia. For this reason, most thalassemias are not considered hemoglobinopathies because the globin chains are normal in structure & because the defect is limited to a decreased rate of production of these normal chains. The type of thalassemia usually carries the name of the under

produced chain or chains. The reduction varies from a slight decrease to a complete absence of production. For example, when chains are produced at a lower rate, the thalassemia is termed +, whereas - 0 thalassemia indicates a complete absence of production of chains from the involved allele. If the synthesis of alpha chain is suppressed, level of the three normal hemoglobin viz. A, A2 & F are reduced (alpha thalassemia). On other hand if beta gene chains are suppressed because of mutations in beta gene then production of adult hemoglobin is suppressed (beta thalassemia). Delta thalassemia is due to suppression of both beta & delta chain synthesis (HbF is high) with moderate anemia. The consequences of impaired production of globin chains ultimately result in the deposition of less Hb into each RBC, leading to hypochromasia. The Hb deficiency causes RBCs to be smaller, leading to the classic hypochromic & microcytic picture of thalassemia. This is true in almost all anemias caused by impairment in production of either of the 2 main components of Hb : heme or globin. However, this does not occur in the silent carrier state, since both Hb level & RBC indices remain normal. In the most common type of thalassemia trait, the level of Hb A2 ( 2/ 2) is usually elevated. This is due to the increased use of chains by the excessive free chains, which results from a lack of adequate chains with which to pair. The gene, unlike and genes, is known to have a physiologic limitation in its ability to produce adequate chains; by pairing with the chains, chains produce Hb A2 (approximately 2.5 - 3% of the total Hb). Some, but not all, of the excessive chains are used to form Hb A2 with the chains, whereas the remaining chains precipitate in the cells, reacting with cell membranes, intervening with normal cell division & acting as foreign bodies, leading to destruction of RBCs. The degree of toxicity caused by the excessive chains varies according to the type of such chains (e.g. the toxicity of chains in thalassemia is more prominent than the toxicity of chains in thalassemia).
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In the severe forms, such as thalassemia major or Cooley anemia, the same pathophysiology applies with substantial exaggeration. The significant excess of free chains caused by the deficiency of chains causes destruction of the RBC precursors in the bone marrow (i.e. ineffective erythropoiesis).
Cellular pathophysiology

The basic defect in all types of thalassemia is imbalanced globin chain synthesis. However, the consequences of accumulation of the excessive globin chains in the various types of thalassemia are different. In thalassemia, excessive chains, unable to form Hb tetramers, precipitate in the RBC precursors and, in one way or another, produce most of the manifestations encountered in all of the thalassemia syndromes; this is not the situation in thalassemia. The excessive chains in thalassemia are chains earlier in life & chains later in life. Because such chains are relatively soluble, they are able to form homotetramers that, although relatively unstable, nevertheless remain viable & able to produce soluble Hb molecules such as Hb Bart (4 chains) & Hb H (4 chains). These basic differences in the 2 main types of thalassemia are responsible for the major differences in their clinical manifestations & severity. chains that accumulate in the RBC precursors are insoluble, precipitate in the cell, interact with the membrane (causing significant damage) & interfere with cell division. This leads to excessive intramedullary destruction of the RBC precursors. In addition, the surviving cells that arrive in the peripheral blood with intracellular inclusion bodies (excess chains) are subject to hemolysis; this means that both hemolysis & ineffective erythropoiesis cause anemia in the person with thalassemia. The ability of some RBCs to maintain the production of chains, which are capable of pairing with some of the excessive chains to produce Hb F, is advantageous. Binding some of the excess a chains undoubtedly reduces the symptoms of the disease & provides additional Hb with oxygen - carrying ability.

Furthermore, increased production of Hb F, in response to severe anemia, adds another mechanism to protect the RBCs in persons with thalassemia. The elevated Hb F level increases oxygen affinity, leading to hypoxia, which, together with the profound anemia, stimulates the production of erythropoietin. As a result, severe expansion of the ineffective erythroid mass leads to severe bone expansion & deformities. Both iron absorption & metabolic rate increase, adding more symptoms to the clinical & laboratory manifestations of the disease. The large numbers of abnormal RBCs processed by the spleen, together with its hematopoietic response to the anemia if untreated, results in massive splenomegaly, leading to manifestations of hypersplenism. If the chronic anemia in these patients is corrected with regular blood transfusions, the severe expansion of the ineffective marrow is reversed. Adding a second source of iron would theoretically result in more harm to the patient. However, this is not the case because iron absorption is regulated by 2 major factors : ineffective erythropoiesis & iron status in the patient. Ineffective erythropoiesis results in increased absorption of iron because of down regulation of the HAMP gene, which produces a liver hormone called hepcidin. Hepcidin regulates dietary iron absorption, plasma iron concentration & tissue iron distribution & is the major regulator of iron. It acts by causing degradation of its receptor, the cellular iron exporter ferroportin. When ferroportin is degraded, it decreases iron flow into the plasma from the gut, from macrophages & from hepatocytes, leading to a low plasma iron concentration. In severe hepcidin deficiency, iron absorption is increased & macrophages are usually iron depleted, such as is observed in patients with thalassemia intermedia. Malfunctions of the hepcidin - ferroportin axis contribute to the etiology of different anemias, such as is seen in thalassemia, anemia of inflammation & chronic renal diseases. Improvement & availability of hepcidin assays facilitates diagnosis of such conditions. The development of hepcidin agonists & antagonists may enhance
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the treatment of such anemias. By administering blood transfusions, the ineffective erythropoiesis is reversed & the hepcidin level is increased; thus, iron absorption is decreased & macrophages retain iron. Iron status is another important factor that influences iron absorption. In patients with iron overload (e.g. hemochromatosis), the iron absorption decreases because of an increased hepcidin level. However, this is not the case in patients with severe thalassemia because a putative plasma factor overrides such mechanisms & prevents the production of hepcidin. Thus, iron absorption continues despite the iron overload status. As mentioned above, the effect of hepcidin on iron recycling is carried through its receptor ferroportin, which exports iron from enterocytes & macrophages to the plasma & exports iron from the placenta to the fetus. Ferroportin is up regulated by iron stores & down regulated by hepcidin. This relationship may also explain why patients with thalassemia who have similar iron loads have different ferritin levels based on whether or not they receive regular blood transfusions. For example, patients with thalassemia intermedia who are not receiving blood transfusions have lower ferritin levels than those with thalassemia major who are receiving regular transfusion regimens, despite a similar iron overload. In the latter group, hepcidin allows recycling of the iron from the macrophages, releasing high amounts of ferritin. In patients with thalassemia intermedia, in whom the macrophages are depleted despite iron overload, lower amounts of ferritin are released, resulting in a lower ferritin level. Most nonheme iron in healthy individuals is bound tightly to its carrier protein, transferrin. In iron overload conditions, such as severe thalassemia, the transferrin becomes saturated & free iron is found in the plasma. This iron is harmful since it provides the material for the production of hydroxyl radicals & additionally accumulates in various organs, such as the heart, endocrine glands & liver, resulting in significant damage to these organs.

By understanding the etiology of the symptoms in thalassemia, one can appreciate that certain modifiers may result in the development of milder types of thalassemia. Factors that may reduce the degree of globin chain imbalance are expected to modify the severity of the symptoms; co - inheritance of thalassemia, the presence of higher Hb F level, or the presence of a milder thalassemia mutation all typically ameliorate the symptoms of thalassemia.
Classification of thalassemia

is frequently adequate evidence for the presence of thalassemia.

thalassemia trait
This trait is characterized by mild anemia & low RBC indices. This condition is typically caused by the deletion of 2 (a) genes on one chromosome 16 (aa/oo) or one from each chromosome (ao/ao). This condition is encountered mainly in Southeast Asia, the Indian subcontinent & some parts of the Middle East. The ao/ao form is much more common in black populations because the doubly deleted (oo) form of chromosome 16 is rare in this ethnic group.
Hb H disease

A large number of thalassemic syndromes are currently known; each involves decreased production of one globin chain or more, which form the different Hbs normally found in RBCs. The most important types in clinical practice are those that affect either or chain synthesis.

(thalassemia intermedia)

thalassemia
Several forms of thalassemia are known in clinical practice. The most common forms are as follows :
Silent carrier thalassemia

This is a fairly common type of subclinical thalassemia, usually found by chance among various ethnic populations, particularly African American, while the child is being evaluated for some other condition. As pointed out above, 2 genes are located on each chromosome 16, giving thalassemia the unique feature of gene duplication. This duplication is in contrast to only one - globin gene on chromosome 11. In the silent carrier state, one of the genes is usually absent, leaving only 3 of 4 genes (aa/ao). Patients are hematologically healthy, except for occasional low RBC indices. In this form, the diagnosis cannot be confirmed based on Hb electrophoresis results, which are usually normal in all thalassemia traits. More sophisticated tests are necessary to confirm the diagnosis. One may look for hematologic abnormalities in family members (e.g. parents) to support the diagnosis. A CBC count in one parent that demonstrates hypochromia & microcytosis in the absence of any explanation
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This condition, which results from the deletion or inactivation of 3 globin genes (oo/ao), represents thalassemia intermedia, with mildly to moderately severe anemia, splenomegaly, icterus & abnormal RBC indices. When peripheral blood films stained with supravital stain or reticulocyte preparations are examined, unique inclusions in the RBCs are usually observed. These inclusions represent b chain tetramers (Hb H), which are unstable & precipitate in the RBC, giving it the appearance of a golf ball. These inclusions are termed Heinz bodies, depicted below.
Supra vital stain in hemoglobin H disease that reveals Heinz bodies (golf ball appearance).

thalassemia major - This condition is the result of complete deletion of the a gene cluster on both copies of chromosome 16 (oo/oo), leading to the severe form of homozygous thalassemia, which is usually incompatible with life & results in hydrops fetalis unless intrauterine blood transfusion is given. thalassemia - Similar to thalassemia, several clinical forms of thalassemia are recognized; some of the more common forms are as follows : Silent carrier thalassemia - Similar to patients who silently carry thalassemia; these patients have no symptoms, except for possible low RBC indices. The mutation that causes the

thalassemia is very mild & represents a + thalassemia. thalassemia trait - Patients have mild anemia, abnormal RBC indices & abnormal Hb electrophoresis results with elevated levels of Hb A 2 , Hb F, or both. Peripheral blood film examination usually reveals marked hypochromia & microcytosis (without the anisocytosis usually encountered in iron deficiency anemia), target cells & faint basophilic stippling, as depicted below. The production of chains from the abnormal allele varies from complete absence to variable degrees of deficiency.

thalassemic disorders. Reportedly, disorders worldwide & people who carry thalassemia in India alone number approximately 30 million. These facts confirm that thalassemias are among the most common genetic disorders in humans; they are encountered among all ethnic groups & in almost every country around the world. Certain types of thalassemia are more common in specific parts of the world
Mortality / Morbidity

Peripheral blood film in thalassemia minor Thalassemia intermedia - This condition is usually due to a

compound heterozygous state, resulting in anemia of intermediate severity, which typically does not require regular blood transfusions. thalassemia associated with chain structural variants - The most significant condition in this group of thalassemic syndromes is the Hb E/ thalassemia, which may vary in its clinical severity from as mild as thalassemia intermedia to as severe as thalassemia major. Thalassemia major (Cooley anemia) - This condition is characterized by transfusion - dependent anemia, massive splenomegaly, bone deformities, growth retardation & peculiar facies in untreated individuals, 80% of whom die within the first 5 years of life from complications of anemia. Examination of a peripheral blood preparation in such patients reveals severe hypochromia & microcytosis, marked anisocytosis, fragmented RBCs, hypochromic macrocytes, polychromasia, nucleated RBCs, and, on occasion, immature leukocytes, as shown below.

Beta thalassemia major is a mortal disease & virtually all affected fetuses are born with hydrops fetalis as a result of severe anemia. Patients with Hb H disease also require close monitoring. They may require frequent or only occasional blood transfusions, depending on the severity of the condition. Some patients may require splenectomy. Morbidity is usually related to the anemia, complications of blood transfusions, massive splenomegaly in some patients, or the complications of splenectomy in others. In patients with various types of ? thalassemia, mortality & morbidity vary according to the severity of the disease & the quality of care provided. Heart failure due to severe anemia or iron overload is a common cause of death in affected persons. Liver disease, fulminating infection, or other complications precipitated by the disease or by its treatment are some of the causes of morbidity & mortality in the severe forms of thalassemia.
Sex

Both sexes are equally affected with thalassemia.

Age

Peripheral blood film in Cooley anemia Frequency International

Despite the inherited nature of thalassemia, age at onset of symptoms varies significantly. In beta thalassemia, clinical abnormalities in patients with severe cases & hematologic findings in carriers are evident at birth. Unexplained hypochromia & microcytosis in a neonate, depicted below, are highly suggestive of the diagnosis.
Peripheral blood film in hemoglobin H disease in a newborn
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Worldwide, 15 million people have clinically apparent

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History

The history in patients with thalassemia widely varies, depending on the severity of the condition & the age at the time of diagnosis. In most patients with thalassemia traits, no unusual signs or symptoms are encountered. Some patients, especially those with somewhat more severe forms of the disease, manifest some pallor & slight icteric discoloration of the sclerae with splenomegaly, leading to slight enlargement of the abdomen. An affected childs parents or caregivers may report these symptoms. The diagnosis is usually suspected in children with an unexplained hypochromic & microcytic picture, especially those who belong to one of the ethnic groups at risk. For this reason, physicians should always inquire about the patients ethnic background, family history of hematologic disorders & dietary history. Thalassemia should be considered in any child with hypochromic microcytic anemia that does not respond to iron supplementation. In more severe forms, such as beta thalassemia major, the symptoms vary from extremely debilitating in patients who are not receiving transfusions to mild & almost asymptomatic in those receiving regular transfusion regimens & closely monitored chelation therapy. Manifestations of anemia include extreme pallor & enlarged abdomen due to hepatosplenomegaly. o Patients typical reports may lead a physician who is not familiar with the condition to a first impression of acute leukemia. o This impression is supported by the large spleen, which leads to thrombocytopenia & by the high WBC count & immature WBCs seen on the peripheral blood film due to the extreme
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activity of the marrow. To support the impression of acute leukemia further, the elevated level of reticulocytes expected in all hemolytic anemias does not occur, despite the severe hemolysis; this anomaly is due to the massive splenomegaly & the ineffective erythropoiesis that prevents the release of the cells from the bone marrow. Evidence of hemolysis is usually present, with elevated indirect bilirubin level, high lactate dehydrogenase (LDH) level & low level of haptoglobin. Bony changes may be severe, resulting in a characteristic radiologic picture (see Imaging Studies & the image below). These changes are caused by massive expansion of the bone due to the ineffective erythroid production.

The classic hair on end appearance on plain skull radiographs of a patient with Cooley anemia.

The ineffective erythropoiesis also creates a state of hypermetabolism associated with fever & failure to thrive. Occasionally, gout due to hyperuricemia may be encountered. Iron overload is one of the major causes of morbidity in all patients with severe forms of thalassemia, regardless of whether they are regularly transfused. In transfused patients, heavy iron turnover from transfused blood is usually the cause; in nontransfused patients, this complication is usually deferred until puberty (if the patient survives to that age). Increased iron absorption is the cause in nontransfused patients, but the reason behind this phenomenon is not clear. Many believe that, despite the iron overload state in these patients & the increased iron deposits in the bone marrow, the requirement for iron to supply the overwhelming production of ineffective erythrocytes is tremendous, causing significant increases in GI absorption of iron. Bleeding tendency, increased susceptibility to infection & organ dysfunction are all associated with iron overload.

Poor growth in patients with thalassemia is due to multiple factors & affects patients with well - controlled disease as well as those with uncontrolled disease. Patients may develop symptoms that suggest diabetes, thyroid disorder, or other endocrinopathy; these are rarely the presenting reports.

overload may also demonstrate signs of endocrinopathy caused by iron deposits. Diabetes & thyroid or adrenal disorders have been described in these patients. In patients with severe anemia who are not receiving transfusion therapy, neuropathy or paralysis may result from compression of the spine or peripheral nerves by large extramedullary hematopoietic masses.
Causes

Physical

Patients with thalassemia minor rarely demonstrate any physical abnormalities. Because the anemia is never severe and, in most instances, the Hb level is not less than 9 - 10 g/dL, pallor & splenomegaly are rarely observed. In patients with severe forms of thalassemia, the findings upon physical examination widely vary, depending on how well the disease is controlled. Findings include the following : Children who are not receiving transfusions have a physical appearance so characteristic that an expert examiner can often make a spot diagnosis. In Cooleys original 4 patients, the stigmata of severe untreated beta thalassemia major included the following : o Severe anemia, with an Hb level of 3 - 7g/dL o Massive hepatosplenomegaly o Severe growth retardation o Bony deformities These stigmata are typically not observed; instead, patients look healthy. Any complication they develop is usually due to adverse effects of the treatment (transfusion or chelation). Bony abnormalities, such as frontal bossing, prominent facial bones & dental malocclusion, are usually striking. Severe pallor, slight to moderately severe jaundice & marked hepatosplenomegaly are almost always present. Complications of severe anemia are manifested as intolerance to exercise, heart murmur, or even signs of heart failure. Growth retardation is a common finding, even in patients whose disease is well controlled by chelation therapy. Patients with signs of iron
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Thalassemias are inherited disorders caused by various gene mutations. The clinical expression & severity are subject to numerous factors that may either mask the condition or exaggerate the symptoms, leading to a more severe disease.
Differential Diagnoses

Anemia, Acute Anemia, Chronic Hydrops Fetalis Pyruvate Kinase Deficiency Thalassemia Intermedia
Laboratory Studies

o o

o o

Laboratory studies in thalassemia include the following The CBC count & peripheral blood film examination results are usually sufficient to suspect the diagnosis. Hemoglobin (Hb) evaluation confirms the diagnosis. In the severe forms of thalassemia, the Hb level ranges from 2 - 8 g/dL. Mean corpuscular volume (MCV) & mean corpuscular Hb (MCH) are significantly low, but, unlike thalassemia trait, thalassemia major is associated with a markedly elevated RDW, reflecting the extreme anisocytosis. The WBC count is usually elevated in beta thalassemia major; this is due, in part, to miscounting the many nucleated RBCs as leukocytes. Leukocytosis is usually present, even after excluding the nucleated RBCs. A shift to the left is also encountered, reflecting the hemolytic process. Platelet count is usually normal, unless the spleen is markedly enlarged. Peripheral blood film examination reveals marked hypochromasia & microcytosis, hypochromic macrocytes that

represent the polychromatophilic cells, nucleated RBCs, basophilic stippling & occasional immature leukocytes.
Iron studies are as follows :

Serum iron level is elevated, with saturation reaching as high as 80%. The serum ferritin level, which is frequently used to monitor the status of iron overload, is also elevated. However, an assessment using serum ferritin levels may underestimate the iron concentration in the liver of a transfusion - independent patient with thalassemia. Complete RBC phenotype, hepatitis screen, folic acid level & human leukocyte antigen (HLA) typing are recommended before initiation of blood transfusion therapy.

Imaging Studies

Skeletal survey & other imaging studies reveal classic changes of the bones that are usually encountered in patients who are not regularly transfused. The striking expansion of the erythroid marrow widens the marrow spaces, thinning the cortex & causing osteoporosis. These changes, which result from the expanding marrow spaces, usually disappear when marrow activity is halted by regular transfusions. Osteoporosis & osteopenia may cause fractures, even in patients whose conditions are well - controlled. In addition to the classic hair on end appearance of the skull, shown below, which results from widening of the diploic spaces & observed on plain radiographs, the maxilla may overgrow, which results in maxillary overbite, prominence of the upper incisors & separation of the orbit. These changes contribute to the classic chipmunk facies observed in patients with thalassemia major
The classic hair on end appearance on plain skull radiographs of a patient with Cooley anemia.

Other bony structures, such as ribs, long bones & flat bones, may also be sites of major deformities. Plain radiographs of the long bones may reveal a lacy trabecular pattern. Changes in the pelvis, skull & spine become more evident during the second decade of life, when the marrow in the peripheral bones becomes inactive while more activity occurs in the central bones. Compression fractures & paravertebral expansion of extramedullary masses, which could behave clinically like tumors, more frequently occur during the second decade of life. MRI & CT scanning are usually used in diagnosing such complications. Chest radiography is used to evaluate cardiac size & shape. MRI & CT scanning can be used as noninvasive means to evaluate the amount of iron in the liver in patients receiving chelation therapy. A newer noninvasive procedure involves measuring the cardiac T2 with cardiac magnetic resonance (CMR). This procedure has shown decreased values in cardiac T2 due to iron deposit in the heart. Unlike liver MRI, which usually correlates very well with the iron concentration in the liver measured using percutaneous liver biopsy samples & the serum ferritin level, CMR does not correlate well with the ferritin level, the liver iron level, or echocardiography findings. This suggests that cardiac iron overload cannot be estimated with these surrogate measurements. This is also true in measuring the response to chelation therapy in patients with iron overload. The liver is clear of iron loading much earlier than the heart, which also suggests that deciding when to stop or reduce treatment based on liver iron levels is misleading. Hepatic iron content (HIC) obtained by liver biopsy, cardiac function tests obtained by echocardiography measurements & multiple gated acquisition scan (MUGA) findings were compared to the results of iron measurements on R2 - MRI in the liver & heart. Various iron overload patients were involved in the study that revealed that R2 MRI was strongly associated with HIC (weakly but significantly with ferritin level) & represents an excellent noninvasive method to
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evaluate iron overload in the liver & heart & to monitor response to chelation therapy.
Other Tests

The following tests may be indicated : ECG & echocardiography are performed to monitor cardiac function. HLA typing is performed for patients for whom bone marrow transplantation is considered. Eye examinations, hearing tests, renal function tests & frequent blood counts are required to monitor the effects of deferoxamine (DFO) therapy & the administration of other chelating agents (see Treatment, Medication).

Procedures

Bone marrow aspiration is needed in certain patients at the time of the initial diagnosis to exclude other conditions that may manifest as thalassemia major. Liver biopsy is used to assess iron deposition & the degree of hemochromatosis. Measurement of urinary excretion of iron after a challenge test of DFO is used to evaluate the need to initiate chelation therapy & reflects the amount of iron overload.
Histologic Findings

individual is reached. Counseling is indicated in all persons with genetic disorders, especially when the family is at risk of a severe form of disease that may be prevented. Patients with severe thalassemia require medical treatment & a blood transfusion regimen was the first measure effective in prolonging life. In the process of experimenting with blood transfusion, it was found to provide patients with many benefits, including reversal of the complications of anemia, elimination of ineffective erythropoiesis & its complications, allowance of normal or near - normal growth & development & extension of patients life spans. Blood transfusion should be initiated at an early age when the child is symptomatic & after an initial period of observation to assess whether the child can maintain an acceptable level of Hb without transfusion. Accumulation of transfused iron & its consequences also needed to be monitored. Chelation therapy was considered after extensive research & many clinical trials. Today, regular blood transfusion combined with well - monitored chelation therapy has become the standard therapy & has drastically changed the outlook for this population of patients.
Blood transfusions

All severe forms of thalassemia exhibit hyperactive marrow with erythroid hyperplasia & increased iron stores in marrow, liver & other organs. In the untreated person with severe disease, extramedullary hematopoiesis in unusual anatomic sites is one of the known complications. Erythroid hyperplasia is observed in bone marrow specimens. Increased iron deposition is usually present in marrow, as depicted in the image below, liver, heart & other tissues.
Medical Care

Patients with thalassemia traits do not require medical or follow - up care after the initial diagnosis is made. Iron therapy should not be used unless a definite deficiency is confirmed & should be discontinued as soon as the potential hemoglobin (Hb) level for that

Several blood transfusion regimens have been introduced. Of these, one seems practical, less demanding & more cost effective than any of the others. This regimen attempts to maintain a pretransfusion Hb level of 9 - 9.5 g/dL at all times. Like all patients who require long - term regular blood transfusions, patients with thalassemia require a pretransfusion workup. This workup should include RBC phenotype, hepatitis B vaccination (if needed) & hepatitis workup. Iron & folate levels should also be measured. Transfused blood should always be leukocyte poor; 10 - 15 mL/kg packed RBCs (PRBCs) at the rate of 5 mL/kg/h every 3 - 5 weeks is usually adequate to maintain the pretransfusion Hb level needed.

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Consider administration of acetaminophen & diphenhydramine hydrochloride before each transfusion to minimize febrile or allergic reactions. Patients with documented transfusion reactions may benefit from having RBCs washed with saline or from receiving deglycerolized RBCs.

Complications of blood transfusion

The major complications of blood transfusions are those related to transmission of infectious agents or the development of iron overload.
Iron overload

Even though blood transfusion is supposed to decrease the excessive iron absorption in the GI tracts of patients with thalassemia, patients nevertheless receive large amounts of iron with each blood transfusion. Why patients with excessive iron absorb large amounts of iron from the GI tract is not clear. As iron accumulates & exceeds body needs, production of apoferritin is accelerated to provide means for storing iron in nontoxic forms as ferritin or hemosiderin. Measuring the ferritin level in the first few years after the diagnosis of thalassemia is usually helpful in detecting iron overload status because ferritin correlates well with total body iron burden at this time. Until recently, patients with thalassemia major who received only transfusion therapy could not survive beyond adolescence, largely because of cardiac complications caused by iron toxicity. The introduction of chelating agents capable of removing excessive iron from the body has dramatically increased life expectancy. When administered in conjunction with blood transfusion regimens, chelation can delay the onset of cardiac disease and, in some patients, even prevent its occurrence. Several chelating agents have been tested, and, although many failed, one particular agent was proven effective & safe. DFO
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Chelation therapy

is a complex hydroxylamine with high affinity for iron; it targets the labile pool, the nontransferrin - bound iron (free pool) & the ferritin generated from reticuloendothelial iron. Because the agent is not absorbed in the gut, it must be administered parenterally, whether intramuscularly, intravenously, or subcutaneously. Because of its short half life, subcutaneous infusion must be prolonged if it is to achieve the stated goal. A total dose of 30 - 40 mg/kg/d is infused over 8 - 12 hours during the childs sleep for 5 d/wk by a mechanical pump. Oral chelating agents have been in use in other countries for some time & newer ones are showing efficacy & some specificity for removing iron more efficiently from certain organs than DFO. Deferasirox is a relatively new oral chelating agent with a long half - life, for this reason it is administered orally once daily. Several studies in the last few years have shown that this agent is as effective as its predecessor, deferoxamine, in reducing ferritin level & tissue iron accumulation. Vitamin E deficiency - Vitamin E deficiency has been reported in patients with severe thalassemia. Some of the hemolysis in this population was attributed to peroxidation of the RBC membrane lipids by an iron - mediated free radical effect. As an antioxidant, vitamin E is expected to decrease cell toxicity. Folic acid deficiency - This deficiency is a common complication in patients with thalassemia, mainly because of the extreme demand associated with the severe expansion of the marrow. For this reason, folic acid (1 mg/d) has been recommended as a supplement for this patient population. Gene therapy - This therapy is an attractive therapeutic modality, the efficacy of which remains to be demonstrated. It means transfer of normal gene in stem cells to correct the underlying defect.

Surgical Care

Splenectomy is the principal surgical procedure used for many patients with thalassemia. The spleen is known to contain a large amount of the labile nontoxic iron (i.e. storage function) derived from sequestration of the released iron. The spleen also increases RBC destruction & iron distribution (i.e. scavenger function). These facts should always be considered before the decision is made to proceed with splenectomy. In addition, with recent reports of venous thromboembolic events (VTEs) after splenectomy, one should carefully consider the benefits & the risks before splenectomy is advocated. The spleen acts as a store for nontoxic iron, thereby protecting the rest of the body from this iron. Early removal of the spleen may be harmful (liver cirrhosis has occurred in such individuals). Another surgical procedure in patients with severe thalassemia on transfusion therapy is the placement of a central line for the ease & convenience of administering blood transfusions, chelation therapy, or both.
Diet

Deferasirox

Tab for PO susp. PO iron chelation agent demonstrated to reduce liver iron concentration in adults & children who receive repeated RBC transfusions. Binds iron with high affinity in a 2 :1 ratio. Approved to treat chronic iron overload due to multiple blood transfusions. Treatment initiation recommended with evidence of chronic iron overload (i.e. transfusion of about 100 mL/kg packed RBCs [about 20 U for patient weighing 40 kg] & serum ferritin level consistently > 1000 mcg/L). < 2 years - Not established > 2 years - Administer as in adults
Ascorbic acid

Delays conversion of transferrin to hemosiderin, thus making iron more accessible to chelation. 3 mg/kg/d PO administered with SC deferoxamine infusion
Alpha - tocopherol

A normal diet is recommended, with emphasis on the following supplements : folic acid, small doses of ascorbic acid (vitamin C) & alpha - tocopherol (vitamin E). Iron should not be given & foods rich in iron should be avoided. Drinking coffee or tea has been shown to help decrease absorption of iron in the gut.
Activity

An antioxidant. Prevents iron - mediated toxicity caused by peroxidation of cell membrane lipids, reducing extent of accompanying hemolysis. Protects polyunsaturated fatty acids in membranes from attack by free radicals & protects RBCs against hemolysis. Demonstrated to be deficient in patients with iron overload receiving chelation therapy. 1 IU/kg/d PO
Folic acid

Patients with well - controlled disease are usually fully active. Patients with anemia, heart failure, or massive hepatosplenomegaly are usually restricted according to their tolerances.
Deferoxamine mesylate

Required for DNA synthesis; therefore in great demand in these patients because of increased cellular turnover. Deficient in most patients with chronic hemolysis. 1 mg/d PO
Hydroxyurea

Chelates iron from ferritin or hemosiderin but not from transferrin, cytochrome, or Hb. 20 - 40 mg/kg/d SC infusions through infusion pump over 8 12 h. After blood transfusion : 1 - 2 g IV at slow rate of 15 mg/kg/h
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Inhibitor of deoxynucleotide synthesis. 15 mg/kg/d PO (range 10 - 20 mg/kg/d) initially; may increase by increments of 5 mg//kg/d q12wk; not to exceed 35 mg/kg/d Excessive chelation with deferoxamine may cause growth

retardation. Growth hormone may be effective in increasing growth rate in all thalassemic patient particularly the ones with growth hormone deficiency.
Somatropin

1) 2)

Treatment with insulin is necessary Increased tendency of DKA Family history present in 10% Genetic - The etiology of type 1 DM has a strong genetic component. Environmental - These factors may act as modifiers of disease rather than triggers. Environmental agents that have been believed to induce an attack & infect beta cell function include viruses (e.g., mumps, rubella, Coxsackie B4), toxic chemicals, seasonal changes & cytotoxins. Dietary - Early introduction of cow milk may be associated Autoimmunity - Type 1 DM may result due to autoimmune destruction of the beta cells.
Pathogenesis

Causes

Human growth hormone produced by recombinant DNA technology (mouse C127 cell line). Elicits anabolic & anti - catabolic influence on various cells including : myocytes, hepatocytes, adipocytes, lymphocytes & hematopoietic cells. Exerts activity on specific cell receptors including insulinlike growth factor - 1 (IGF 1). 0.18 - 0.3 mg/kg/wk SC divided into 6 - 7 injections; not to exceed 0.7 mg/kg/wk during puberty Depot : 1.5 mg/kg/month or 0.75 mg/kg SC q2wk

3) 4)

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Diabetes millitus

Types 1) 2)

Environmental insults (viral infections) Activation of immunological t & b lymphocytes Inflammatory reaction Auto antibodies against islet cells (autoimmune reaction) Destruction of islet/beta cells
IDDM

Type 1 (IDDM / juvenile diabetes) Type 2 (NIDDM)

Genetic predisposition & environmental factors lead to initiation of a autoimmune process against pancreatic islets.
Phase 1 phase of clinical symptoms

This leads to progressive destruction of b cells. At onset of clinical diabetes 80 90 % of islet cells are destroyed. It includes
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In type 1 diabetes, there is low or absent endogenously produced insulin. Caused due to autoimmune destruction of pancreatic islet cell Onset is acute Irreversible beta cell damage is present. Autoimmunity is t cell mediated. Occurs most commonly in childhood with average age 7 to 15 yrs, but can occur in adults, especially in those in their late 30s & early 40s.

Diabetes millitus (DM) is a multisystem, endocrinal disease with both biochemical & anatomical consequences. It is a chronic disease of carbohydrate, fat & protein metabolism caused by the lack of insulin.

Genetic predisposition

polyuria, polyphagia, nocturia, recent weight loss & fatigue.

Phase 2 honeymoon phase (remission phase)

ketogenesis) Excessive lypolysis, amino acids Ketone body formation (acetone, acetoacetic acid) (Metabolic acidosis) DKA Compensatory rapid deep breathing (hyperventilation) to excrete more co2 (kussmaul breathing) Fruity odor to breath (acetone) Ketonuria further dehydration, cerebral O2 Leads to impaired consciousness COMA

Regeneration of new is lets. Transient decrease in insulin requirements associated with improved b cell function.
Phase 3 relapse

This results from declining endogenous insulin secretion & insulin resistance.
Phase 4 stage of total diabetes

Complete beta cell destruction with no capacity for endogenous insulin synthesis or relapse. It is a irreversible state. Unlike people with type 2 DM, those with type 1 DM generally are not obese & may present initially with diabetic ketoacidosis (DKA).
Pathophysiology Insulin (Insulin promotes glucose uptake from blood)

Utilization of glucose by muscles Post prandial hyperglycemia

Glycosuria (when renal threshold exceeds > 180mg/dl)

Osmotic diuresis
Polyuria Dehydration (loss of water & electrolytes) polydipsia Physiologic (stress leads to release of stress hormones)

1) 2) 3)

Epinephrine (impair insulin secretion) Cortisol, gh (antagonize insulin action) Cortisol, glucagon (glycogenolysis, gluconeogenesis, lypolysis,
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Type 1 DM is a catabolic disorder in which circulating insulin is very low or absent, plasma glucagon is elevated & the pancreatic beta cells fail to respond to all insulin - secretory stimuli. Patients need exogenous insulin to reverse this catabolic condition, prevent ketosis, decrease hyperglucagonemia & normalize lipid & protein metabolism. The pancreas shows lymphocytic infiltration & destruction of insulin - secreting cells of the islets of Langerhans, causing insulin deficiency. Approximately 85% of patients have circulating islet cell antibodies & the majority also has detectable anti - insulin antibodies before receiving insulin therapy. Most islet cell antibodies are directed against glutamic acid decarboxylase (GAD) within pancreatic B cells. One theory regarding the etiology of type 1 DM is that it results from damage to pancreatic beta cells from an infectious or environmental agent. It triggers the immune system in a genetically susceptible individual to develop an autoimmune response against altered pancreatic beta cell antigens or molecules in beta cells that

resemble a viral protein. Currently, autoimmunity is considered the major factor in the pathophysiology of type 1 DM. Prevalence is increased in patients with other autoimmune diseases, such as Gravess disease, Hashimoto thyroiditis & Addison disease. Approximately 95% of patients with type 1 DM have either human leukocyte antigen (HLA) - DR3 or HLA - DR4. HLA DQs are considered specific markers of type 1 DM susceptibility.

Clinical manifestations Classical triad polyuria, polydipsia, polyphagia,

Other signs are weight loss, lassitude, nausea & blurred vision. Polyuria : Polyuria is due to osmotic diuresis secondary to hyperglycemia. Polydipsia Thirst is due to the hyperosmolar state & dehydration. Polyphagia with weight loss : The weight loss with a normal or increased appetite is due to depletion of water & calories due to a catabolic state with reduced glycogen, proteins & triglycerides. Fatigue & weakness : This may be due to muscle wasting from the catabolic state of insulin deficiency, hypovolemia & hypokalemia. Kussmaul breathing deep & rapid respiration Muscle cramps : This is due to electrolyte imbalance. Nocturnal enuresis : Severe enuresis secondary to polyuria can be an indication of onset of diabetes in young children. Blurred vision : This also is due to the effect of the hyperosmolar state on the lens & vitreous humor. Glucose & its metabolites cause dilation of the lens, altering its normal focal length. Gastrointestinal symptoms : Nausea, abdominal discomfort or pain & change in bowel movements may accompany acute DKA. Acute fatty liver may lead to distention of the hepatic
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capsule, causing right upper quadrant pain. Persistent abdominal pain may indicate another serious abdominal cause of DKA, e.g. pancreatitis. Chronic gastrointestinal symptoms in the later stage of diabetes are due to visceral autonomic neuropathy. Patients may maintain their normal weight or exhibit wasting, depending on the interval between the onset of the disease & initiation of treatment. Peripheral neuropathy : This presents as numbness & tingling in both hands & feet, in a glove & stocking pattern. It is bilateral, symmetric & ascending neuropathy, which results from many factors, including the accumulation of sorbitol in peripheral sensory nerves due to sustained hyperglycemia. Symptoms at the time of the first clinical presentation can usually be traced back several days to several weeks; however, beta cell destruction may have started months, or even years, before the onset of clinical symptoms.

Physical

In new cases of diabetes, physical examination findings are usually normal, except in DKA, wherein signs of Kussmaul respiration, dehydration, hypotension, and, in some cases, altered mental status are present. In established cases, patients should be examined every 3 months for macrovascular & microvascular complications. They should have funduscopic examination for retinopathy & monofilament testing for peripheral neuropathy.
2) Type 2 (NIDDM)

Polygenic disease aggravated by environmental factors, low physical activity or hyper caloric diet Obese adults over 30 yrs of age Obesity is associated with insulin resistance but diabetes does not develop until some degrees of insulin secretion failure. In type 2 dm patient does not require insulin for survival but for better glycemic control.

Genetics

There is also a strong inheritable genetic connection in type 2 diabetes : having relatives (especially first degree) with type 2 increases risks of developing type 2 diabetes very substantially. About 55 percent of type 2 patients are obese at diagnosis. Chronic obesity leads to increased insulin resistance that can develop into Type 2, most likely because adipose tissue (especially that in the abdomen around internal organs) is a (recently identified) source of several chemical signals to other tissues (hormones & cytokines). Insulin resistance means that body cells do not respond appropriately when insulin is present. Unlike type 1 diabetes mellitus, insulin resistance is generally post - receptor, meaning it is a problem with the cells that respond to insulin rather than a problem with the production of insulin. This is a more complex problem than type 1, but is sometimes easier to treat, especially in the early years when insulin is often still being produced internally. Severe complications can result from improperly managed type 2 diabetes, including renal failure, erectile dysfunction, blindness, slow healing wounds (including surgical incisions) & arterial disease, including coronary artery disease. The onset of type 2 has been most common in middle age & later life, although it is being more frequently seen in adolescents & young adults due to an increase in child obesity & inactivity. Diabetes mellitus with a known etiology, such as secondary to other diseases, known gene defects, trauma or surgery, or the effects of drugs, is more appropriately called secondary diabetes mellitus or diabetes due to a specific cause. Examples include diabetes mellitus such as MODY or those caused by hemochromatosis, pancreatic insufficiencies, or certain types of medications (e.g., long - term steroid use). Type 2 diabetes can causes obesity as an effect of the changes in metabolism & other deranged cell behavior attendant on insulin resistance.
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However, environmental factors (almost certainly diet & weight) play a large part in the development of Type 2 in addition to any genetic component There is a stronger inheritance pattern for type 2 diabetes. Those with first - degree relatives with type 2 have a much higher risk of developing type 2, increasing with the number of those relatives.
Mode of NIDDM

1) 2) 3)

Insulin resistance of skeletal muscles Increased hepatic glucose production Decreased glucose induced insulin production. Overweight child (BMI above 85th percentile) Family history in 1st or 2nd degree relative Signs of insulin resistance (acanthosis nigricans, HTN, dyslipedemia, PCOD) Maturity - onset diabetes of youth (MODY), a rare autosomal dominant condition found increasingly in adolescents, but this is classified as a diabetes due to a specific cause & not as type 2 diabetes. Secondary hyperglycemia Disorders of target tissues (liver, muscles, adipose tissue) Endocrine disorders - Endocrine tumor causing increased production of growth hormone, glucocorticoids, catecholamines, glucagon & somatostatin; Addison disease; Graves disease; Hashimoto thyroiditis; acanthosis nigricans (genetic disorders with insulin resistance) Drugs - Thiazide diuretics, phenytoin, glucocorticoids Chronic pancreatitis Cystic fibrosis Prader - Willi syndrome - Mental retardation, muscular hypotonia, obesity, short stature & hypogonadism associated with diabetes mellitus (DM) Nondiabetic glycosuria

Diagnosis

Other Problems to Be Considered

Renal glycosuria - Glucose appears in urine despite normal glucose concentration in blood. This glucose may be due to an autosomal genetic disorder or dysfunction of the proximal renal tubule (e.g. Fanconi syndrome, chronic renal failure), or it may be due to increased glucose load on tubules by the elevated glucose filtration rate during pregnancy. Peripheral neuropathy due to alcohol & vitamin B - 12 deficiency Blood glucose : random blood sugar = 200mg/dl on two separate occasions. Fasting blood sugar = 126mg/dl Serum electrolytes Urinalysis for glucose, ketones & protein : Urine ketones are not reliable for diagnosing or monitoring DKA. Rather, the plasma acetone, and, specifically, the beta - hydroxybutyrate level, is a reliable indicator of DKA. White blood cell count & blood & urine cultures to rule out infection Glycosylated hemoglobin (Hb) or Hb A1c Hb A1c is the stable product of nonenzymatic irreversible glycosylation of the beta chain of Hb by plasma glucose & is formed at rates that increase with increasing plasma glucose levels. Glycated hemoglobin predicts the progression of diabetic microvascular complications. The reference range for nondiabetic people is 6% in most laboratories. Oral glucose tolerance test (OGTT) with insulin levels : Although this test is usually considered unnecessary to make the diagnosis in type 1 DM, with the dramatic increase of type 2 diabetes in the young population, assessment of insulin secretion may become more important. To determine whether the individual has type 1 rather than type 2 DM, an insulin and/or C - peptide level below 5 U/mL, or 0.6 ng/mL, suggests type 1.
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C - peptide is formed during conversion of proinsulin to insulin. A high positive titre of glutamic acid decarboxylase antibodies also suggests type 1 DM. Islet cell antibodies Thyroxine (T4) & thyroid antibodies

Other Tests

Laboratory Studies

Intravenous glucose test for possible early detection of subclinical diabetes HLA typing may be considered. Medical Care - 4 principles should be followed 1) Management of DKA 2) Metabolic control 3) Parenteral education 4) Control of intermittent & long term complications Type 1 diabetes mellitus (DM) patients require insulin therapy to control initial hyperglycemia & maintain serum electrolytes & hydration. At times, the first incidence of ketoacidosis is followed by a symptom - free period during which patients do not need treatment. This honeymoon period follows the initial treatment, in which the disease remits & the patient requires little or no insulin. This remission is due to a partial return of endogenous insulin, which may last for several weeks or months (and sometimes 1 - 2 y). Ultimately, however, the disease recurs & patients require insulin therapy.
Insulin therapy

Insulin injected subcutaneously is the first - line therapy in the treatment of type 1 diabetes. The different types of insulin are based upon their times of onset & durations of action. Short, intermediate & long - acting insulins are available. Regular, lispro & aspart insulins are the only types that can be administered intravenously. Human insulin is less antigenic than previously used animal derived varieties. Rapid - acting insulins include regular insulin, lispro & aspart insulin.

Regular insulin is a preparation of zinc insulin crystals in solution. Its onset of action is 0.5 - 1 h, it peaks at 2.5 - 5 h & duration of action is 6 - 8 h. Lispro insulin is a form of regular insulin that is genetically engineered with the reversal of the amino acids lysine & proline in the B chain. Aspart insulin has aspartic acid substituted for proline in position 28 of the B chain. Both of these insulins are absorbed more quickly & have a rapid onset (5 - 10 min), peak (1 h) & duration (4 h) of action. Therefore, they have the advantage that they may be administered shortly before eating. Intermediate - acting insulins include neutral protamine Hagedorn (NPH) insulin, which contains a mixture of regular & protamine zinc insulin & lente insulin, which contains 30% semilente insulin & 70% ultralente insulin in an acetate buffer. Long - acting insulins include ultralente insulin, containing large zinc insulin crystals in an acetate buffer & insulin glargine, a newer long - acting insulin that has no peak & produces a relatively stable level lasting more than 24 hours. Both insulins can supply basal 24 - hour insulin with a single daily injection.

or dehydration may be started on 0.5 - 0.7 U/kg of intermediate - acting insulin & subcutaneous injections of 0.1 U/kg of regular insulin at 4 - to 6 - hour intervals.
Insulin schedules

Rapid, short & intermediate acting insulins

Multiple subcutaneous insulin injections are administered to control hyperglycemia after meals & to maintain normal plasma glucose levels throughout the day. This may increase the risks of hypoglycemia. Therefore, patients should be well educated about their disease & about self - monitoring of plasma glucose levels. About 25% of the total daily dose is administered as intermediate - acting insulin at bedtime, with additional doses of rapid - acting insulin before each meal (4 - dose regimen). These patients may need additional intermediate - or long acting insulin in the morning for all - day coverage. Patients should adjust their daily dosage based on their self - monitoring of glucoses before each meal & at bedtime. Continuous subcutaneous insulin infusion : This intensive insulin treatment uses a small battery - operated infusion pump that administers a continuous subcutaneous infusion of rapid acting insulin.

Rapid - & short - acting insulins have the most rapid onsets of action & are used whenever quick glucose utilization is needed (e.g., before meals, when blood glucose > 250 mg/dL). They stimulate proper utilization of glucose by the cells & reduce blood sugar levels. Intermediate - acting insulins have slower onsets of action & longer durations of action & are usually administered in combination with faster - acting insulins to maximize benefits of a single injection.
Initiation of insulin therapy in children

Consultations

These patients should be referred to an endocrinologist for multidisciplinary management. These patients should have a complete retinal examination by an ophthalmologist at least once a year. The patients with significant proteinuria or a reduced creatinine clearance should be referred to a nephrologist.
Diet

Children with moderate hyperglycemia but without ketonuria or acidosis may be started with a single daily subcutaneous injection of 0.3 - 0.5 U/kg of intermediate - acting insulin alone. Children with hyperglycemia & ketonuria but without acidosis
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One of the first steps in managing type 1 DM is diet control. Diet recommendations should be made in view of the patients eating habits & lifestyle. Balanced diet should be advised Diet management includes education about the timing, size,

frequency, or composition of meals to avoid hypoglycemia or postprandial hyperglycemia. All patients on insulin should receive a comprehensive diet plan that includes a daily caloric intake prescription; recommendations for amounts of dietary carbohydrate, fat & protein; & how to divide calories between meals & snacks. In these patients, the caloric distribution is important; a recommended distribution consists of 20% of daily calories for breakfast, 35% for lunch, 30% for dinner & 15% for late evening snack. The minimum protein requirement for good nutrition is 0.9 g/ kg/d (range = 1 - 1.5 g/kg/d), but a reduced protein intake is indicated in cases of nephropathy. Fat intake should be limited to 30% or less of the total calories & a low - cholesterol diet is recommended. Patients should consume sucrose in moderation & increase their fiber intake. In some cases, midmorning & mid afternoon snacks are important to avoid hypoglycemia.

mEq/L or less.
Pathophysiology

Activity

Exercise is an important aspect of diabetes management. Patients should be encouraged to exercise regularly. This promotes glucose utilization & increases sensitivity of muscles to insulin.
Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is an acute, major, life threatening complication of diabetes. DKA mainly occurs in patients with type 1 diabetes, but it is not uncommon in some patients with type 2 diabetes. DKA clinically is defined as an acute state of severe uncontrolled diabetes that requires emergency treatment with insulin & intravenous fluids. Biochemically, DKA is defined as an increase in the serum concentration of ketones greater than 5 mEq/L, a blood glucose level of greater than 250 mg/dL (although it is usually much higher), blood pH of less than 7.2 & a bicarbonate level of 18
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Diabetic ketoacidosis (DKA) is a complex disordered metabolic state characterized by hyperglycemia, acidosis & ketonuria. DKA usually occurs as a consequence of absolute or relative insulin deficiency that is accompanied by an increase in counter - regulatory stress hormones (i.e. glucagon, cortisol, growth hormone & epinephrine). This type of hormonal imbalance enhances hepatic gluconeogenesis, glycogenolysis & lipolysis. Hepatic gluconeogenesis, glycogenolysis secondary to insulin deficiency & counter - regulatory hormone excess result in severe hyperglycemia; while lipolysis increases serum free fatty acids. Hepatic metabolism of free fatty acids as an alternative energy source (i.e. ketogenesis) results in accumulation of acidic intermediate & end metabolites (i.e. ketones, ketoacids). Ketones include acetone, beta hydroxybutyrate & acetoacetate. Progressive rise of blood concentration of these acidic organic substances initially leads to a state of ketonemia. Natural body buffers can buffer ketonemia in its early stages. When the accumulated ketones exceed the bodys capacity of extracting them, they overflow into urine (i.e. ketonuria) If not treated promptly, more accumulation of organic acids leads to frank clinical metabolic acidosis (i.e. ketoacidosis), with a drop in pH & bicarbonate serum levels. Respiratory compensation of this acidotic condition results in rapid shallow breathing (Kussmaul respiration). Ketones, in particular beta hydroxybutyrate, induce nausea & vomiting that consequently aggravate fluid & electrolyte loss already existing in DKA. Moreover, acetone produces the characteristic fruity breath odor of ketotic patients. Hyperglycemia usually exceeds the renal threshold of glucose

Age

absorption & results in significant glycosuria. Consequently, water loss in the urine is increased due to osmotic diuresis induced by glycosuria. This incidence of increased water loss results in severe dehydration, thirst, tissue hypoperfusion, and, possibly, lactic acidosis. Hyperglycemia, osmotic diuresis, serum hyperosmolarity & metabolic acidosis result in severe electrolyte disturbances. The most characteristic disturbance is total body potassium loss.

ketoacidosis (DKA), their presence signifies a severe form of DKA.

Causes 1) Patients with type 1 diabetes

Among individuals with type 1 diabetes, diabetic ketoacidosis is much more common in young children & adolescents than it is in adults.
Clinical

Insidious increased thirst (i.e. polydipsia) & urination (i.e. polyuria) are the most common early symptoms of diabetic ketoacidosis (DKA). Nausea & vomiting usually occur & may be associated with diffuse abdominal pain. Generalized weakness & fatigability may occur. Altered consciousness in the form of mild disorientation or confusion is a possible symptom. Symptoms of possible associated intercurrent infection may include fever, dysuria, coughing, malaise & arthralgia, among others. Signs of dehydration - Weak & rapid pulse, dry tongue & skin, hypotension & increased capillary refill time Patient odor - Characteristic acetone odor to breath Signs of acidosis - Shallow rapid breathing or air hunger (Kussmaul or sighing respiration), abdominal tenderness & disturbance of consciousness Although these signs are not usual in all cases of diabetic
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2)

Diabetic ketoacidosis (DKA) present at diagnosis of type 1 diabetes due to acute insulin deficiency (occurs in 25% of patients) Poor compliance with insulin through the omission of insulin injections either due to lack of patient or guardian education or as a result of psychological stress, particularly in adolescents Bacterial infection & intercurrent illness (e.g. UTI, vomiting) Medical, surgical, or emotional stress Brittle diabetes Idiopathic (no identifiable cause) Insulin infusion catheter blockage Mechanical failure of insulin infusion pump
Patients with type 2 diabetes

Intercurrent illness (e.g. myocardial infarction, pneumonia, prostatitis, UTI) Medication (e.g. corticosteroids, pentamidine, clozapine) Sepsis, Bacterial Toxicity, Salicylate

Differential Diagnoses

Physical

Alcoholic Ketoacidosis Hyperosmolar Coma Lactic Acidosis Metabolic Acidosis Pancreatitis, Acute

Other problems to be considered

Bacteremia & sepsis Dehydration due to gastroenteritis

Laboratory Studies Urine - This test is highly positive for glucose & ketones by

dipstick testing. Urine culture helps to identify any possible infecting organisms.

Blood & plasma

The blood glucose level usually is higher than 250 mg/dL. Serum ketones are present. Arterial blood gases (ABG) frequently show typical manifestations of metabolic acidosis, low bicarbonate & low pH (< 7.2). BUN frequently is increased. Blood culture findings may help to identify any possible infecting organisms. Electrocardiogram (ECG) This test may reveal signs of acute myocardial infarction that could be painless in patients with diabetes, particularly in those with autonomic neuropathy. T - wave changes may produce the first warning sign of disturbed serum potassium levels. Low T wave & apparent U wave always signify hypokalemia, while peaked T wave is observed in hyperkalemia. ECG should be performed every 6 hours during the first day, unless the patient is monitored

Administer 1 liter every 4 hours, depending on the degree of dehydration & central venous pressure (CVP) readings. When the patient becomes euvolemic, the physician may switch to half the isotonic sodium chloride solution, particularly if hypernatremia exists. When blood sugar decreases to less than 180 mg/dL, isotonic sodium chloride solution is replaced with 5 - 10% dextrose with half isotonic sodium chloride solution. When insulin treatment is started, several points must be considered. A low - dose insulin regimen has the advantage of not inducing severe hypoglycemia or hypokalemia, as may be observed with a high - dose insulin regimen. Only short - acting insulin is used for correction of hyperglycemia. Subcutaneous absorption of insulin is reduced in DKA because of dehydration; therefore, using IV or IM routes is traditionally preferable. Subcutaneous use of the fast - acting insulin analog (lispro) has been tried in pediatric DKA (0.15 U/kg q2h). The initial insulin dose is a continuous IV insulin infusion using an infusion pump, if available, at a rate of 0.1 U/kg/h. A mix of 24 units of regular insulin in 60 mL of isotonic sodium chloride solution usually is infused at a rate of 15 mL/h (6 U/h) until the blood sugar drops to less than 180 mg/dL, then the rate of infusion decreases to 5 - 7.5 mL/h (2 - 3 U/h) until the ketoacidotic state abates. Larger volumes of an insulin & isotonic sodium chloride solution mixture can be used, providing that the infusion dose of insulin is similar. Larger volumes may be easier in the absence of an intravenous infusion pump (e.g.60 U of insulin in 500 mL of isotonic sodium chloride solution at a rate of 50 mL/h). The optimal rate of glucose decline is 100 mg/dL/h. Do not allow the blood glucose level to fall below 200 mg/dL

Insulin

Other Tests

Management

Managing diabetic ketoacidosis (DKA) in an ICU during the first 24 - 48 hours is always advisable. When treating DKA, the points that must be considered & closely monitored include correction of fluid loss with IV fluids; correction of hyperglycemia with insulin; correction of electrolyte disturbances, particularly potassium loss; correction of acid - base balance; & treatment of concurrent infection if present. Fluids - Initial correction of fluid loss is either by isotonic sodium chloride solution or by lactated Ringer solution. Administer 1 liter over the first 30 minutes. Administer 1 liter over the second hour. Administer 1 liter over the following 2 hours.
37

during the first 4 - 5 hours of treatment. Hypoglycemia may develop rapidly with correction of ketoacidosis. A common mistake is to allow blood glucose to drop to hypoglycemic levels. This mistake usually results in a rebound ketosis derived by counter - regulatory hormones. Rebound ketosis requires a longer duration of treatment. The other hazard is that rapid correction of hyperglycemia & hyperosmolarity may shift water rapidly to the hyperosmolar intracellular space & may induce cerebral edema.

Rapid & early correction of acidosis with sodium bicarbonate may worsen hypokalemia & cause paradoxical cellular acidosis. In the presence of infection, administer proper antibiotics guided by the results of culture & sensitivity studies. Starting empiric antibiotics on suspicion of infection until culture results are available may be advisable.

Treatment of concurrent infection

14
Cerebral palsy

Electrolyte correction Potassium

If the potassium level is greater than 6 mEq/L, do not administer potassium supplement. If the potassium level is 4.5 - 6 mEq/L, administer 10 mEq/h of potassium chloride. If the potassium level is 3 - 4.5 mEq/L, administer 20 mEq/h of potassium chloride. Monitor serum potassium levels hourly & the infusion must stop if the potassium level is greater than 5 mEq/L. Monitoring of serum potassium must continue even after potassium infusion is stopped in the case of (expected) recurrence of hypokalemia. In severe hypokalemia, not to starting insulin therapy is advisable unless potassium replacement is underway in order to avoid potentially serious cardiac dysrhythmia that may result from hypokalemia. Sodium bicarbonate only is infused if decompensated acidosis starts to threaten the patients life, especially when associated with either sepsis or lactic acidosis. If sodium bicarbonate is indicated, 100 - 150 mL of 1.4% concentration is infused initially. This may be repeated every half hour if necessary.
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Cerebral palsy is a term which covers a group of non progressive, non - contagious neurological disease which causes physical disability. Cerebral palsy (CP) is a static encephalopathy. It is a disorder of posture & movement often associated with abnormalities of speech, vision & intellect resulting from a defect or lesion of the developing brain. The condition was first described almost 150yr ago by Little, an orthopedic surgeon. The primary causes included birth trauma, asphyxia & prematurity. CP may present from extreme clumsiness (flaccidity) to extensive spasticity.

Pathophysiology

Correction of acid - base balance

The pathophysiology of this condition is uncertain & generally no specific cause is found. However there are certain risk factors which increase the chance of the child developing this condition.
Causes

CP is caused by damage to the developing brain. It usually develops by 2 - 3 years of age. Though most of the causes remain unknown; infections during pregnancy in the mother, severe jaundice in the infant, birth injuries & stress to the fetus in the uterus are some of the known

factors. Babies born prematurely are at a particular risk. Any severe illness damaging the brain in the 1st year of life can result in CP. Prematurity (almost all cerebral palsy babies are premature) Congential infections Birth trauma Hypoxia Chemicals (alcohol, smoking etc.) Breech deliveries Birth defects Low birth weight babies Twin deliveries Abnormally small head (microcephaly). Convulsions shortly after birth.

Risk Factors

Associated problems Mental retardation (IQ < 50) occurs in 30 - 50% but it should be

devlopment. 10% - intrapartum asphyxia. Pre - natal causes - Anoxia, P/v bleeding, cord compression, Maternal toxemia, Maternal infections 4) Natal causes - Anoxia, Asphyxia, Sedatives given to mother, Difficult labor, Breech presentation 5) Post Natal causes - Kernicterus (bilirubin encephalopathy), Trauma, Infections 6) Other - Intrauterine exposure to maternal infection (e.g. chorioamnionitis, inflammation of placental membranes, umbilical cord inflammation (funisitis), foul - smelling amniotic fluid, maternal sepsis, temperature greater than 38C during labor & urinary tract infection) is associated with a significant increase in the risk of CP in normal birth weight infants. 7) High risk in low birth weight infants,. Particularly those weighing less than 1, 000g at birth, Primarily because of intracerebral hemorrhage & periventricular leukomalacia. 2) 3)
Clinical manifestations CP may be classified into

mentioned that cerebral palsy patients generally do not have problems with their intelligence. It associated with spastic quadraplegia Seizures & epilepsy occurs in 21% Blindness occurs in 11% Medical complications are common : GI problems, aspiration pneumonia, dental problems. Ultrasound (in preterm babies) - identifies risk of cerebral palsy CT - to detect structural malformations & vascular abnormalities MRI - white matter lesions, asphyxia Prevalence of 2/1, 000 population 80% factors during antenatal period causing abnormal brain
39

Imaging

Epidemiology & etiology

1)

2) Topographic 4) Functional capacity Physiologic classification = the major motor abnormality, Topographic taxonomy = the involved extremities. CP is also associated with developmental disabilities 1) Mental retardation, 2) Epilepsy, 3) Visual, 4) Hearing, 5) Speech, 6) Cognitive, 7) Behavioral abnormalities. Motor syndrome CNS pathology Major causes Spastic diplegia Periventricular Prematurity, ischemia, leukomalacia (PVL) infection endocrine, metabolic Spastic PVL, multicystic Infection, genetic quadriplegia encephalomalacia Hemiplegia Stroke in utero Infection, genetic

1) Physiologic 3) Etiologic categories

Extra pyramidal Bas basal ganglia, thalamus, putamen

Topographic classification Types of CP 1) Spastic

Kernicterus, infection

It is the most common type in which the muscles are stiff & weak (due to uncontrolled contraction of the muscles). The stiffness may occur in both legs (diplegia), in the leg & arm on the same side (hemiplegia), or in all four limbs (quadriplegia). These children usually show toe walking & typical crossed (scissoring) gait. The main symptom of spastic cerebral palsy is spasticity (muscle overactivity resulting in resistance to stretching). This is further classified into hemiplegic, quadraplegic & diplegic spastic cerebral palsy based on which part of the body it affects. Hemiplegic - arm & leg on same side Diplegic - both legs but arms far less Quadraplegic - whole body
A) Spastic hemiplegia

the ankle, causing an equinovarus deformity of the foot. An affected child often walks on tiptoes because of the increased tone & the affected upper extremity assumes a dystonic posture when the child runs. 6) Ankle clonus & a Babinski sign may be present, the deep tendon reflexes are increased & weakness of the hand & foot dorsiflexors is evident. About one third of patients with spastic hemiplegia have a seizure disorder that usually develops during the first year or two & approximately 25% have cognitive abnormalities including mental retardation. 7) A CT scan or MRI may show an atrophic cerebral hemisphere with a dilated Lateral ventricle, contra lateral to the side of the affected extremities. Intrauterine thromboembolism with focal cerebral infarction may be one cause; CT or MRI at birth in infants with focal seizures often demonstrates the area of infarction. Spastic hemiplegia is more common than spastic diplegia in low birthweight infants.
B) Spastic diplegia

1)

1)

2)

3) 4)

5)

Decreased spontaneous movements on the affected side & show hand preference At a very early age. The arm is often more involved than the leg & difficulty in hand manipulation is Obvious by 1yr of age. Walking is usually delayed until 1824 mo & a circumductive gait is apparent. Examination of the extremities may show growth arrest, particularly in the hand & thumbnail, especially if the contra lateral parietal lobe is abnormal, because this area of the brain influences extremity growth. Spasticity is apparent in the affected extremities, particularly
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2) 3)

4) 5)

Bilateral Spasticity of the legs. The first indication of spastic diplegia is often noted when an affected infant begins to crawl. The child uses the arms in a normal reciprocal fashion but tends to drag the legs behind more as a rudder (commando crawl) rather than using the normal four - limbed crawling movement. If the Spasticity is severe, application of a diaper is difficult owing to excessive adduction of the hips. Examination of the child reveals Spasticity in the legs with brisk reflexes, ankle clonus & a bilateral Babinski sign. When the child is suspended by the axillae, a scissoring posture of the lower extremities is maintained. Walking is significantly delayed; the feet are held in a position of equinovarus; & the child walks on tiptoes. Severe spastic diplegia is characterized by disuse atrophy & impaired growth of the lower extremities & by disproportionate

growth with normal development of the upper torso. The prognosis for normal intellectual development is excellent for these patients & the likelihood of seizures is minimal. The most common neuro pathologic finding is periventricular leukomalacia, particularly in the area where fibers innervating the legs course through the internal capsule. 6)
C) Spastic quadriplegia

4)

prominent. Speech is typically affected owing to involvement of the oropharyngeal muscles. Sentences are slurred & voice modulation is impaired. Generally, upper motor Neuron signs are not present, seizures are uncommon & intellect is preserved in most patients.
Ataxic

3)

1)

2) 3)

4) 5)

6)
2)

The most severe form of CP because of marked motor impairment of all extremities & the high association with mental retardation & seizures. Swallowing difficulties are common owing to supranuclear bulbar palsies & they often lead to aspiration pneumonia. Neurologic examination shows increased tone & spasticity in all extremities, decreased spontaneous movements, brisk reflexes & plantar extensor responses. Flexion contractures of the knees & elbows are often present by late childhood. Associated developmental disabilities, including speech & visual abnormalities are particularly prevalent in this group of children. Children with spastic quadriparesis often have evidence of athetosis & may be classified as having mixed CP.
Athetoid CP / extra pyramidal / Dyskinetic CP

This generally affects balance, causes hand tremors which affects reading & writing & can cause speech problems. Hypotonia (rather than spasticity) may also be present.
4) Hypotonic CP

These children usually present with low muscle tone & increased floppiness. These children eventually develop spasticity or athetosis.
Diagnosis

1) 2) 3)

4)

Patients with this type of CP have bizarre twisting motions or unusual posturing. This is characterised by involuntary movements & a progression from hypotonia to hypertonia. Due to these differences in muscle tone & the involuntary movements, staying in steady positions such as standing upright or sitting still can be difficult. 1) Rare, especially since the advent of aggressive management of hyperbilirubinemia & the prevention of kernicterus. 2) Affected infants are characteristically hypotonic & have poor head control & marked head lag. 3) Feeding may be difficult & tongue thrust & drooling may be

5) 6)

7) 8)

History Physical examination Exclude progressive disorder of the CNS, including degenerative diseases, spinal Cord tumor, or muscular dystrophy. Parents may first notice that their child is not developing motor milestones normally i.e. the baby may have delayed rolling over or the baby may be late to sit, crawl or walk. The child may also show an unusual posture or favor one side of their body. Electroencephalogram (EEG) & CT scan - to determine the location & extent of structural lesions or associated congenital malformations. Tests of hearing & visual function. Multidisciplinary approach is most helpful in the assessment & treatment of such children.

Management

CP is a lifelong condition & cannot be cured. However, treatment may improve the quality of life by increasing independent
41

mobility. The treatment not only depends on the patients symptoms but also his age. Patients with severe muscle contractures may require surgery to lengthen the muscle or some spinal surgery to reduce spasticity in the legs Medication may also be given to decrease the muscle spasticity. Now, botulinum toxin injections are available which when used with physical therapy, help in lengthening a muscle. Baclofen pumps are also available to control spastically for a longer period of time. Physical therapy, which consists of special exercises, may increase the movement & strength of the muscles. Occupational therapy may be required to develop skills to carry out day to day activities at home. A variety of mechanical aids like braces, speech synthesizer may be required. For children with speech problems, speech therapy is required. In addition, medications may be required to control the seizures. Some children with learning disabilities & mental retardation may require special learning programs.
Medical treatment Muscle relaxants are used to treat the spasticity, including

If a patient has marked spasticity of the lower extremities or evidence of hip dislocation, consideration should be given to performing surgical soft tissue procedures that reduce muscle spasm around the hip girdle, including an adductor Tenotomy or Psoas transfer & release. A Rhizotomy procedure in which the roots of the spinal nerves are divided has produced considerable improvement in selected patients with severe spastic diplegia. A tight heel cord in a child with spastic hemiplegia may be treated surgically by tenotomy of the Achilles tendon.

Other interventions Mobility aids are very important - mobility is one of the biggest

issues in cerebral palsy & this is where the occupational therapist is at the most useful. Finally, care for the carriers is also important. In any chronic disabling condition, the people looking after the patient are at a higher risk of developing psychological but also physical health problem.
Prognosis

Dantrolene sodium, the Benzodiazepines (Diazepam) & Baclofen. Intrathecal Baclofen used in selected children with severe spasticity. Patients with incapacitating athetosis occasionally respond to Levodopa & children with dystonia may benefit from Carbamazepine or Trihexyphenidyl. There are also a variety of injections which can be given to relieve muscle spasticity in specific muscle groups (such as botulinum toxin or phenol).
Surgery

This is incredibly variable. Mild forms of the disease will mean that the patient probably has a normal life expectancy but at its most severe, the chances of reaching the age of 20 yrs drops to 40%. Severity would include severe quadriplegia, epilepsy, mental retardation & medical complications (gasto - oesophageal reflux or pneumonias).
Measures to be taken

There are a variety of surgical procedures.

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1. Handling, 2. Exercise 3. Equipments 4. Soft tissue surgery 5. Spinal cord surgery 6. Motorized wheel 7. Communication, 8. behavior, 9. mental Retardation, 10. eye, 11. UTI, 12. drugs 1) Parents should be taught how to handle their child in daily activities such as feeding, carrying, dressing, bathing & playing in ways that limit the effects of abnormal muscle tone. 2) They also need to be instructed in the supervision of a series of exercises designed to prevent the development of contractures, especially a tight Achilles tendon. There is no proof that physical or occupational therapy prevents development of CP

3) 6)

7)

8) 9) 10) 11)

in infants at risk or that it corrects the neurologic deficit, but ample evidence shows that therapy optimizes the development of an abnormal child. Children with spastic diplegia are treated with equipment, such as walkers, poles & standing frames. Quadriplegia is managed with motorized wheelchairs, special feeding devices, modified typewriter & customized seating arrangements. Communication skills may be enhanced by the use of bliss symbols, talking typewriters & specially adapted computers including artificial intelligence computers to augment motor & language function. Behavior problems interfere with the development of a child with cp; assistance of a psychologist or psychiatrist. Learning & Attention deficit disorders & Mental retardation managed by a psychologist & educator. Strabismus, Nystagmus & optic atrophy consult with ophthalmologist - in the initial assessment. Lower urinary tract dysfunction should receive prompt assessment & treatment.

initial hemorrhage, vitamin K deficiency bleeding is usually classified by 3 distinct time periods after birth, as follows :
Early - onset vitamin K deficiency bleeding in the newborn

Prevention

The pregnant mother should get regular antenatal care. Blood tests of mothers should be checked to detect Rh factor. Parents should seek treatment for a baby who is jaundiced at birth or has prolonged jaundice within a few days after birth.

Early - onset vitamin K deficiency bleeding usually occurs during first 24 hours after birth. It is seen in infants born to mothers taking anticonvulsant or anti - tuberculosis medication. Serious hemorrhagic complications can occur in this type of hemorrhage. The mechanisms by which anticonvulsant & anti - tuberculosis medications cause vitamin K deficiency bleeding in neonates is not clearly understood, but limited studies suggest that vitamin K deficiency bleeding is a result of vitamin K deficiency & can be prevented by administration of vitamin K to the mother during the last 2 - 4 weeks of pregnancy. Vitamin K supplementation given after the birth for early onset vitamin K deficiency bleeding may be too late to prevent this disease, especially if vitamin K supplementation was not provided during pregnancy. Numerous maternal medications and/or exposure to toxins during pregnancy are associated with vitamin K deficiency bleeding in neonates (e.g. anticonvulsants [e.g. phenytoin, barbiturates, carbamazepine], anti - tubercular drugs [e.g. rifampin, isoniazid], vitamin K antagonists [e.g. warfarin, phenprocoumon]). Classic vitamin K deficiency bleeding usually occurs after 24 hours & as late as the first week of life. Classic vitamin K deficiency bleeding is observed in infants who have not received prophylactic vitamin K at birth. The incidence of classic vitamin K deficiency bleeding ranges from 0.25 - 1.7 cases per 100 births. Usually the disease occurs from the second day of life to the end of the first week; however, it can occur during first month

15
In the past, the term hemorrhagic disease of the newborn was used to describe bleeding disorders in neonates associated with a traumatic birth or hemophilia. The proper diagnostic term that has been adopted is currently vitamin K deficiency bleeding because vitamin K deficiency is not the sole cause of hemorrhagic disorders in preterm & term infants. Although some controversy surrounds postnatal timing of the
43

Classic vitamin K deficiency bleeding in the newborn

& sometimes overlaps with late - onset vitamin K deficiency bleeding. Infants who have classic vitamin K deficiency bleeding are often ill, have delayed feeding, or both. Bleeding commonly occurs in the umbilicus, GI tract (i.e. melena), skin, nose, surgical sites (i.e. circumcision), and, uncommonly, in the brain. This usually occurs between age 2 - 12 weeks; however, late onset vitamin K deficiency bleeding can be seen as long as 6 months after birth. This disease is most common in breastfed infants who did not receive vitamin K prophylaxis at birth. Vitamin K content is low in mature human milk & ranges from 1 - 4 mcg/L. Industrial contaminants in breast milk have been implicated in promoting vitamin K deficiency bleeding. More than half of these infants present with acute intracranial hemorrhages.

Pathophysiology

Late - onset vitamin K deficiency bleeding in the newborn

Currently, the following 3 forms of vitamin K are known

K1 : Phylloquinone is predominantly found in green leafy vegetables, vegetable oils & dairy products. Vitamin K given to neonates as a prophylactic agent is an aqueous, colloidal solution of vitamin K1. K2 : Menaquinone is synthesized by gut flora. K3 : Menadione is a synthetic, water soluble form that is no longer used medically because of its ability to produce hemolytic anemia. Coagulation factors II, VII, IX & X & other Gla - proteins (e.g. protein C, protein S, protein Z) also depend on the presence of vitamin K for their activity. The role of Gla proteins is not completely understood. Vitamin K deficiency gives rise to abnormal prothrombin levels; thus, prothrombin does not effectively participate in blood clot formation.
44

Newborn infants are at risk of developing vitamin K deficiency & this coagulation abnormality leads to serious bleeding. Transplacental transfer of vitamin K is very limited during pregnancy & the storage of vitamin K in neonatal liver is also limited. This makes the newborn infant vulnerable to hemorrhagic disorders unless exogenous vitamin K is given for prevention of bleeding immediately after birth. Once the infantile gut is colonized with bacterial flora, the microbial production of vitamin K results in a lower risk of infantile vitamin K deficiency bleeding. A gut - related microbial source of vitamin K is particularly important if dietary phylloquinone is restricted. The most common sites of hemorrhage or bleeding are the umbilicus, mucus membrane, GI tract, circumcision & venipuncture sites. Hematomas frequently occur at the sites of trauma (i.e. large cephalohematomas, scalp bruising related to instrumentation used at delivery, and, rarely, intracranial hemorrhage). Placental transfer of vitamin K is very limited & phylloquinone (vitamin K1) levels in umbilical cord blood is very low. The newborn infants intestinal tract is relatively sterile & takes some time to colonize with bacteria, which may have a role in synthesizing vitamin K2 (menaquinones). Because Bacteroides species are among the most common bacteria that inhabit the human intestinal tract & because strains such as Bacteroides fragilis synthesize vitamin K, Bacteroides species are more significant in producing human vitamin K in the intestine than Escherichia coli. Breast milk is a poor source of vitamin K (breast milk levels are 1 - 4 g/L). The recommended dietary intake of vitamin K is 1 g/kg/d. Exclusively breastfed infants have intestinal colonization with lactobacilli that do not synthesize vitamin K; thus, reduced production of menaquinones increases the neonatal risk of developing a hemorrhagic disorder if not supplemented with vitamin K. Formula fed infants have higher fecal concentrations of vitamin K1 because of

dietary intake & significant quantities of fecal menaquinones, reflecting the guts microflora. Preterm infants who are receiving total parenteral nutrition (TPN) are not at risk because they are receiving vitamin K via the multivitamin additive to the TPN. Special consideration is needed for very low birth weight infants whose intestinal tract bacterial flora is altered because of multiple courses of broad - spectrum antimicrobials. Once preterm infants are weaned off of TPN, they may develop vitamin K deficiency if they are exclusively fed breast milk.
Mortality / Morbidity

Signs of intracranial hemorrhage include apnea with or without seizures & a shocklike syndrome. Internal hemorrhage of organs other than the brain may be difficult to detect; however, if they are suspected, careful physical monitoring & serial imaging after birth are indicated. Soft tissue hemorrhage is easier to recognize, but sequential measurements of the bleeding into soft tissues or muscle are mandatory. Vitamin K deficiency in the newborn can be present for various reasons Maternal medications that interfere with vitamin K stores or function (e.g. carbamazepine, phenytoin, barbiturates, some cephalosporins, rifampin, isoniazid, warfarin or warfarin like drugs) can result in vitamin K deficiency bleeding in the infant. In addition to breastfeeding, clinical states that are risk factors for late - onset vitamin K deficiency bleeding include : Diarrhea Hepatitis Cystic fibrosis Celiac disease Alpha1 - antitrypin deficiency Short bowel syndrome Intestinal bacterial overgrowth Chronic exposure to broad spectrum antimicrobials Consumption Coagulopathy Von Willebrand Disease

Causes

Intracranial hemorrhage is uncommon in classic vitamin K deficiency bleeding but can be observed in more than 50% of infants with late - onset vitamin K deficiency bleeding. Intracranial hemorrhage is responsible for nearly all mortality & long - term sequelae due to vitamin K deficiency bleeding.
Age

o o o o o o o o

Vitamin K deficiency bleeding is mostly a disease of the newborn but such hemorrhage can occur beyond the neonatal period, especially if conditions such as short gut syndrome, intestinal bacterial overgrowth & certain genetic conditions are present.
History

The maternal history is very important when assessing vitamin K deficiency bleeding (VKDB), especially the medications used during pregnancy, the presence of medical conditions such as short gut syndrome & unusual dietary intakes. Better surveillance during pregnancy & careful medical evaluation of neonate after delivery are essential. Most newborn infants are healthy upon examination, even if early onset bleeding is present; however, intracranial hemorrhage can occur during the birthing process & can lead to severe complications.
45

Differential diagnosis Other Problems to Be Considered

Physical

Maternal isoimmune thrombocytopenia Alloimmune thrombocytopenia Hepatobiliary disease Uncommon coagulopathies

Laboratory Studies

A prothrombin time (PT), activated partial thromboplastin time

o o

(aPTT), fibrinogen levels & a platelet count should be included in the initial workup for vitamin K deficiency bleeding (VKDB) in a newborn. A thrombin clotting time (TCT) is optional. A prolonged PT is usually the first laboratory test result to be abnormal in vitamin K deficiency bleeding; however, no laboratory test result can confirm the diagnosis of vitamin K deficiency bleeding. A direct blood measurement of vitamin K is not useful because levels normally are low in newborns. Levels of protein induced by vitamin K antagonism (PIVKA II) are increased in vitamin K deficiency bleeding, but this test is generally not available outside of research laboratories. Infants with vitamin K deficiency bleeding typically have a prolonged PT with platelet counts & fibrinogen levels within the normal range for newborns. Thrombocytopenia or a prolonged aPTT should prompt workup for other causes of bleeding during the neonatal period. The diagnosis of vitamin K deficiency bleeding is confirmed if administration of vitamin K halts the bleeding & reduces the PT value.

coagulopathy. Intravenous (IV) administration of vitamin K has been associated with anaphylactoid like reactions. Fresh frozen plasma may be considered for moderate - to severe bleeding. Life - threatening bleeding may also be treated with prothrombin complex concentrates (PCC). Because the bleeding in classic vitamin K deficiency bleeding usually is not life threatening, a single dose of parenteral vitamin K is sufficient to stop the bleeding & return prothrombin time (PT) values to the reference range. Oral vitamin K has been studied as an alternative & can improve clotting studies & vitamin K levels, but it has not been studied in large randomized controlled trials to determine if this strategy effectively prevents early & late vitamin K deficiency bleeding. Breastfed infants should receive vitamin K supplementation; if mothers refuse prophylaxis, they should be counseled. Because breast milk is not a good source of vitamin K, infants of mothers who refuse prophylaxis & who exclusively breastfeed should have receive oral supplementation of vitamin K. A recent recommendation for oral vitamin K supplementation in term infants suggest weekly administration of 1 mg until age 12 weeks or 2 mg at birth repeated at age 1 week & age 4 weeks, but this recommendation emphasizes a lack of information related to dosing of oral vitamin K in preterm infants. An additional oral dose of 2 mg at age 8 weeks has also been suggested. The best sources are green leafy vegetables, legumes, soybean & olive oils.

Diet

Medical Care

Prevention of vitamin K deficiency bleeding (VKDB) with intramuscular vitamin K is of primary importance in the medical care of neonates. A single dose of intramuscular vitamin K after birth effectively prevents classic vitamin K deficiency bleeding. Conversely, oral vitamin K prophylaxis improves coagulation test results at 1 - 7 days, but vitamin K administered by this route has not been tested in randomized trials for its efficacy in preventing either classic or late vitamin K deficiency bleeding. Immediately administer vitamin K subcutaneously (hold pressure on the site) for any infant in whom vitamin K deficiency bleeding is suspected or who has serious, unexplained neonatal bleeding. IM administration can result in a hematoma because of the
46

Activity

During acute bleeding, the infant with vitamin K deficiency bleeding should be handled with caution until the coagulation profile

returns to normal after vitamin K supplementation. Vitamin K is the mainstay for prevention of & treatment of vitamin K deficiency bleeding (VKDB). Other coagulation factors are rarely needed. Severe bleeding may warrant the use of fresh frozen plasma. No other drugs or treatments are acceptable substitutes for prompt vitamin K dosing. Subcutaneous administration of vitamin K is preferred over the intramuscular (IM) route in symptomatic infants.
Vitamins

prolonged bleeding in a patient. Hemophilia is one of the oldest described genetic diseases
A person with hemophilia does not bleed faster, only bleeds longer

Vitamin K is required to correct the deficiency that defines vitamin K deficiency bleeding. Prophylaxis with IM vitamin K at birth is an effective means of preventing vitamin K deficiency bleeding in the newborn.
Phytonadione K1

Fat - soluble vitamin that promotes the hepatic synthesis of the following clotting factors : prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX) & Stuart factor (factor X).
Pediatric

Prophylaxis at birth : > 32 wk gestation : 0.5 - 1 mg IM Preterm infants < 32 wk gestation : Birth weight > 1000 grams : 0.5 mg I M Birth weight < 1000 grams : 0.3 mg/kg SC/IM Healthy, term & exclusively breast fed infants : 2 mg PO with the first feeding & then at ages 1, 4 & 8

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Hemophilia

There are two types of hemophilia - Hemophilia A & Hemophilia B. The 2 disorders are considered together because of their similar clinical pictures & similar patterns of inheritance. Hemophilia A results from deficiency or abnormality of clotting factor in the blood called as factor VIII. Making up approximately 80% of hemophilia cases, hemophilia A (HA), considered the classic form of the disease, results from a congenital deficiency of factor VIII (FVIII). Hemophilia B results from deficiency or abnormality of another clotting factor called as factor IX. Hemophilia B (HB), also called Christmas disease, is a consequence of a congenital deficiency of factor IX (FIX). In 1952, Christmas disease was described & named after the surname of the first patient who was examined in detail. This disease was distinct from hemophilia because mixing plasma from a patient with true hemophilia & with plasma from a patient with Christmas disease corrected the clotting time; thus, hemophilia A & B were differentiated. These deficiencies result in an insufficient generation of thrombin by FIXa & FVIIIa complex through the intrinsic pathway of the coagulation cascade. Females are usually carriers (i.e. they have the abnormal gene that causes hemophilia but do not have clinical manifestations). The male children usually manifest/suffer the disease. Sometimes hemophilia occurs due to a fresh mutation in the gene sequence in the child.

Hemophilia is an inherited disorder in which there is inability to form an effective clot caused by deficiencies of clotting factor VIII (FVIII) & factor IX (FIX), respectively & hence causes
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The following permutations - combinations can occur while inheriting hemophilia 1) Normal Mother + Father with hemophilia

During each pregnancy, the female offspring has 100% chance

of being a carrier & the male offspring is always normal. Hence, sons of hemophiliac fathers & normal mothers are normal.
2) Carrier Mother + Normal Father

spontaneous hemarthrosis & soft tissue bleeding in the absence of precipitating trauma.
Pathophysiology

During each pregnancy, there is 25% chance of a normal female, 25% chance of a carrier female, 25% chance of a normal male & 25% chance of an affected male.
3) Carrier Mother + Father with hemophilia

The role of the coagulation system is to produce a stable fibrin clot at sites of injury. The clotting mechanism has 2 pathways : intrinsic & extrinsic.
Coagulation system

Each pregnancy has 25% chance of a female carrier, 25% chance a female with hemophilia, 25% chance of a normal male & 25% chance of an affected male.
4) Mother with hemophilia + Father with hemophilia

During each pregnancy there is 50% chance of an affected female & a 50% chance of an affected male (actual occurrence is rare).
5) Mother with Hemophilia + Normal Father

During each pregnancy there is 50% chance of a carrier female & a 50% chance of an affected male though the actual occurrence is rare.
Classification

Hemophilia are divided into severe, moderate & mild diseases depending on the level of functional factor VIII or factor IX. (Normal levels are between 50% & 150%). Mild hemophiliacs (factor levels> 5% & < 50%) bleed only after injury, invasive procedure or surgery. Carriers of hemophilia are also sometimes found to have factor levels in the Mild range. Patients with mild hemophilia have more than 5% factor VIII (FVIII) activity & bleed only after significant trauma or surgery. Moderate hemophiliacs (factor levels - 2 to 5%) experience more bleeds, about once a month, usually after trauma, surgery or extreme exertion. They usually bleed in the muscles & joints. Severe hemophiliacs (factor level< 1%) bleed spontaneously usually in joints, muscles & soft tissues. It is characterized by
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The intrinsic system is initiated when factor XII is activated by contact with damaged endothelium. The activation of factor XII can also initiate the extrinsic pathway, fibrinolysis, kinin generation & complement activation. In conjunction with high - molecular - weight kininogen (HMWK), factor XIIa converts prekallikrein (PK) to kallikrein & activates factor XI. Activated factor XI, in turn, activates factor IX in a calcium - dependent reaction. Then, factor X is activated on the cell surface; activation of factor X involves a complex (tenase complex) of factor IXa, thrombin - activated FVIII, calcium ions & phospholipid. In the extrinsic system, the conversion of factor X to factor Xa involves tissue factor (TF), or thromboplastin; factor VII; & calcium ions. TF is released from the damaged cells. Factor IXa & factor XII fragments can also activate factor VII. In the common pathway, factor Xa (generated through the intrinsic or extrinsic pathways) forms a prothrombinase complex with phospholipids, calcium ions & thrombin - activated factor Va. The complex cleaves prothrombin into thrombin & prothrombin fragments 1 & 2. Thrombin converts fibrinogen into fibrin & activates FVIII, factor V & factor XIII. Fibrinopeptides A & B, the results of the cleavage of peptides A & B by thrombin, cause fibrin monomers to form & then polymerize into a meshwork of fibrin; the resultant clot is stabilized by factor XIIIa & the cross - linking of adjacent fibrin strands. FV III & FI X circulate in an inactive form. When activated, these 2 factors cooperate to cleave & activate factor X, a key enzyme that controls the conversion of fibrinogen to fibrin. Therefore, the

lack of either of these factors may significantly alter clot formation and, as a consequence, result in clinical bleeding. The genes for both F VIII (i.e. hemophilia A) & F IX (i.e. hemophilia B) are located on the long arm of chromosome X.
Sex

Ask about the patients family history & bleeding symptoms.

Both forms of hemophilia are sex - linked coagulopathies because they are inherited as X - linked recessive disorders; therefore, the disease primarily affects male individuals. Female individuals who carry the affected genes usually do not have bleeding manifestations. Female patients may have clinical bleeding due to hemophilia if 1 of 3 conditions is present : 1) Extreme lionization (Lyonized females (i.e. those with unequal inactivation of FVIII or FIX alleles & with hemizygosity of all or part of the X chromosome) may be symptomatic) 2) Homozygosity for the hemophilia gene (e.g. father with hemophilia & mother who is a carrier), or 3) Turner syndrome (XO) associated with the affected hemophilia gene (on average, only the X chromosome). Life - threatening hemorrhage is also a significant problem. Intracranial hemorrhage is a life - threatening hemorrhage with a lifetime risk. Other life - threatening hemorrhages include soft - tissue hemorrhages that obstruct airways or damage the internal organs. Intracranial hemorrhage is the second most common cause of death & the most common cause of death related to hemorrhage.
Age

Male patients with severe hemophilia present at circumcision. Easy bruising may occur at the start of ambulation or primary dentition. The patient may have a history of hemarthroses & prolonged bleeding with surgical procedures, trauma, dental extraction & he or she may have spontaneous bleeding in soft tissues.

The principal sites of bleeding in patients with hemophilia are as follows :

For joints, weight - bearing joints & other joints are affected. Regarding muscles, those most commonly affected are the flexor groups of the arms & gastrocnemius of the legs. Iliopsoas bleeding is dangerous because of the large volumes of blood loss & because of compression of the femoral nerve. In the genitourinary tract, gross hematuria may occur. In the GI tract, bleeding may complicate common GI disorders. Bleeding in the CNS is the leading cause of hemorrhagic death among patients with hemophilia.
Factor Activity % Cause of Hemorrhage

Severity, Factor Activity & Hemorrhage Type Classification

Significant deficiency in FVIII or FIX may be evident in the neonatal period & continue through the life of the affected individual. The absence of hemorrhagic manifestations at birth does not exclude hemophilia.
Clinical
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Mild > 5 - 40 Major trauma / surgery Moderate 1-5 Mild - to - moderate trauma Severe <1 Spontaneous, hemarthrosis Direct the examination to identify signs related to spontaneous or, with minimal challenge, bleeding in the joints, muscles & other soft tissues. Observe the patients stature. Examine the weight - bearing joints, especially the knees & ankles, and, in general, the large joints for deformities or ankylosis. Look for jaundice, other signs of liver failure (e.g. cirrhosis from viral infection) & signs of opportunistic infections in patients who are HIV seroconverted.

Causes

Both of these disorders are inherited in an X - linked recessive pattern. The genes for FVIII & factor IX (FIX) are located on the long arm of the X chromosome in bands q28 & q27, respectively. Numerous mutations are also described in the gene structure. Hemophilia A & hemophilia B are a consequence of a congenital deficit of FVIII & FIX, respectively. The defect results in the insufficient generation of thrombin by the FIXa & FVIIIa complex by means of the intrinsic pathway of the coagulation cascade.
Differential diagnosis

severity of hemophilia. Usually, the activated partial thromboplastin time (aPTT) is prolonged; however, normal aPTT does not exclude mild or even moderate hemophilia because of the relative insensitivity of the test. Severe hemophilia is easily identified with a significantly prolonged aPTT. Bleeding time, prothrombin time & platelet counts are normal. Differentiation of hemophilia A from von Willebrand disease is possible by observing normal or elevated levels of von Willebrand factor antigen & ristocetin cofactor activity.
Bleeding time is prolonged in patients with von Willebrand disease but normal in patients with hemophilia.

Ehlers - Danlos Syndrome Factor V Factor VII Factor XI Deficiency Glanzmann Thrombasthenia
Other problems to be considered

Platelet Disorders von Willebrand Disease

Laboratory confirmation of a FVIII or FIX inhibitor is clinically important when bleeding is not controlled after adequate amounts of factor concentrate are infused during a bleeding episode. Patients with severe hemophilia can bleed from any anatomic site after negligible or minor trauma, or they may even bleed spontaneously. Any physical activity may trigger bleeding in soft tissues. Prophylactic factor replacement early in life may help prevent bleeding, as well as chronic arthritic & muscular damage & deformity.

Activity

Other congenital bleeding disorders must be excluded. These may include the following : Von Willebrand disease (autosomal dominant transmission) Platelet disorders (e.g. Glanzmann thrombasthenia) Deficiency of other coagulation factors, i.e. FV, FVII, FX, FXI, or fibrinogen Acquired hemophilia Differentiating between severe hemophilia A & hemophilia B is almost clinically impossible, but specific laboratory factor assays can help with the distinction. Conditions that can increase FVIII levels (e.g. age, ABO blood type, stress, exercise) can obscure the diagnosis of hemophilia A. The diagnosis of hemophilia B may be delayed by physiologically low levels of all vitamin Kdependent coagulation factors.
Laboratory Studies

Medical care

The plasma concentration of FVIII or FIX determines the

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Before a patient with hemophilia is treated, the following information should be obtained : 1) The type & severity of factor deficiency, 2) The nature of the hemorrhage or the planned procedure, 3) The patients previous treatments with blood products, 4) The presence & possible titers of inhibitors, and 5) The patients previous history of desmopressin acetate (DDAVP) use (e.g. in mild hemophilia A only) with the degree of response & clinical outcome.

Various FVIII & FIX concentrates are now available to treat hemophilia A & hemophilia B. Recombinant FVIII & FIX are now commercially available. They have lowered the risk of viral contamination. Pain medications are used for acute bleeding or chronic arthritis. Safe analgesics include acetaminophen, oxycodone, propoxyphene & pentazocine. Avoid all aspirin products. Plasmapheresis, IVIG, or immunosuppressive therapy with cyclophosphamide & prednisone, have showed some success in achieving long - term control. Current treatment of patients with hemophilia requires a comprehensive multidisciplinary approach, with specialists in hematology, orthopedics, dentistry & surgery; nurses; physiotherapists; social workers; & related allied health professionals. Comprehensive care clinics are supported by evidence of better access to care, less morbidity & better overall outcome. Hospitalization is reserved for severe or life - threatening bleeds, such as large soft tissue bleeds; retroperitoneal hemorrhage; & hemorrhage related to head injury, surgery, or dental work. The treatment of hemophilia may involve management of hemostasis, management of bleeding episodes, use of factor replacement products & medications, treatment of patients with factor inhibitors & treatment & rehabilitation of patients with hemophilia synovitis.
Management of hemostasis

Many recombinant FVIII concentrates are now available. The advantage of such products is the elimination of viral contamination. Third - generation products without any exposure to animal proteins are now available to further decrease this risk. The effectiveness of these products appears comparable to that of plasma - derived concentrates. Concerns regarding higher incidences of the presence of inhibitor appear to be unwarranted.

17 18
Sepsis

Hemostasis is achieved with replacement therapy aimed at correcting the coagulation factor deficiency.
Factor replacement products & medications

FVIII products Various products are available for replacement therapy. Fresh frozen plasma & cryoprecipitate are no longer used in hemophilia A & B because of the lack of safe viral elimination & concerns regarding volume overload.
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Sepsis is a common, deadly & often underappreciated disease process in emergency departments. The basis of sepsis is the presence of infection associated with a systemic inflammatory response that results in physiologic alterations that occur at the capillary endothelial level. Clinicians often use the terms sepsis, severe sepsis & septic shock without a commonly understood definition. Sepsis is the presence of infection in association with meeting SIRS criteria. The clinical significance of meeting SIRS criteria in the absence of organ dysfunction or shock is still unclear. Severe sepsis is defined as evidence of end - organ dysfunction such as altered mental status, episode of hypotension, elevated creatinine, or evidence of disseminated intravascular coagulopathy. Septic shock is defined as persistent hypotension despite adequate fluid resuscitation or tissue hypoperfusion manifested by a lactate greater than 4 mg/dL. Bacteremia is defined as the presence of viable bacteria within the liquid component of blood. Bacteremia may be primary (without an identifiable focus of infection) or, more often,

secondary (with an intravascular or extravascular focus of infection). While sepsis is commonly associated with bacterial infection, bacteremia is not a necessary ingredient in the activation of the inflammatory response that results in severe sepsis. The systemic inflammatory response syndrome (SIRS) as a group of vital signs & a laboratory value that if abnormal may indicate that sepsis physiology is occurring at the microvascular & cellular level. Meeting SIRS criteria is defined by the having at least 2 of the following 4 abnormalities : Temperature higher than 38C or lower than 36C Heart rate greater than 90 beats per minute Respiratory rate greater than 20 breaths per minute WBC count higher than 12, 000/mm3 or lower than 4, 000/ mm3 or with more than 10% immature forms (bands) Of course, a patient can have either severe sepsis or septic shock without meeting SIRS criteria & conversely, SIRS criteria may be present in the setting of many other illnesses. Neonatal sepsis may be categorized as early or late onset. Onset is most rapid in premature neonates. Early onset sepsis syndrome is associated with acquisition of microorganisms from the mother. Transplacental infection or an ascending infection from the cervix may be caused by organisms that colonize in the mothers genitourinary tract, with acquisition of the microbe by passage through a colonized birth canal at delivery. The microorganisms most commonly associated with early onset infection include group B Streptococcus (GBS), Escherichia coli, coagulase - negative Staphylococcus, Haemophilus influenzae & Listeria monocytogenes. Late - onset sepsis syndrome occurs at 4 - 90 days of life & is acquired from the care giving environment. Organisms that have been implicated in causing late - onset
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sepsis syndrome include coagulase - negative staphylococci, Staphylococcus aureus, E coli, Klebsiella, Pseudomonas, Enterobacter, Candida, GBS, Serratia, Acinetobacter & anaerobes. The infants skin, respiratory tract, conjunctivae, GI tract & umbilicus may become colonized from the environment, leading to the possibility of late - onset sepsis from invasive microorganisms. Vectors for such colonization may include vascular or urinary catheters, other indwelling lines, or contact from caregivers with bacterial colonization. Pneumonia is more common in early onset sepsis, whereas meningitis & bacteremia are more common in late - onset sepsis. Premature & ill infants have an increased susceptibility to sepsis & subtle nonspecific initial presentations; therefore, they require much vigilance so that sepsis can be effectively identified & treated.
Pathophysiology Cellular immunity

The neonatal neutrophil or polymorphonuclear (PMN) cell, which is vital for effective killing of bacteria, is deficient in chemotaxis & killing capacity. Also, neonatal PMNs are less deformable; therefore, they are less able to move through the extracellular matrix of tissues to reach the site of inflammation & infection. The limited ability of neonatal PMNs for phagocytosis & killing of bacteria is further impaired when the infant is clinically ill. Lastly, neutrophil reserves are easily depleted because of the diminished response of the bone marrow, especially in the premature infant. Although T cells are found in early gestation in fetal circulation & increase in number from birth to about age 6 months, these cells represent an immature population. A delay occurs in the formation of antigen specific memory function following primary infection &

the cytotoxic function of neonatal T cells is 50 - 100% as effective as adult T cells. At birth, neonates are deficient in memory T cells. As the neonate is exposed to antigenic stimuli, the number of these memory T cells increases. Natural killer (NK) cells are found in small numbers in the peripheral blood of neonates. These cells are also functionally immature in that they produce far lower levels of interferon - gamma upon primary stimulation than do adult NK cells.
Humoral immunity

body are present in the newborn but are functionally deficient. Skin & mucus membranes are broken down easily in the premature infant. Neonates who are ill and/or premature are additionally at risk because of the invasive procedures that breach their physical barriers to infection.
Mortality / Morbidity

The fetus has some preformed immunoglobulin present, primarily acquired through nonspecific placental transfer from the mother. Most of this transfer occurs in late gestation, such that lower levels are found with increasing prematurity. The neonates ability to generate immunoglobulin in response to antigenic stimulation is intact; however, the magnitude of the response is initially decreased, rapidly rising with increasing postnatal age. The neonate is also capable of synthesizing immunoglobulin M (IgM) in utero at 10 weeks gestation; however, IgM levels are generally low at birth, unless the infant was exposed to an infectious agent during the pregnancy, thereby stimulating increased IgM production. Immunoglobulin G (IgG) & immunoglobulin E (IgE) may be synthesized in utero. Most of the IgG is acquired from the mother during late gestation. The neonate may receive immunoglobulin A (IgA) from breastfeeding but does not secrete IgA until 2 - 5 weeks after birth. Response to bacterial polysaccharide antigen is diminished & remains so during the first 2 years of life. Complement protein production can be detected as early as 6 weeks gestation; however, the concentration of the various components of the complement system widely varies among individual neonates. Although some infants have had complement levels comparable with those in adults, deficiencies appear to be greater in the alternative pathway than in the classic pathway. T
Barrier function

The mortality rate in neonatal sepsis may be as high as 50% for infants who are not treated. Infection is a major cause of fatality during the first month of life, contributing to 13 - 15% of all neonatal deaths. In the preterm infant, inflammatory mediators associated with neonatal sepsis may contribute to brain injury & poor neurodevelopmental outcomes.
Age

Premature infants have an increased incidence of sepsis. The incidence of sepsis is significantly higher in infants with very low birth weight (< 1000 g). The risk for death or meningitis from sepsis is higher in infants with low birth weight than in full - term neonates.
History

The physical & chemical barriers to infection in the human

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The most common risk factors associated with early onset neonatal sepsis include maternal group B Streptococcus (GBS) colonization (especially if untreated during labor), premature rupture of membranes (PROM), preterm rupture of membranes, prolonged rupture of membranes, prematurity, maternal urinary tract infection & chorioamnionitis. Other factors associated with or predisposing to early onset neonatal sepsis include low Apgar score (< 6 at 1 or 5 min), maternal fever greater than 38C, maternal urinary tract infection, poor prenatal care, poor maternal nutrition, low socioeconomic status, recurrent abortion, maternal substance abuse, low birth weight, difficult delivery, birth asphyxia, meconium staining & congenital anomalies. Late onset sepsis is associated with the following risk factors : prematurity, central venous catheterization (duration of > 10 d), nasal

cannula or continuous positive airway pressure (CPAP) use, H2 blocker/proton pump inhibitor use & gastrointestinal tract pathology.
Physical

Metabolic signs : Hypoglycemia, hyperglycemia, metabolic

The clinical signs of neonatal sepsis are nonspecific & are associated with characteristics of the causative organism & the bodys response to the invasion. These nonspecific clinical signs of early sepsis syndrome are also associated with other neonatal diseases, such as respiratory distress syndrome (RDS), metabolic disorders, intracranial hemorrhage & a traumatic delivery. The following localizing symptoms are some of the most useful clues to the etiology sepsis : Head & neck infections - Severe headache, neck stiffness, altered mental status, earache, sore throat, sinus pain or tenderness, cervical or submandibular lymphadenopathy Chest & pulmonary infections - Cough (especially if productive), pleuritic chest pain, dyspnea Abdominal & GI infections - Abdominal pain, nausea, vomiting, diarrhea Pelvic & genitourinary infections - Pelvic or flank pain, vaginal or urethral discharge, dysuria, frequency, urgency Bone & soft - tissue infections - Focal pain or tenderness, focal erythema, edema, fluctuance A systematic physical assessment of the infant is best performed in series & should include observation, auscultation & palpation in that order to obtain the most information from the examination. Tachypnea, irregular respirations, moderate retracting, apnea, cyanosis & grunting may be observed. Neonates with intrauterine pneumonia may also be critically ill at birth & require high levels of ventilatory support. The chest radiograph may depict bilateral consolidation or pleural effusions. Cardiac signs : In overwhelming sepsis, an initial early phase characterized by pulmonary hypertension, decreased cardiac output & hypoxemia may occur.
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acidosis & jaundice all are metabolic signs that commonly accompany neonatal sepsis syndrome. The infant has an increased glucose requirement because of sepsis. Neurologic signs : Meningitis is the common manifestation of infection of the CNS.
Hematologic signs

Thrombocytopenia with counts less than 100, 000 may occur in neonatal sepsis in response to the cellular products of the microorganisms. Normal WBC counts may be initially observed in as many as 50% of cases of culture - proven sepsis. Infants who are not infected may also demonstrate abnormal WBC counts related to the stress of delivery or several other factors. Neutropenia is observed in sepsis, maternal hypertension, severe perinatal asphyxia & periventricular or intraventricular hemorrhage. Disseminated intravascular coagulation (DIC) can occur in infected infants. GI signs : The intestinal tract can be colonized by organisms in utero or at delivery by swallowing infected amniotic fluid. The immunologic defenses of the intestinal tract are not mature, especially in the preterm infant. The hallmark of severe sepsis & septic shock are changes that occur at the microvascular & cellular level with diffuse activation of inflammatory & coagulation cascades, vasodilation & vascular mal distribution, capillary endothelial leak & dysfunctional utilization of oxygen & nutrients at the cellular level. Fever is a common feature of sepsis. An inquiry should be made about fever onset (abrupt or gradual), duration & maximal temperature. Tachycardia is a common feature of sepsis & indicative of a

Physical

systemic response to stress. Tachycardia is the physiologic mechanism of increasing cardiac output & thus increasing oxygen delivery to tissues. It indicates hypovolemia & the need for intravascular fluid repletion; however, tachycardia often persists in sepsis despite adequate fluid repletion. Tachycardia may also be a result of fever itself. Increased respiratory rate is a common & often underappreciated feature of sepsis. Stimulation of the medullary ventilatory center by endotoxins & other inflammatory mediators has been proposed as a cause. As tissue hypoperfusion ensues, the respiratory rate also increases in order to compensate for metabolic acidosis. Altered mental status is a common feature of sepsis syndromes. It is considered a sign of organ dysfunction & is associated with increased mortality. The physical examination should first involve assessment of the patients general condition, including an assessment of airway, breathing & circulation (ABCs) & mental status. Attention should be paid to skin color & temperature. Pallor, grayish, or mottled skin are signs of poor tissue perfusion seen in septic shock. Skin is often warm in early septic shock as peripheral dilation & increased cardiac output occur (warm shock).

Hypoglycemia Hypoplastic Left Heart Syndrome Meconium Aspiration Syndrome

Laboratory Studies

Urinary Tract Infection

Differential diagnosis

Metabolic Acidosis Necrotizing Enterocolitis Bowel obstruction in the Newborn Osteomyelitis Coarctation of the Aorta Congenital Diaphragmatic Hernia Congenital Lung Malformations Persistent Pulmonary Hypertension Newborn Congenital Pneumonia Pulmonary Hypoplasia Congestive Heart Failure Pulmonary Sequestration Hemolytic Disease of Newborn Respiratory Distress Syndrome Hemorrhagic Disease of Newborn
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Blood, cerebrospinal fluid (CSF) & urine cultures Bacterial culture results should generally reveal the organism of infection within 36 - 48 hours; subsequent initial identification of the organism occurs within 12 - 24 hours of the growth. Urine cultures are most appropriate when investigating late onset sepsis. Blood & CSF cultures are appropriate for early onset & late onset sepsis. A lumbar puncture should be part of the evaluation of an infant with suspected sepsis. A CBC count & differential may be ordered serially to determine changes associated with the infection The CSF findings in infectious neonatal meningitis are an elevated WBC count (predominately PMNs), an elevated protein level, a depressed glucose level & positive culture results. The decrease in glucose is not reflective of serum hypoglycemia. Levels of C - reactive protein (CRP), an acute phase protein associated with tissue injury, are elevated at some point in 50 90% of infants with systemic bacterial infections. CRP levels rise secondary to macrophage, T - cell & adipocyte production of interleukin - 6 (IL - 6). IgM concentration in serum may be helpful in determining the presence of an intrauterine infection, especially if the infection has been present over a period of time.

Imaging studies

Head ultrasonography in neonates with meningitis may reveal evidence of ventriculitis, abnormal parenchymal echogenicities, extracellular fluid & chronic changes.

Serially, head ultrasonography can reveal the progression of complications.

Medical Care

When neonatal sepsis is suspected, treatment should be initiated immediately because of the neonates relative immunosuppression. Begin antibiotics as soon as diagnostic tests are performed. The current approach to treat early onset neonatal sepsis syndrome includes combined intravenous (IV) aminoglycoside & expanded - spectrum penicillin antibiotic therapy. This provides coverage for gram - positive organisms, especially group B Streptococcus (GBS) & gram - negative bacteria, such as E coli. The specific antibiotics to be used are chosen on the basis of maternal history & prevalent trends of organism colonization & antibiotic susceptibility in individual nurseries. o Cephalosporins are attractive in the treatment of nosocomial infection because of their lack of dose - related toxicity & adequate serum & cerebrospinal fluid (CSF) concentration; however, resistance by gram - negative organisms has occurred with their use. Ceftriaxone displaces bilirubin from serum albumin & should be used with caution in infants with significant hyperbilirubinemia. o Aminoglycosides & vancomycin both have the potential to produce ototoxicity & nephrotoxicity & should therefore be used with caution. o Infants with bacterial meningitis often require different dosages of antibiotics & longer courses of treatment. These infants may also require an antimicrobial that has better penetration of the blood - brain barrier to achieve therapeutic drug concentrations in the CSF. o Meningitis complicated by seizures or persistent positive cultures may require extended IV antimicrobial therapy. Chloramphenicol or trimethoprim - sulfamethoxazole has been shown to be effective in the treatment of highly resistant bacterial meningitis. Trimethoprim - sulfamethoxazole should
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not be used if hyperbilirubinemia & kernicterus are of concern in the newborn. IVIG infusion has been a possible therapy for neonatal sepsis to provide type - specific antibodies to improve opsonization & phagocytosis of bacterial organisms & to improve complement activation & chemotaxis of neonatal neutrophils; The infant with sepsis may require treatment aimed at the overwhelming systemic effects of the disease. Cardiopulmonary support & intravenous nutrition may be required during the acute phase of the illness until the infants condition stabilizes. Monitoring of blood pressure, vital signs, hematocrit, platelets & coagulation studies is vital. The need for blood product transfusion including packed RBCs (PRBCs), platelets & fresh frozen plasma (FFP) is not uncommon.

Diet

The neonate may need to be given nothing by mouth (NPO) during the first days of treatment because of gastrointestinal symptoms, feeding intolerance, or poor feeding. Consider parenteral nutrition to ensure that the patients intake of calories, protein, minerals & electrolytes is adequate during this period. Feeding may be restarted via a nasogastric tube with (EBM) extracted breast milk for the infant with serious compromise. For most infants, breast milk is the enteral diet recommended by the AAP.
Activity

The infant with temperature instability needs thermoregulatory support with a radiant warmer or incubator. Once the infant is stable from a cardiopulmonary standpoint, parental contact is important. Some of the antibiotics commonly used to treat neonatal sepsis syndrome include ampicillin, gentamicin, cefotaxime, vancomycin, metronidazole, erythromycin & piperacillin. The choice of antibiotic agents should be based on the specific organisms associated with

sepsis, sensitivities of the bacterial agent & prevalent nosocomial infection trends in the nursery. Viral infections such as herpes & fungal infections can masquerade as bacterial infections.

19
Background

Jaundice is the most common condition that requires medical attention in newborns. The yellow coloration of the skin & sclera in newborns with jaundice is the result of accumulation of unconjugated bilirubin. In most infants, unconjugated hyperbilirubinemia reflects a normal transitional phenomenon. However, in some infants, serum bilirubin levels may excessively rise, which can be cause for concern because unconjugated bilirubin is neurotoxic & can cause death in newborns & lifelong neurologic sequelae in infants who survive (kernicterus). For these reasons, the presence of neonatal jaundice frequently results in diagnostic evaluation. Neonatal jaundice may have first been described in a Chinese textbook 1000 years ago. Medical theses, essays & textbooks from the 18th & 19th centuries contain discussions about the causes & treatment of neonatal jaundice. Several of these texts also describe a lethal course in infants who probably had Rh isoimmunization. In 1875, Orth first described yellow staining of the brain, in a pattern later referred to as kernicterus.
Pathophysiology

Neonatal physiologic jaundice results from simultaneous occurrence of the following 2 phenomena : Bilirubin production is elevated because of increased breakdown of fetal erythrocytes. This is the result of the shortened lifespan of fetal erythrocytes & the higher erythrocyte mass in neonates. Hepatic excretory capacity is low both because of low concentrations of the binding protein ligandin in the hepatocytes & because of low activity of glucuronyl transferase, the enzyme
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responsible for binding bilirubin to glucuronic acid, thus making bilirubin water soluble (conjugation). Bilirubin is produced in the reticuloendothelial system as the end product of heme catabolism & is formed through oxidation reduction reactions. Approximately 75% of bilirubin is derived from hemoglobin, but degradation of myoglobin, cytochromes & catalase also contributes. In the first oxidation step, biliverdin is formed from heme through the action of heme oxygenase, the rate - limiting step in the process, releasing iron & carbon monoxide. The iron is conserved for reuse, whereas carbon monoxide is excreted through the lungs & can be measured in the patients breath to quantify bilirubin production. Next, water - soluble biliverdin is reduced to bilirubin, which, because of the intramolecular hydrogen bonds, is almost insoluble in water in its most common isomeric form (bilirubin IX Z, Z). Because of its hydrophobic nature, unconjugated bilirubin is transported in the plasma tightly bound to albumin. Binding to other proteins & erythrocytes also occurs, but the physiologic role is probably limited. Binding of bilirubin to albumin increases postnatally with age & is reduced in infants who are ill. The presence of endogenous & exogenous binding competitors, such as certain drugs, also decreases the binding affinity of albumin for bilirubin. A minute fraction of unconjugated bilirubin in serum is not bound to albumin. This free bilirubin is able to cross lipid containing membranes, including the blood - brain barrier, leading to neurotoxicity. In fetal life, free bilirubin crosses the placenta, apparently by passive diffusion & excretion of bilirubin from the fetus occurs primarily through the maternal organism. When it reaches the liver, bilirubin is transported into liver cells, where it binds to ligandin. Uptake of bilirubin into hepatocytes increases with increasing ligandin concentrations. Ligandin concentrations are low at birth but rapidly increase over the first few weeks of life. Ligandin concentrations may be increased by the administration of pharmacologic agents such as phenobarbital.

Bilirubin is bound to glucuronic acid (conjugated) in the hepatocyte endoplasmic reticulum in a reaction catalyzed by uridine diphosphoglucuronyltransferase (UDPGT). Monoconjugates are formed first & predominate in the newborn. Diconjugates appear to be formed at the cell membrane & may require the presence of the UDPGT tetramer. Bilirubin conjugation is biologically critical because it transforms a water - insoluble bilirubin molecule into a water - soluble molecule. Water - solubility allows conjugated bilirubin to be excreted into bile. UDPGT activity is low at birth but increases to adult values by age 4 - 8 weeks. In addition, certain drugs (Phenobarbital, dexamethasone & clofibrate) can be administered to increase UDPGT activity. Infants who have Gilbert syndrome or who are compound heterozygotes for the Gilbert promoter & structural mutations of the UDPGT1A1 coding region are at an increased risk of significant hyperbilirubinemia. Interactions between the Gilbert genotype & hemolytic anemias such as glucose - 6 - phosphatase dehydrogenase (G - 6 - PD) deficiency, hereditary spherocytosis, or ABO hemolytic disease also appear to increase the risk of severe neonatal jaundice. Further, the observation of jaundice in some infants with hypertrophic pyloric stenosis may also be related to a Gilbert - type variant. Genetic polymorphism for the organic anion transporter protein OATP - 2 correlates with a 3 - fold increased risk for developing marked neonatal jaundice. Combination of the OATP - 2 gene polymorphism with a variant UDPGT1A1 gene further increases this risk to 22 - fold. Studies also suggest that polymorphisms in the gene for glutathione - S - transferase (ligandin) may contribute to higher levels of total serum bilirubin. Thus, some interindividual variations in the course & severity of neonatal jaundice may be explained genetically. As the impact of these genetic variants is more fully understood, development of a genetic test panel for risk of severe and/or prolonged neonatal jaundice may become feasible.
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Once excreted into bile & transferred to the intestines, bilirubin is eventually reduced to colorless tetrapyrroles by microbes in the colon. However, some deconjugation occurs in the proximal small intestine through the action of B - glucuronidases located in the brush border. This unconjugated bilirubin can be reabsorbed into the circulation, increasing the total plasma bilirubin pool. This cycle of uptake, conjugation, excretion, deconjugation & reabsorption is termed enterohepatic circulation. The process may be extensive in the neonate, partly because nutrient intake is limited in the first days of life, prolonging the intestinal transit time. In mother - infant dyads who are experiencing difficulties with the establishment of breast feeding, inadequate fluid & nutrient intake often leads to significant postnatal weight loss in the infant. Such infants have an increased risk of developing jaundice through increased enterohepatic circulation, as described above. This phenomenon is often referred to as breastfeeding jaundice & is different from the breast milk jaundice described below. Certain factors present in the breast milk of some mothers may also contribute to increased enterohepatic circulation of bilirubin (breast milk jaundice). - glucuronidase may play a role by uncoupling bilirubin from its binding to glucuronic acid, thus making it available for reabsorption. Data suggest that the risk of breast milk jaundice is significantly increased in infants who have genetic polymorphisms in the coding sequences of the UDPGT1A1 or OATP2 genes. Although the mechanism that causes this phenomenon is not yet agreed on, evidence suggests that supplementation with certain breast milk substitutes may reduce the degree of breast milk jaundice (see other therapies). Neonatal jaundice, although a normal transitional phenomenon in most infants, can occasionally become more pronounced. Blood group incompatibilities (e.g. Rh, ABO) may increase bilirubin production through increased hemolysis. Historically, Rh isoimmunization was an important cause of severe jaundice, often resulting in the development of kernicterus. Although this condition

has become relatively rare in industrialized countries following the use of Rh prophylaxis in Rh - negative women, Rh isoimmunization remains common in developing countries. Nonimmune hemolytic disorders (spherocytosis, G - 6 - PD deficiency) may also cause increased jaundice & increased hemolysis appears to have been present in some of the infants reported to have developed kernicterus in the United States in the past 10 - 15 years. The possible interaction between such conditions & genetic variants of the Gilbert & UDPGT1A1 genes, as well as genetic variants of several other proteins & enzymes involved in bilirubin metabolism, is discussed above. These discoveries also highlight the challenges involved in the common use of the terms physiologic jaundice & pathologic jaundice. Although physiologic jaundice is a helpful concept from a didactic perspective, applying it to an actual neonate with jaundice is more difficult. Consider the following metaphor : Think of total serum bilirubin in neonatal jaundice as a mountain covered by a glacier. If a measurement of the height of the mountain is taken when standing on the summit, the amount of rock & the amount of ice that comprise this measurement is unclear. The same is true for many total serum bilirubin values obtained in neonatal jaundice. An underpinning of physiologic processes & pathological process (e.g. Rhesus incompatibility) may clearly contribute to the measurement. However, how much of the measured total value comes from each of these components is unclear. Also, because genetic variants in bilirubin metabolism are only exceptionally pursued in the diagnostic work up of infants with jaundice, their possible contribution to the measured total serum bilirubin is usually unknown.
Mortality / Morbidity

Risk of developing significant neonatal jaundice is higher in male infants. This does not appear to be related to bilirubin production rates, which are similar to those in female infants.
Age

The risk of significant neonatal jaundice is inversely proportional to gestational age.

History Presentation & duration of neonatal jaundice

Typically, presentation is on the second or third day of life. Jaundice that is visible during the first 24 hours of life is likely to be non physiologic; further evaluation is suggested. Infants who present with jaundice after 3 - 4 days of life may also require closer scrutiny & monitoring. In infants with severe jaundice or jaundice that continues beyond the first 1 - 2 weeks of life, the results of the newborn metabolic screen should be checked for galactosemia & congenital hypothyroidism, further family history should be explored (see below), the infants weight curve should be evaluated, the mothers impressions as far as adequacy of breastfeeding should be elicited & the stool color should be assessed. Previous sibling with jaundice in the neonatal period, particularly if the jaundice required treatment Other family members with jaundice or known family history of Gilbert syndrome Anemia, splenectomy, or bile stones in family members or known heredity for hemolytic disorders Liver disease Maternal illness suggestive of viral or other infection Maternal drug intake Delayed cord clamping

Family history

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Death from physiologic neonatal jaundice per se should not occur. Death from kernicterus may occur, particularly in countries with less developed medical care systems.
Sex

History of pregnancy & delivery

Birth trauma with bruising Loss of stool color Breastfeeding Greater than average weight loss Symptoms or signs of hypothyroidism Symptoms or signs of metabolic disease (e.g. galactosemia) Exposure to total parental nutrition

Postnatal history

of phototherapy. Hepatosplenomegaly, petechiae & microcephaly may be associated with hemolytic anemia, sepsis & congenital infections & should trigger a diagnostic evaluation directed towards these diagnoses. Neonatal jaundice may be exacerbated in these situations.
Causes

Physical

Neonatal jaundice first becomes visible in the face & forehead. Identification is aided by pressure on the skin, since blanching reveals the underlying color. Jaundice then gradually becomes visible on the trunk & extremities. This cephalocaudal progression is well described, even in 19th - century medical texts. Jaundice disappears in the opposite direction. The explanation for this phenomenon is not well understood, but both changes in bilirubin - albumin binding related to pH & differences in skin temperature & blood flow have been proposed. This phenomenon is clinically useful because, independent of other factors, visible jaundice in the lower extremities strongly suggests the need to check the bilirubin level, either in the serum or noninvasively via transcutaneous bilirubinometry. In most infants, yellow color is the only finding on physical examination. More intense jaundice may be associated with drowsiness. Brainstem auditory - evoked potentials performed at this time may reveal prolongation of latencies, decreased amplitudes, or both. Overt neurologic findings, such as changes in muscle tone, seizures, or altered cry characteristics, in a significantly jaundiced infant are danger signs & require immediate attention to prevent kernicterus. In the presence of such symptoms or signs, effective phototherapy should commence immediately without waiting for the laboratory test results (see Laboratory Studies). The potential need for exchange transfusion should not preclude the immediate initiation
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Physiologic jaundice is caused by a combination of increased bilirubin production secondary to accelerated destruction of erythrocytes, decreased excretory capacity secondary to low levels of ligandin in hepatocytes & low activity of the bilirubin - conjugating enzyme uridine diphosphoglucuronyltransferase (UDPGT). Pathologic neonatal jaundice occurs when additional factors accompany the basic mechanisms described above. Examples include immune or nonimmune hemolytic anemia, polycythemia & the presence of bruising or other extravasation of blood. Decreased clearance of bilirubin may play a role in breast feeding jaundice, breast milk jaundice & in several metabolic & endocrine disorders.
Risk factors include Race : Incidence is higher in East Asians & American Indians

& is lower in African Americans. Geography : Incidence is higher in populations living at high altitudes. Greeks living in Greece have a higher incidence than those living outside of Greece. Genetics & familial risk : Incidence is higher in infants with siblings who had significant neonatal jaundice & particularly in infants whose older siblings were treated for neonatal jaundice. Incidence is also higher in infants with mutations/ polymorphisms in the genes that code for enzymes & proteins involved in bilirubin metabolism & in infants with homozygous or heterozygous glucose - 6 - phosphatase dehydrogenase (G 6 - PD) deficiency & other hereditary hemolytic anemias. Combinations of such genetic variants appear to exacerbate neonatal jaundice.

Nutrition : Incidence is higher in infants who are breastfed or

who receive inadequate nutrition. The mechanism for this phenomenon may not be fully understood. However, when inadequate feeding volume is involved, increased enterohepatic circulation of bilirubin probably contributes to prolonged jaundice. Recent data have shown that breast milk jaundice correlates with higher levels of epidermal growth factor, both in breast milk & in infants serum. Data suggest that the difference between breastfed & formula - fed infants may be less pronounced with some modern formulas. However, formulas containing protein hydrolysates have been shown to promote bilirubin excretion. Maternal factors : Infants of mothers with diabetes have higher incidence. Use of some drugs may increase the incidence, whereas others decrease the incidence. Birthweight & gestational age : Incidence is higher in premature infants & in infants with low birthweight.
Congenital infection

Bowel atresia Hypertrophic pyloric stenosis Choledochal cyst Conjugated hyperbilirubinemia Crigler - Najjar syndrome Arias syndrome Gilbert syndrome Immune hemolytic anemia Nonimmune hemolytic anemia Congenital infections with cytomegalovirus or toxoplasmosis The following studies are indicated in neonatal jaundice :

Laboratory Studies Bilirubin measurement may include the following :

Differential Diagnoses

Biliary Atresia

Breast Milk Jaundice Cholestasis Cytomegalovirus Infection Dubin - Johnson Syndrome Duodenal Atresia

Galactose - 1 - Phosphate Uridyltransferase Deficiency (Galactosemia) Hemolytic Disease of Newborn Hepatitis B Hypothyroidism

o o o o o
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Other problems to be considered

Certain conditions may cause non - physiologic jaundice. In these infants, a baseline physiologic jaundice most likely occurs, which is then exaggerated, for example, by increased enterohepatic circulation in bowel atresia, bile stasis in choledochal cyst, or increased bilirubin production in hemolytic anemias. Such conditions include the following :

Transcutaneous bilirubinometry can be performed using handheld devices that incorporate sophisticated optical algorithms. Use of such devices has been shown to reduce the need for blood sampling in infants with jaundice. However, they cannot be used to monitor the progress of phototherapy. Usually, a total serum bilirubin level test is the only one required in an infant with moderate jaundice who presents on the typical second or third day of life without a history & physical findings suggestive of a pathologic process. Measurement of bilirubin fractions (conjugated vs unconjugated) in serum is not usually required in infants who present as described above. Additional studies may be indicated in the following situations : Infants who present with jaundice on the first or after the third day of life Infants who are anemic at birth Infants who otherwise appear ill Infants in whom serum bilirubin levels are elevated enough to trigger treatment Infants in whom significant jaundice persists beyond the first 2 weeks of life

o o

o o o o

o o o

Infants in whom family, maternal, pregnancy, or case histories suggest the possibility of a pathologic process Infants in whom physical examination reveals findings not explained by simple physiologic hyperbilirubinemia In addition to total serum bilirubin levels, other suggested studies may include the following, particularly if the rate of rise or the absolute bilirubin concentration is approaching the need for phototherapy : Blood type & Rh determination in mother & infant Direct antiglobulin test (DAT) in the infant (direct Coombs test) Hemoglobin & hematocrit values Serum albumin levels : This appears to be a useful adjunct in evaluating risk of toxicity levels because albumin binds bilirubin in a ratio of 1 : 1 at the primary high - affinity binding site. Peripheral blood film for erythrocyte morphology Reticulocyte count Conjugated bilirubin levels : Measuring bilirubin fractions may be indicated in the circumstances described above. Note that direct bilirubin measurements are often inaccurate, are subject to significant inter laboratory & intra laboratory variation & are generally not a sensitive tool for diagnosing cholestasis unless repeated measurements confirm the presence of an elevated conjugated bilirubin. Liver function tests : Aspartate aminotransferase (ASAT or SGOT) & alanine aminotransferase (ALAT or SGPT) levels are elevated in hepatocellular disease. Alkaline phosphatase & - glutamyltransferase (GGT) levels are often elevated in cholestatic disease. A - GT/ALAT ratio of more than 1 is strongly suggestive of biliary obstruction. However, it does not distinguish between intrahepatic & extrahepatic cholestasis. Tests for viral and/or parasitic infection : These may be indicated in infants with hepatosplenomegaly, petechiae,
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o o

thrombocytopenia, or other evidence of hepatocellular disease. Reducing substance in urine : This is a useful screening test for galactosemia, provided the infant has received sufficient quantities of milk. Blood gas measurements : The risk of bilirubin CNS toxicity is increased in acidosis, particularly respiratory acidosis. Thyroid function tests

Imaging Studies

Ultrasonography : Ultrasonography of the liver & bile ducts is warranted in infants with laboratory or clinical signs of cholestatic disease. Radionuclide scanning : A radionuclide liver scan for uptake of hepato - iminodiacetic acid (HIDA) is indicated if extrahepatic biliary atresia is suspected. At the authors institution, patients are pretreated with phenobarbital 5 mg/kg/d for 3 - 4 days before performing the scan.
Medical Care

1) 2) 3)
1)

Phototherapy Intravenous immune globulin (IVIG) & Exchange transfusion are the most widely used therapeutic modalities in infants with neonatal jaundice.
Phototherapy

Phototherapy is the primary treatment in neonates with unconjugated hyperbilirubinemia. This therapeutic principle was discovered rather serendipitously in England in the 1950s & is now arguably the most widespread therapy of any kind (excluding prophylactic treatments) used in newborns. Phototherapy is effective because 3 reactions can occur when bilirubin is exposed to light, as follows : Initially, photo - oxidation was believed to be responsible for the beneficial effect of phototherapy. However, although bilirubin is bleached through the action of light, the process is slow & is now believed to contribute only minimally to the therapeutic effect of phototherapy.

Configurational isomerization is a very rapid process that changes some of the predominant 4Z, 15Z bilirubin isomers to water - soluble isomers in which one or both of the intramolecular bonds are opened (E, Z; Z, E; or E, E). In human infants, the 4Z, 15E isomer predominates, and, at equilibrium conditions, the isomer constitutes about 20 - 25% of circulating bilirubin after a few hours of phototherapy. This proportion is not significantly influenced by the intensity of light. Data have shown that formation of photo isomers is significant after as little as 15 minutes of phototherapy. Structural isomerization consists of intramolecular cyclization, resulting in the formation of lumirubin. This process is enhanced by increasing the intensity of light. During phototherapy, lumirubin may constitute 2 - 6% of the total serum bilirubin concentration. The photo - isomers of bilirubin are excreted in bile and, to some extent, in urine. The half - life of lumirubin in serum is much shorter than that in E isomers & lumirubin is the primary pigment found in bile during phototherapy. Bear in mind when initiating phototherapy that lowering of the total serum bilirubin concentration may be only part of the therapeutic benefit. Because photo - isomers, by virtue of their water - soluble nature, should not be able to cross the blood - brain barrier, phototherapy may reduce the risk of bilirubin - induced neurotoxicity as soon as the lights are turned on. At any given total serum bilirubin concentration, the presence of 20 - 25% of photo - isomers means that only 75 - 80% of the total bilirubin may be present in a form that can enter the brain. Please note that although theoretically coherent, no experimental data support this speculation. Phototherapy can be administered in a number of ways. To understand the benefits & limitations of the various approaches, some basic principles regarding wavelength & types of light are discussed below with comments & suggestions regarding each system. First, wavelength must be considered. Bilirubin absorbs light
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primarily around 450 - 460 nm. However, the ability of light to penetrate skin is also important; longer wavelengths penetrate better. Thus, lamps with output predominantly in the blue region of the spectrum (460 - 490 nm) are probably most effective. In practice, light is used in the white, blue, turquoise & green wavelengths. Second, a dose - response relationship may be observed between the amount of irradiation & reduction in serum bilirubin up to an irradiation level of 30 - 40 W/cm2/nm. Many older phototherapy units deliver much less energy, some at or near the minimally effective level, which appears to be approximately 6 W/cm2/nm. On the other hand, newer phototherapy units, when properly configured & with the use of reflecting blanket & curtains may deliver light energy above the 40 W/cm2/nm suggested to be the saturation level. Third, the energy delivered to the infants skin decreases with increasing distance between the infant & the light source. This distance should not be greater than 50 cm (20 in) & can be less (down to 10 cm) provided the infants temperature is monitored. Fourth, the efficiency of phototherapy depends on the amount of bilirubin that is irradiated. Irradiating a large skin surface area is more efficient than irradiating a small area & the efficiency of phototherapy increases with serum bilirubin concentration. Fifth, the nature & character of the light source may affect energy delivery. Irradiation levels using quartz halide spotlights are maximal at the center of the circle of light & decrease sharply towards the perimeter of the circle. Large infants & infants who can move away from the circles center may receive less efficient phototherapy. Although green light theoretically penetrates the skin better, it has not been shown unequivocally to be more efficient in clinical use than blue or white light. Because green light makes babies look sick & is unpleasant to work in, green light has not gained widespread acceptance. Blue fluorescent tubes are widely used for phototherapy. Narrow - spectrum blue lamps (special blue) appear to work best, while ordinary blue fluorescent lamps are probably equivalent to standard

white daylight lamps. Blue lights may cause discomfort in hospital staff members, which can be ameliorated by mixing blue & white tubes in the phototherapy unit. White (daylight) fluorescent tubes are less efficient than special blue lamps; however, decreasing the distance between infants & lamps can compensate for the lower efficiency. Use of reflecting materials also helps. Thus, in developing countries where the cost of special blue lamps may be prohibitive, efficient phototherapy is accomplished with white lamps. White quartz lamps are an integral part of some radiant warmers & incubators. They have a significant blue component in the light spectrum. When used as spotlights, the energy field is strongly focused towards the center, with significantly less energy delivered at the perimeter, as discussed above. Quartz lamps are also used in single or double banks of 3 - 4 bulbs attached to the overhead heat source of some radiant warmers. The energy field delivered by these is much more homogeneous than that of spotlights & the energy output is reasonably high. However, because the lamps are fixed to the overhead heater unit, the ability to increase energy delivery by moving lights closer to infants is limited. Fiberoptic light is also used in phototherapy units. These units deliver high energy levels, but to a limited surface area. Efficiency may be comparable to that of conventional low - output overhead phototherapy units but not to that of overhead units used with maximal output. Drawbacks of fiberoptic phototherapy units include noise from the fan in the light source & decrease of delivered energy with aging and/or breakage of the optic fibers. Advantages include the following Low risk of overheating the infant No need for eye shields Ability to deliver phototherapy with the infant in a bassinet next to the mothers bed Simple deployment for home phototherapy The possibility of irradiating a large surface area when combined with conventional overhead phototherapy units
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(double/triple phototherapy) Double & triple phototherapy, which implies the concurrent use of 2 or 3 phototherapy units to treat the same patient, has often been used in the treatment of infants with very high levels of serum bilirubin. The studies that appeared to show a benefit with this approach were performed with old, relatively low - yield phototherapy units. Newer phototherapy units provide much higher levels of irradiance, which may in fact be close to the apparent saturation level of bilirubin photoisomerization. Whether double or triple phototherapy also confers a benefit with the newer units has not been tested in systematic trials.
Indications for phototherapy

The purpose of treating neonatal jaundice is to avoid neurotoxicity. Thus, indications for treatment have been based on clinical studies of infants who developed kernicterus. Historical data, much of which was derived from infants with hemolytic jaundice, appeared to suggest that total serum bilirubin levels greater than 350 mol/L (20 mg/dL) were associated with increased risk of neurotoxicity, at least in full term infants. As treatment of premature infants became more widespread & increasingly successful during the last half of the 20th century, autopsy findings & follow - up data suggested that immature infants were at risk of bilirubin encephalopathy at lower total serum bilirubin levels than mature infants. Treatment was initiated at lower levels for these infants. Until the 1940s, a truly effective treatment was not available. At that time, exchange transfusion was shown to be feasible & was subsequently used in the treatment of Rh - immunized infants with severe anemia, hyperbilirubinemia, or hydrops. However, exchange transfusion is not without risk for the infant & only with the discovery of phototherapy did neonatal jaundice start to become an indication for treatment on a wider scale. Once phototherapy was shown to be a rather innocuous

treatment, lights were turned on at lower serum bilirubin values than those that had triggered exchange transfusion. Key points in the practical execution of phototherapy include maximizing energy delivery & the available surface area. Also consider the following : The infant should be naked except for diapers (use these only if deemed absolutely necessary & cut them to minimum workable size) & the eyes should be covered to reduce risk of retinal damage. Check the distance between the infants skin & the light source. With fluorescent lamps, the distance should be no greater than 50 cm (20 in). This distance may be reduced down to 10 - 20 cm if temperature homeostasis is monitored to reduce the risk of overheating. Note that this does not apply to quartz lamps. Cover the inside of the bassinet with reflecting material; white linen works well. Hang a white curtain around the phototherapy unit & bassinet. These simple expedients can multiply energy delivery by several folds. When using spotlights, ensure that the infant is placed at the center of the circle of light, since photo energy drops off towards the circles perimeter. Observe the infant closely to ensure that the infant doesnt move away from the high - energy area. Spotlights are probably more appropriate for small premature infants than for larger near - term infants. Older data suggested that phototherapy was associated with increased insensible water loss; therefore, many clinicians have routinely added a certain percentage to the infants estimated basic fluid requirements. Newer data suggest that if temperature homeostasis is maintained, fluid loss is not significantly increased by phototherapy. At the authors institution, routine fluid supplementation for infants under phototherapy is no longer recommended. Rather, the infant is monitored for weight loss, urine output & urine specific gravity. Fluid intake is adjusted accordingly. In infants who are orally fed, the preferred
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fluid is milk because it serves as a vehicle to transport bilirubin out of the gut. Timing of follow - up serum bilirubin testing must be individualized. In infants admitted with extreme serum bilirubin values (> 500 mol/L or 30 mg/dL), monitoring should occur every hour or every other hour. Reductions in serum bilirubin values of 85 mol/L/h (5 mg/dL/h) have been documented under such circumstances. In infants with more moderate elevations of serum bilirubin, monitoring every 6 - 12 hours is probably adequate. Expectations regarding efficacy of phototherapy must be tailored to the circumstances. In infants in whom serum bilirubin concentrations are still rising, a significant reduction of the rate of increase may be satisfactory. In infants in whom serum bilirubin concentrations are close to their peak, phototherapy should result in measurable reductions in serum bilirubin levels within a few hours. In general, the higher the starting serum bilirubin concentration, the more dramatic the initial rate of decline. Discontinuation of phototherapy is a matter of judgment & individual circumstances must be taken into consideration. In practice, phototherapy is discontinued when serum bilirubin levels fall 25 - 50 mol/L (1.5 - 3 mg/dL) below the level that triggered the initiation of phototherapy. Serum bilirubin levels may rebound after treatment has been discontinued & follow up tests should be obtained within 6 - 12 hours after discontinuation. Indications for prophylactic phototherapy are debatable. Phototherapy probably serves no purpose in an infant who is not clinically jaundiced. In general, the lower the serum bilirubin level, the less efficient the phototherapy. It seems more rational to apply truly effective phototherapy once serum (and skin) bilirubin has reached levels at which photons may do some good.

Wherever phototherapy is offered as a therapeutic modality, a device for measuring the irradiance delivered by the equipment used should be readily at hand. This assists in configuring the phototherapy set - up to deliver optimal efficiency. Some recommend this routinely, every time phototherapy is initiated & use this as a tool to focus staff attention on maximizing energy delivery. Generally, phototherapy is very safe & may have no serious long - term effects in neonates; however, the following adverse effects & complications have been noted : Insensible water loss may occur, but data suggest that this issue is not as important as previously believed. Rather than instituting blanket increases of fluid supplements to all infants receiving phototherapy, the author recommends fluid supplementation tailored to the infants individual needs, as measured through evaluation of weight curves, urine output, urine specific gravity & fecal water loss. Phototherapy may be associated with loose stools. Increased fecal water loss may create a need for fluid supplementation. Retinal damage has been observed in some animal models during intense phototherapy. In an NICU environment, infants exposed to higher levels of ambient light were found to have an increased risk of retinopathy. Therefore, covering the eyes of infants undergoing phototherapy with eye patches is routine. Care must be taken lest the patches slip & leave the eyes uncovered or occlude one or both nares. The combination of hyperbilirubinemia & phototherapy can produce DNA - strand breakage & other effects on cellular genetic material. In vitro & animal data have not demonstrated any implication for treatment of human neonates. However, because most hospitals use (cut - down) diapers during phototherapy, the issue of gonad shielding may be moot. Skin blood flow is increased during phototherapy, but this effect is less pronounced in modern servo controlled incubators.
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However, redistribution of blood flow may occur in small premature infants. An increased incidence of patent ductus arteriosus (PDA) has been reported in these circumstances. The appropriate treatment of PDA has been reviewed. Hypocalcemia appears to be more common in premature infants under phototherapy lights. This has been suggested to be mediated by altered melatonin metabolism. Concentrations of certain amino acids in total parenteral nutrition solutions subjected to phototherapy may deteriorate. Shield total parenteral nutrition solutions from light as much as possible. Regular maintenance of the equipment is required because accidents have been reported, including burns resulting from a failure to replace UV filters.
Intravenous immune globulin

2)

In recent years, IVIG has been used for numerous immunologically mediated conditions. In the presence of Rh, ABO, or other blood group incompatibilities that cause significant neonatal jaundice, IVIG has been shown to significantly reduce the need for exchange transfusions.
3) Exchange transfusion

Exchange transfusion is indicated for avoiding bilirubin neurotoxicity when other therapeutic modalities have failed or are not sufficient. In addition, the procedure may be indicated in infants with erythroblastosis who present with severe anemia, hydrops, or both, even in the absence of high serum bilirubin levels. Early exchange transfusion has usually been performed because of anemia (cord hemoglobin < 11 g/dL), elevated cord bilirubin level (> 70 mol/L or 4.5 mg/dL), or both. A rapid rate of increase in the serum bilirubin level (> 15 - 20 mol/L /h or 1 mg/dL/h) was an indication for exchange transfusion, as was a more moderate rate of increase (> 8 - 10 mol/L/h or 0.5 mg/dL/h) in the presence of moderate anemia (11 - 13 g/dL). Intensive phototherapy is strongly recommended in preparation for an exchange transfusion. In fact, intensive phototherapy should

be performed on an emergency basis in any infant admitted for pronounced jaundice; do not await laboratory test results in these cases. Phototherapy has minimal side effects, whereas the waiting period for laboratory test results & blood for exchange can take hours & could constitute the difference between intact survival & survival with kernicterus. If phototherapy does not significantly lower serum bilirubin levels, exchange transfusion should be performed. The most common procedure used is push pull method through
the umbilical vein.

Medical treatment

The commonly used type of blood should be withdrawn within 72 hrs. Frozen RBC reconstituted in saline or plasma may also be used. 160 ml/kg blood is usually needed for one exchange transfusion.
Other therapies

In infants with breast milk jaundice, interruption of breastfeeding for 24 - 48 hours & feeding with breast milk substitutes often helps to reduce the bilirubin level. Evidence suggests that the simple expedient of supplementing feeds of breast milk with 5 mL of a breast milk substitute reduces the level & duration of jaundice in breast milkfed infants. Because this latter intervention causes less interference with the establishment of the breastfeeding dyad, the author prefers to use this approach rather than complete interruption of breast feeding in most cases. Oral bilirubin oxidase can reduce serum bilirubin levels, presumably by reducing enterohepatic circulation; however, its use has not gained wide popularity. The same may be said for agar or charcoal feeds, which act by binding bilirubin in the gut. Prophylactic treatment of Rh - negative women with Rh immunoglobulin has significantly decreased the incidence & severity of Rh - hemolytic disease.
Surgical Care

Medications are not usually administered in infants with physiologic neonatal jaundice. However, in certain instances, phenobarbital, an inducer of hepatic bilirubin metabolism, has been used to enhance bilirubin metabolism. Intravenous immunoglobulin (IVIG) at 500 mg/kg has been shown to significantly reduce the need for exchange transfusions in infants with isoimmune hemolytic disease. The mechanism is unknown but may be related to the way the immune system handles red cells that have been coated by antibodies. Published experience is still somewhat limited, but administration of immunoglobulin does not appear to be likely associated with greater risks for the infant than an exchange transfusion. A new therapy currently under development consists of inhibition of bilirubin production through blockage of heme oxygenase. This can be achieved through the use of metal mesoporphyrins & protoporphyrins. Apparently, heme can be directly excreted through the bile; thus, inhibition of heme oxygenase does not result in accumulation of unprocessed heme. This approach may virtually eliminate neonatal jaundice as a clinical problem. However, before the treatment can be applied on a wide scale, important questions regarding the long - term safety of the drugs must be answered.

20
Neonatal conjunctivitis Classification & external resources A newborn with gonococcal ophthalmia neonatorum. Neonatal conjunctivitis, also known as ophthalmia neonatorum,

Surgical care is not indicated in infants with physiologic neonatal jaundice. Surgical therapy is indicated in infants in whom jaundice is caused by bowel or external bile duct atresia.
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is a form of bacterial conjunctivitis contracted by newborns during delivery. The babys eyes are contaminated during passage through the birth canal from a mother infected with either Neisseria gonorrhoeae or Chlamydia trachomatis. Eye drops containing

erythromycin are typically used to prevent the condition. If left untreated it can cause blindness.
Definition

Neonatal conjunctivitis by definition presents during the first month of life. It may be infectious or non infectious.
Cause Non infectious

Conjunctiva shows hyperaemia & chemosis. Eye lids are usually swollen. Corneal involvement (rare) may occur in herpes simplex opthalmia neonatorum.

Complications

Untreated cases may develop corneal ulceration, which may perforate resulting in corneal opacification & Staphyloma formation.
Treatment

Chemical irritants such as silver nitrate can cause chemical conjunctivitis, usually lasting 24 days. Thus, silver nitrate is no longer in common use. In most instances neomycin & chloramphenicol eye drops are used instead.
Infectious

A) 1) 2)

Many different bacteria & viruses can cause conjunctivitis in the neonate. The two most common causes are N. gonorrhoeae & Chlamydia acquired from the birth canal during delivery. Ophthalmia neonatorum due to gonococci (Neisseria gonorrhoeae) typically manifests in the first 5 days of life & is associated with marked bilateral purulent discharge & local inflammation. In contrast, conjunctivitis secondary to infection with chlamydia (Chlamydia trachomatis) produces conjunctivitis after day 3 of life, but may occur up to 2 weeks after delivery. The discharge is usually more watery in nature (mucopurulent) & less inflamed. Babies infected with chlamydia may develop pneumonitis at a later stage (range 2 weeks 19 weeks after delivery). Infants with chlamydia pneumonitis should be treated with oral erythromycin for 1014 days. Other agents causing Opthalmia neonatorum include Herpes simplex virus (HSV 2), Staphylococcus aureus, Streptococcus haemolyticus, Streptococcus pneumoniae.
Signs & symptoms

3)

B)

Prophylaxis needs antenatal, natal & post natal care. Antenatal measures include thorough care of mother & treatment of genital infections when suspected. Natal measures are of most importance as mostly infection occurs during childbirth. Deliveries should be conducted under hygienic conditions taking all aseptic measures. The newborn babys closed lids should be thoroughly cleansed & dried. Postnatal measures include : Use of 1% tetracycline ointment or 0.5% erythromycin ointment into the eyes of babies immediately after birth Single injection of ceftriaxone 50 mg/kg IM or IV should be given to infants born to mothers with untreated gonococcal infection. Curative treatment as a rule, conjunctival cytology samples & culture sensitivity swabs should be taken before starting treatment Chemical ophthalmia neonatorum is a self - limiting condition & does not require any treatment. Gonococcal ophthalmia neonatorum needs prompt treatment to prevent complications. Saline wash hourly till the discharge is eliminated Bacitracin eye ointment four times per day (Because of resistant strains topical penicillin therapy is not reliable. However in cases with proved penicillin susceptibility, penicillin drops 5000 to 10000 units per ml should be instilled every minute for half

Topical therapy should include

Pain & tenderness in eyeball Conjunctival discharge : purulent, mucoid or mucopurulent depending on the cause.
68

1) 2)

3)

an hour, every five minutes for next half an hour & then half hourly till infection is controlled) If the cornea is involved then atropine sulphate ointment should be applied.

Systemic therapy

Neonates with gonococcal ophthalmia neonatorum should be treated for seven days with one of the following regimens Ceftriaxone 75 100 mg/kg/day IV / IM, QID Cefotaxime 100 150 mg/kg/day IV / IM, 12 hourly Ciprofloxacin 10 20 mg/kg/day / Norfloxacin 10 mg/kg/day Crystalline benzyl penicillin G 50, 000 units (for full - term normal weight babies) or 20, 000 units (for premature or low weight babies) IM twice daily for three days (if penicillin is susceptible) Herpes simplex conjunctivitis is usually a self - limiting disease. Topical antiviral drugs control the infection more effectively & may prevent recurrence.

21
PEM

It includes a range of pathological conditions arising from coincident lack of proteins & calories in varying proportions, occurring most frequently in infants & young children, associated with infections. Malnutrition includes both overnutrition & undernutrition but PEM is mainly related to under nutrition. Primary malnutrition results from inadequate food intake & secondary malnutrition results from defective absorption or increased nutrient loss Protein - energy malnutrition (PEM) compromises a group of related disorders that include marasmus, kwashiorkor & intermediate states of Marasmic - Kwashiorkor. The term Marasmus is derived from the Greek word marasmus, which means withering or wasting. Marasmus involves
69

inadequate intake of protein & calories & is characterized by emaciation. It is associated with the early abandonment or failure of breast - feeding. Infections, especially infantile gastroenteritis may then develop & worsen the malnutrition. The term Kwashiorkor is taken from the Ga language of Ghana & means the sickness of the weaning. Edema is characteristic of kwashiorkor but is absent in marasmus. Studies suggest that marasmus represents an adaptive response to starvation, whereas kwashiorkor represents a maladaptive response to starvation. Children may present with a mixed picture of marasmus & kwashiorkor & children may present with milder forms of malnutrition. For this reason, Jelliffe suggested the term protein - calorie (energy) malnutrition to include both entities. Patients with protein - energy malnutrition may also have deficiencies of vitamins, essential fatty acids & trace elements. If there is a shortage of energy requirements from protein or non - protein sources, it may result in Protein Energy Malnutrition (PEM). The extent of the shortage will decide the severity of the condition. If a childs diet has excessive non - protein calories from starch or sugar, but is deficient in total protein & essential amino acids, the child may develop kwashiorkor. Severe inadequacy of energy & nutrients causes total exhaustion from malnutrition, especially in children, leading to marasmus. Worldwide, the most common cause of malnutrition is inadequate food intake. Preschool - aged children in developing countries are often at risk for malnutrition because of their dependence on others for food, increased protein & energy requirements, immature immune systems causing a greater susceptibility to infection

Etiology of PEM

& exposure to non hygienic conditions.

Pathophysiology

In general, marasmus is an insufficient energy intake to match the bodys requirements. As a result, the body draws on its own stores, resulting in emaciation. In kwashiorkor, adequate carbohydrate consumption & decreased protein intake leads to decreased synthesis of visceral proteins. The resulting decrease in albumin causes dependent edema (swelling of the feet, etc.) & the impaired B - lipoprotein synthesis produces fatty liver. Impaired synthesis of B - lipoprotein produces a fatty liver. Protein - energy malnutrition also involves an inadequate intake of many essential nutrients. Serum levels of zinc correlate closely with the presence of edema, stunting of growth & severe wasting. The classic mosaic skin & flaky pain dermatosis of kwashiorkor bears considerable resemblance to the skin changes of acrodermatitis enteropathica, the dermatosis of zinc deficiency. Marasmus most commonly occurs in children younger than 5 years. This period is characterized by increased energy requirements & increased susceptibility to viral & bacterial infections. Weaning (the gradual deprivation of breast milk & the commencement of nourishment with other food) occurs during this high - risk period. Weaning is affected by geography, economy, hygiene, public health, culture & dietetics. It can be ineffective when the foods introduced provide inadequate nutrients, when the food & water are contaminated, when the access to health care is inadequate, and/or when the patient cannot access or purchase proper nourishment. Low intake of calories or an inability to absorb calories is the
70

key factor in the development of kwashiorkor. In children, the findings of poor weight gain or weight loss; slowing of linear growth; & behavioral changes, such as irritability, apathy, decreased social responsiveness, anxiety & attention deficit may indicate protein - energy malnutrition. In particular, the child is apathetic when undisturbed but irritable when picked up. Kwashiorkor characteristically affects children who are being weaned. Signs include diarrhea & psychomotor changes. Patients with protein - energy malnutrition can also present with nonhealing wounds. This may signify a catabolic process that requires nutritional intervention.
Pathologic differentiation Adaptation in marasmus 1) Diet

Age

Kwashiorkor is mainly due to protein malnutrition with relative excess of energy. Marasmus is mainly due to undernutrition of energy.
Causes of low food intake

2)

Poverty Ignorance Inappropriate feeding - certain foods are not accepted culturallymeat, fish Prolonged breast feeding above 2 yrs of age without weaning Breast feeding stopped early i.e. before 6 mt. Over diluted top feeds Anorexia due to mental causes & infections. Women & girl children eat last & the least Restriction of feeds during certain illness.
Infections

Social factors

History

Like pneumonia, diarrhea, malaria, measles, whooping cough, tuberculosis leads to anorexia, fever (negative nitrogen balance)


3)

parasitic infections. Diarrhea & dysentery cause malabsorption.

Congenital defects

Like cleft lip/palate, TOF tracheo - oesophageal fistula, PS pulmonary stenosis.

4) 5) Pre - term & IUGR

These babies tend to be malnourished if proper care is not taken.

Secondary to illness

Inborn errors of metabolism, liver cirrhosis, hepatitis, CHD congenital heart diseases, asthma, bronchiectasis, diabetes mellitus, growth hormone deficiency, malignancies.
Spectrum of PEM 1) Mild to moderate

inconsistent cutaneous findings include fine, brittle hair; alopecia; impaired growth; & fissuring of the nails. Delayed milestones may be present. Failure to gain weight & height. Metabolically active brown fat is wasted first. Buccal fat is last to be wasted. Child is generally alert but irritable & has voracious appetite. In protein - energy malnutrition, more hairs are in the telogen (resting) phase than in the anagen (active) phase, a reverse of normal. Occasionally, as in anorexia nervosa, marked growth of lanugo hair is noted.
2) Kwashiorkor (oedematous PEM)

These children are adapted to fulfill the deficit to some extent. Energy is conserved by decreasing the physical activity The weight is reduced & looks disproportionate with long body, thin limbs & large head. As nutritional deficiency prolongs for longer period with infections, the child leads to severe forms of PEM i.e. marasmus & kwashiorkor.
Marasmus (non oedematous PEM)

2)

Worst form of PEM 3 essential features - Markedly retarded growth Psychomotor changes Oedema Muscles of upper limb are wasted but lower limbs appear swollen Wasting is masked by well preserved subcutaneous tissue & edema. oedema is clinical feature of increased extracellular water volume Hypoalbuminemia Retention of water & sodium due to increased capillary permeability due to infections & hyperkalemia. Free radical induced damage to cell membranes. If ascites is present abdominal T. B & liver dysfunction must be ruled out Mental changes previously irritable child becomes lethargic. Mental changes are due to brain edema, electrolyte imbalance, neurotransmitter imbalance. Return of social smile is early sign of recovery. Regression of milestones may occur.

Marasmic infants show hunger, gross loss of weight, growth retardation & wasting of subcutaneous fat & muscle. It is the commonest type of PEM. Characterized by emaciation, marked stunting & no edema. Sunken eyes. flabby & hypotonic muscles With marked loss of subcutaneous fat & muscle wasting. Presence of skin folds over buttocks & thighs. The skin is xerotic, wrinkled & loose. Monkey facies /old man/wise man look secondary to a loss of buccal fat pads is characteristic of this disorder. Marasmus may have no clinical dermatosis. However,
71

Causes

1) 2) 3)

Moon facies Child typically presents with a failure to thrive Swollen abdomen (potbelly), and A fatty liver. Skin changes are characteristic & progress over a few days. Crazy pavement dermatosis - The skin becomes dark, dry & then splits open when stretched, revealing pale areas between the cracks. This feature is seen especially over extensor surfaces. In contrast to pellagra, these changes seldom occur on sun exposed skin. Flaky paint dermatosis peeling of skin like old paint flaking off the wall is pathognomic of kwashiorkor. Marbalisation soft & shiny skin with marble like feeling Depigmentation of hair causes it to be reddish yellow to white. Curly hair becomes straightened. Flag sign due to periods of poor nutrition & optimum nutrition, alternating bands of pale & dark hair may occur. Also, hairs become dry, lusterless, sparse & brittle; they can be pulled out easily. Temporal recession & hair loss from the back of the head occur, likely secondary to pressure when the child lies down. In some cases, loss of hair can be extreme. Hair can also become softer & finer & appear unruly. The eyelashes can undergo the same change, having a so - called
Broomstick appearance.

The dermatitis manifests in sun - exposed areas, including the back, neck (Casal necklace), face & dorsum of the hands (gauntlet of pellagra) initially as painful erythema & itching. Protein - energy malnutrition is also associated with an increased likelihood of calciphylaxis, a small vessel vasculopathy involving mural calcification with intimal proliferation, fibrosis & thrombosis.

Prognosis

Mortality varies between 15 & 40%. Death in the first days of treatment is usually due to electrolyte imbalance, infection, hypothermia (severe decrease in body temperature), or heart failure. Long - term effects of malnutrition in childhood are not fully understood. With adequate treatment the liver probably recovers fully without subsequent damage. Immunity is poor during the acute phase of the disease, but is restored when the childs condition improves. Behavioral development may be markedly retarded in the severely malnourished child. The degree of mental impairment is related to the duration of malnutrition & age of onset. An infant with marasmus is affected most severely than a child with kwashiorkor. A mild degree of retardation may be present until the school going age.
Comparison between marasmus & Kwashiorkor Marasmus Appearance Kwashiorkor

Nail plates are thin & soft & may be fissured or ridged. Atrophy of the papillae on the tongue, angular stomatitis, xerophthalmia & cheilosis can occur. Niacin deficiency clinically manifests as pellagra (i.e. dermatitis, dementia, diarrhea) in advanced cases Hepatomegaly is constant finding in Kwashiorkor. Due to excess lipolysis & mobilization of fat into the liver along with deficiency of b lipoproteins to transport fat out of liver. It is reversible & does not lead to cirrhosis.
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Old man look, prominent bony parts, generalized wasting Commonly infants < 60% ++ Common Nil Nil/mild

Age Weight Growth retardation Prevalence Oedema Apathy

Moon face, upper limb wasted, oedema on dependant parts 1 - 5 yrs 60 - 80% + Rare ++ ++

Mental status Appetite Hair changes Skin changes Fatty liver Infections Sr. protein, albumin Anabolism Catabolism Prognosis

Alert Voracious Nil/mild Nil/mild + + Low / normal + ++ Good

Irritable Poor + + ++ ++ Very low Very low + Poor/guarded

2) 3) a)

feeding, weaning, diet during diseased state & present diet should be taken in consideration. This overall assessment is then compared with RDA (recommended dietary allowances)
Clinical features

Clinically observed symptoms & signs are seen.

Anthropometry

Most reliable & practical method.

Age dependant anthropometry

Grading of PEM 1) IAP classification - Grades % of standard wt. for age

I) II) III) IV)

2)

I) II) III)
3)

I) II) III) IV)

71 - 80 % 61 - 70 % 51 - 60 % 50 % If oedema is present, K is added to the grade. Gomez classification - Grades % of standard wt. for age 76 - 90 % 61 - 75 % < 60 % Udanis classification - Grades loss of fat from Buttocks Axilla / groin Abdomen, chest, back Buccal pad of fat. Following parameters are used Dietary factors 2) Clinical features Anthropometry 4) Biochemical parameters Morphological features 6) Radiological features Vital statics
Dietary factors

Weight, height & MAC are compared with reference standards. Weight for age, height for age & weight for height are interpreted. The 50 th percentile is taken as the expected weight or 100%.

Height

It is measured with stadiometer in children & with infantometer for age < 2 yrs.
Classification of stunting (waterlow)

Height for age grade > 95 % normal 90 - 95 % I degree stunting 85 - 90 % 2 degree < 85 % 3
Classification of wasting (waterlow) Weight for height interpretation

Assessment of nutritional status

1) 3) 5) 7)
1)

> 90 % 80 - 90 % 70 - 80 % < 70 %
Wt. (kg)

normal 1st degree wasting 2nd degree wasting 3rd degree wasting
Age in mts+9

infant

Ht. (cm)
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1 - 6 yrs 7 - 12 yrs. 2 - 12 yrs

Age in yrs 2 + 8 Age in yrs 7 5

An overall assessment starting right from breast feeding, initial

Laboratory Studies

o o
o o o o o o

The WHO recommends the following laboratory tests : Blood glucose Examination of blood smears by microscopy or direct detection testing Hemoglobin Urine examination & culture Stool examination by microscopy for ova & parasites Serum albumin HIV test (This test must be accompanied by counseling of the childs parents & strict confidentiality should be maintained.) Electrolytes Significant findings in kwashiorkor include hypoalbuminemia (10 - 25 g/L), hypoproteinemia (transferrin, essential amino acids, lipoprotein) & hypoglycemia. Plasma cortisol & growth hormone levels are high, but insulin secretion & insulinlike growth factor levels are decreased. The percentage of body water & extracellular water is increased. Electrolytes, especially potassium & magnesium, are depleted. Levels of some enzymes (including lactase) are decreased & circulating lipid levels (especially cholesterol) are low. Ketonuria occurs & protein - energy malnutrition may cause a decrease in the urinary excretion of urea because of decreased protein intake. In both kwashiorkor & marasmus, iron deficiency anemia & metabolic acidosis are present. Urinary excretion of hydroxyproline is diminished, reflecting impaired growth & wound healing. Increased urinary 3 methylhistidine is a reflection of muscle breakdown & can be seen in marasmus. Malnutrition also causes immunosuppression, which may result in false - negative tuberculin skin test results & the subsequent failure to accurately assess for tuberculosis.
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Detailed dietary history, growth measurements, body mass index (BMI) & a complete physical examination are indicated. Sensitive measures of nutritional deficiency in children include height - for - age or weight - for - height measurements less than 95% & 90% of expected, respectively, or greater than 2 standard deviations below the mean for age. In children older than 2 years, growth of less than 5 cm/y may also be an indication of deficiency.

Medical Care Treatment

Other Tests

A doctors aim will be to restore & maintain fluid & electrolyte balance. All but the most severely ill respond to a diet based on milk. Supplementary vitamins may be advisable. Small, frequent feedings round the clock are tolerated best in the early stages of recovery. Antibiotics may be prescribed. Unless urgent, treatment of malaria or other parasitic infections will be postponed until the patient is clinically improved. Anemia is usually mild & responds to oral protein, iron & folic acid supplements. In children, the first step in the treatment of protein - energy malnutrition (PEM) is to correct fluid & electrolyte abnormalities & to treat any infections. The most common electrolyte abnormalities are hypokalemia, hypocalcemia, hypophosphatemia & hypomagnesemia. Macronutrient repletion should be started within 48 hours under the supervision of nutrition specialists. The second step in the treatment of protein - energy malnutrition (which may be delayed 24 - 48 h in children) is to supply macronutrients by dietary therapy. Milk - based formulas are the treatment of choice. At the beginning of dietary treatment, patients should be fed ad libitum. After 1 week, intake rates should approach 175 kcal/kg & 4 g/kg of protein for children & 60 kcal/kg & 2 g/kg of protein for adults. A daily multivitamin should also be added.
Indications for hospitalization

1) 2) 3)
I)

Oeedema (Kwashiorkor or marasmic kwashiorkor). Substantial weight deficit, e.g. < 70 % of standard weight for height Or < 60 % of standard weight for age, with : Severe dehydration. Persistent diarrhea & vomiting. Extreme pallor, hypothermia, clinical evidence of shock. Signs of systemic, respiratory tract or other localized infection. Severe anemia (Hb < 5 g dl). Jaundice. Purpura. Persistant loss of appetite.
Initial treatment

(IV), followed by 50 ml of 10% glucose or sucrose by nasogastric (NG) tube. Give broad spectrum antibiotics. Hypothermia (rectal < 35.5 C or the axillary < 35.0 C) : Kangaroo technique Clothe the child well (including the head), cover with a warmed blanket Place a lamp over Treat for hypoglycemia & for serious systemic infection.
Treatment of dehydration A) Oral

Management of severe malnutrition

ReSolMal Amount Duration Route

B)

A) B)
II) III)

Emergency treatment of life threatening complications hypoglycemia & hypothermia; dehydration septic shock vitamin deficiency Severe anemia & heart failure. infections Stabilization to start to feed the child To correct micronutrient deficiency Rehabilitation - To increase feeding to recover lost weight.
Follow up

: One packet + 6 cc KCl + + 100 cc glucose 5 % + 300 cc water : 70 - 100 ml/kg. : 12 hrs. : oral / NGT.

IV fluids

The only indication is circulatory collapse caused by severe dehydration or septic shock. Type : Ringer lactate with 5% glucose or 0.45% NaCl with 5% glucose. Amount : 15 ml/kg. Duration : One hour. If improved; repeat 15 ml/kg over another hour & then shift to ReSolMal by NGT. If not improved; consider septic shock & treat accordingly.
Treatment of septic shock

Emergency Management Hypoglycemia (< 54 mg/dl or 3 mmol/l)

Start treatment on suspicion. If conscious or can be aroused & is able to drink, give 50 ml of 10% glucose or sucrose. If losing consciousness, cannot be aroused or has convulsions, give 5 ml/kg of body weight of sterile 10% glucose intravenously
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Incipient septic shock. The child is usually weak, apathetic & profoundly anorexic, but is neither thirsty nor restless Developed septic shock : dilated rather than constricted superficial veins, tachypnea (> 50 In 2 - 12 months & > 40 in 1 - 5 yrs), grunting, GI bleeding Signs of dehydration, but without a history of watery diarrhoea Hypothermia or hypoglycemia

Management includes

3)

1) 2) 3) 4) 5)

Broad spectrum antibiotics. IV fluid therapy. If no improvement after the 1st hour give blood transfusion or plasma (10 ml/kg over at least 3 hours). If heart failure develops, give diuretics. Steroids, Epinephrine are of no value & should not be used

If the child fails to improve within 48 hours, add chloramphenicol, 25mg/kg IM or IV every 8 hours (or every 6 hours if meningitis is suspected) for 5 days.

Stabilization

Very severe anaemia

haemoglobin concentration is < 4 g/dl or the PCV < 12%, Give 10 ml of packed red cells or whole blood per kg of body weight slowly over 3 hours.
Congestive heart failure

This is usually a complication of overhydration, very severe anaemia, blood or plasma transfusion, or giving a diet with high sodium content The first sign of heart failure is fast breathing 1) Stop all oral intake & IV fluids; No fluid should be given until the heart failure is improved, even if this takes 2448 hours. 2) Give a diuretic IV [furosemide (1 mg/kg). ] 3) Do not give digitalis unless the diagnosis of heart failure is unequivocal (jugular venous pressure is elevated) & the plasma potassium level is normal (digitalis is given at 0.005mg/kg)
Anti - infective treatment

Start feeding : Formula : (F 75) : Each 100 ml : 75 Kcal, 0.9 1.1 gm, 1.3 gm lactose Amount : 130 ml / Kg. Frequency : 2 hours (11 cc / Kg * 12 feeds). Route : Oral; Cup & spoon, better to avoid bottle. NGT; if oral intake < 80 Kcal/ kg/ d. is removed when takes feed orally. If develops abdominal distension during NG feeding, give 2 ml of a 50% solution of magnesium sulfate IM. Vitamins : A large oral dose of vit on day 1 : 50 000 IU (< 6 months), 100 000 IU (6 12 months) & 200000 IU (> 12 months). 5 mg of folic acid orally on day 1 & then 1mg orally per day thereafter.
Vitamins

1)

2)

No apparent signs of infection & no complications : Cotrimoxazole (25 mg of sulfamethoxazole + 5 mg of trimethoprim/kg) orally twice daily for 5 days (0.6 cc / kg/12 hrs). Complications or proved infection : Ampicillin, 50mg/kg IM or IV every 6 hours & gentamicin, 7.5 mg/kg IM or IV once daily for 7 days. Some institutions routinely give malnourished children metronidazole, 7.5 mg/kg every 8 hours for 7 days (Oral : 1 cc / kg / d)
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Vit E : 2.2 mg/ kg / d. Muti - vitamin preparation containing : (for 7 kg BW) Thiamine (vitamin B1) 0.7mg Riboflavin (vitamin B2) 2.0mg Nicotinic acid 10mg Pyridoxine (vitamin B6) 0.7mg Cyanocobalamin (vitamin B12) 1?g Folic acid 0.35mg Ascorbic acid (vitamin C) 100mg Pantothenic acid (vitamin B5) 3mg Biotin 0.1mg Retinol (vitamin A) 1.5mg (5000 IU) Calciferol (vitamin D) 30?g (1200 IU) Vitamin K 40?g
Minerals

Iron supplementation : Postponed. Sodium : Should be restricted to less than 2 mmol/kg/d Potassium : 4.7 mmol/kg/d (up to 7.7 mmol / kd /d) Zinc : 2 mg/kg/d. (1 cc zinc sulphate 2% = 4.5 mg Zn) Mg : 16 - 50mg/kg/d. Calcium : 50 - 80 mg/kg/d. Phosphorus : 60 mg/kg/d Trace elements including : copper (0.3 mg/ kg /d), selenium (4.7?g /kg /d), iodine (12 ?g / kg / d). Lactose intolerance : should be diagnosed only if : Watery diarrhoea promptly after milk - based feeds Acidic faeces (pH < 5.0) Presence of reducing substances in the faeces. Recording food intake If the daily intake < 80 kcal/kg/d the amount should be increased, if more than 100 kcal/kg/d amount of feed should be reduced.
End of initial phase

Assessing progress

The usual weight gain is about 1015 g/kg /d. If < 5 gm/ kg/ d for 3 days = failure to respond
Criteria for transfer to a nutrition rehabilitation centre

Eating well Mental state has improved : smiles, responds to stimuli, interested in surroundings Sits, crawls, stands or walks (depending on age) Normal temperature (36.537.5 C) No vomiting or diarrhoea No oedema Gaining weight : > 5 g/kg of body weight per day for 3 successive days

Failure to respond

When the childs appetite improves & becomes hungry Usually 2 7 days. Complications may take longer, whereas others are hungry from the start
Rehabilitation Formula : (F 100) : Each 100 ml : 100 Kcal, 2.9 gm protein.4.2 gm

Criteria for failure to respond to treatment Criteria Time after admission Primary failure to respond : Failure to regain appetite Day 4 Failure to start to lose oedema Day 4 Oedema still present Day 10 Failure to gain at least 5 g/kg of body weight per day 10 Secondary failure to respond : Failure to gain at least 5 g/kg of body weight per day During rehabilitation for 3 successive days
Frequent causes of failure to respond Problems with the treatment facility

lactose.
Frequency : 3 hourly or 4 hourly. Amount : Starting with 130 ml / kg / d (16 ml/ kg/ feed), increased by

10 ml each feed until infant refuses to finish the feed. Caloric intake : 150 - 220 Kcal/kg/d. If < 130 Kcal /kg/d, the child is failing to respond Rehabilitation usually takes 2 - 6 weeks until 90% of the expected weight for height is attained (- 1 SD), When this occurs appetite diminishes.
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Poor environment for malnourished children Insufficient or inadequately trained staff Inaccurate weighing machines Food prepared or given incorrectly Insufficient food given Vitamin or mineral deficiency

Problems of individual children

Malabsorption of nutrients Rumination Infections, especially diarrhoea, dysentery, otitis media, pneumonia, tuberculosis, urinary tract infection, malaria, intestinal helminthiasis & HIV/AIDS

especially those who receive no oral supplementation & those who have darkly pigmented skin, which blocks penetration of ultraviolet light.
Pathophysiology

WHO guidelines

10 steps for routine management of children with severe malnutrition Prevent & treat - 1) Hypoglycaemia 2) Hypothermia 3) Dehydration 4) Electrolyte imbalance 5) Infection 6) Micronutrient deficiencies Provide special feeds for - 7) Initial stabilization 8) Catch - up growth Other - 9) Provide loving care & stimulation 10) Prepare for follow - up after discharge

22
Rickets

Rickets is a disease of growing bone that is unique to children. It is caused by failure of osteoid to calcify in growing children. Failure of osteoid to calcify in adults is called osteomalacia. Vitamin D deficiency rickets occurs when the metabolites of vitamin D are deficient. Less commonly, a dietary deficiency of calcium or phosphorus may also produce rickets. Vitamin D - 3 (cholecalciferol) is formed in the skin from a derivative of cholesterol under the stimulus of ultraviolet - B light. Rickets is observed only in growing children, although the effects may be observed later in life. Therefore, infants who are breastfed are at risk for rickets,
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Cholecalciferol (i.e. vitamin D - 3) is formed in the skin from 5 - dihydrotachysterol. This steroid undergoes hydroxylation in 2 steps. The first hydroxylation occurs at position 25 in the liver, producing calcidiol (25 - hydroxycholecalciferol), which circulates in the plasma as the most abundant of the vitamin D metabolites & is thought to be a good indicator of overall vitamin D status. The second hydroxylation step occurs in the kidney at the 1 position, where it undergoes hydroxylation to the active metabolite calcitriol (1, 25 - dihydroxycholecalciferol). This cholecalciferol is not technically a vitamin but a hormone. Calcitriol acts at 3 known sites to tightly regulate calcium metabolism. Calcitriol promotes absorption of calcium & phosphorus from the intestine, increases reabsorption of phosphate in the kidney & acts on bone to release calcium & phosphate. Calcitriol may also directly facilitate calcification. These actions increase the concentrations of calcium & phosphorus in extracellular fluid. The increase of calcium & phosphorus in extracellular fluid, in turn, leads to the calcification of osteoid, primarily at the metaphyseal growing ends of bones but also throughout all osteoid in the skeleton. Parathyroid hormone facilitates the 1 - hydroxylation step in vitamin D metabolism. In the vitamin D deficiency state, hypocalcemia develops, which stimulates excess parathyroid hormone, which stimulates renal phosphorus loss, further reducing deposition of calcium in the bone. Excess parathyroid hormone also produces changes in the bone similar to those occurring in hyperparathyroidism. Early in the course of rickets, the calcium concentration in the serum decreases. After the parathyroid response, the calcium concentration usually returns to the reference range, though phosphorus levels remain low. Alkaline

phosphatase, which is produced by overactive osteoblast cells, leaks to the extracellular fluids so that its concentration rises to anywhere from moderate elevation to very high levels. Intestinal malabsorption of fat & diseases of the liver or kidney may produce the clinical & secondary biochemical picture of nutritional rickets. Anticonvulsant drugs (e.g. phenobarbital, phenytoin) accelerate metabolism of calcidiol, which may lead to insufficiency & rickets, particularly in children who are kept indoors in institutions. Calcium & vitamin D intakes are low in infants who are fed vegan diets, particularly lacto vegans & monitoring of their vitamin D status is essential.
Mortality / Morbidity

along the costochondral junctions. The weakened ribs pulled by muscles also produce flaring over the diaphragm, which is known as Harrison groove. The sternum may be pulled into a pigeon - breast deformity. In more severe instances in children older than 2 years, vertebral softening leads to kyphoscoliosis. The ends of the long bones demonstrate that same knobby thickening. At the ankle, palpation of the tibial malleolus gives the impression of a double epiphysis (Marfan sign). Because the softened long bones may bend, they may fracture one side of the cortex (i.e. greenstick fracture).

Other problems to be considered

Skeletal deformity & short stature may occur. Severe rickets has been associated with respiratory failure in children & resulting pelvic distortion in females may lead to problems with vaginal delivery later in life.
History

The history in patients with rickets may include Generalized muscular hypotonia of an unknown mechanism is observed in most patients with clinical (as opposed to biochemical & radiographic) signs of rickets. Craniotabes manifests early in infants with vitamin D deficiency, although this feature may be normal in infants, especially for those born prematurely. If rickets occurs at a later age, thickening of the skull develops. This produces frontal bossing & delays the closure of the anterior fontanelle. In the long bones, laying down of uncalcified osteoid at the metaphases leads to spreading of those areas, producing knobby deformity, which is visualized on radiography as cupping & flaring of the metaphyses. Weight bearing produces deformities such as bowlegs & knock - knees. In the chest, knobby deformities results in the rachitic rosary
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The following should also be considered in patients with suspected rickets : Rare metabolic bone diseases, including hypophosphatasia have been confused with rickets in infancy. Jansen syndrome is a rare autosomal dominant form of short limbed dwarfism in which infants present with metaphyseal chondroplasia. Severe calcium deficiency can also cause a syndrome that is confused with vitamin D deficiency rickets. In premature infants, severe phosphorus deficiency that occurs when human milk is used without mineral fortification presents with rickets. Hereditary disorders of vitamin D metabolism have also been described, such as hypophosphatemic vitamin Dresistant rickets.
Laboratory Studies

The following findings may be noted in patients with rickets Early on in the course of rickets, the calcium (ionized fraction) is low; however it is often within the reference range at the time of diagnosis as parathyroid hormone levels increase. Calcidiol (25 - hydroxy vitamin D) levels are low & parathyroid hormone levels are elevated; however, determining calcidiol

& parathyroid hormone levels is typically not necessary. Calcitriol levels maybe normal or elevated because of increased parathyroid activity. The phosphorus level is invariably low for age unless recent partial treatment or recent exposure to sunlight has occurred. Alkaline phosphatase levels are elevated. A generalized aminoaciduria occurs from the parathyroid activity; aminoaciduria does not occur in familial hypophosphatemia rickets (FHR). Radiography is indicated in patients with rickets. The best single radiographic view for infants & children younger than 3 years is an anterior view of the knee that reveals the metaphyseal end & epiphysis of the femur & tibia. This site is best because growth is most rapid in this location, thus the changes are accentuated. The metaphyses exhibit widening & cupping because of their exaggerated normal concavity & irregular calcification. Because calcified osteoid is abundant, the provisional calcification zone of the metaphysis is much more distant from the calcification center of the epiphysis than is normal for age. Along the shaft, the uncalcified osteoid causes the periosteum to appear separated from the diaphysis. Generalized osteomalacia occurs (observed as osteopenia), with visible coarsening of trabeculae in contrast to the ground - glass osteopenia of scurvy. Examples of radiographic findings are shown in the images below.

Radiographs of the knee of a 3.6 - year - old girl with hypophosphatemia depict severe fraying of the metaphysis. Radiograph in a 4 - year - old girl with rickets depicts bowing of the legs caused by loading. Other Tests

Imaging Studies

Serum measurements include calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 25 - hydroxy vitamin D & 1, 25 dihydroxyvitamin D.
Treatment

Anteroposterior & lateral radiographs of the wrist of an 8 - year - old boy with rickets demonstrates cupping & fraying of the metaphyseal region.

Treatment for rickets may be gradually administered over several months or in a single - day dose of 15, 000 mcg (600, 000 U) of vitamin D. If the gradual method is chosen, 125 - 250 mcg (5000 - 10, 000 U) is given daily for 2 - 3 months until healing is well established & the alkaline phosphatase concentration is approaching the reference range. Because this method requires daily treatment, success depends on compliance. If the vitamin D dose is administered in a single day, it is usually divided into 4 or 6 oral doses. An intramuscular injection is also available. Vitamin D is well stored in the body & is gradually released over many weeks. Because both calcitriol & calcidiol have short half - lives, they are unsuitable; they would bypass the natural physiologic controls of vitamin D synthesis. The single - day therapy avoids problems with compliance & may be helpful in differentiating nutritional rickets from familial hypophosphatemia rickets (FHR). In nutritional rickets, the phosphorous level rises in 96 hours & radiographic healing is visible in 6 - 7 days. Neither happens with FHR. If severe deformities have occurred, orthopedic correction may be required after healing. Most of the deformities correct with growth.
Medical Care

Human milk contains little vitamin D & contains too little

80

phosphorus for babies who weigh less than 1500 g. Infants weighing less than 1500 g need special supplementation (i.e. vitamin D, calcium, phosphorus) if breast milk is their primary dietary source. Recommending a vitamin D supplement from the first week of life for susceptible infants who are breastfed is safe & effective and, therefore, should be considered.
Vitamin D

infection. Person - to - person contact is the most common means of transmission & is generally limited to close contacts. The period of greatest shedding of the hepatitis A virus is during the anicteric prodrome (14 - 21 d) of infection & corresponds to the time when transmission is highest.

Hepatitis A - Time course of infection

Fat - soluble vitamin used to treat vitamin D deficiency or for prophylaxis of deficiency.
Cholecalciferol

The incubation period usually lasts 2 - 6 weeks & the time to onset of symptoms may be dose related. The presence of disease manifestations & the severity of symptoms following hepatitis A virus infection directly correlate with patient age.
Mortality / Morbidity

Vitamin D - 3.1 mg provides 40000IU vitamin D activity.

Single - day dose method

15, 000 mcg (600, 000 U) PO qd divided in 4 - 6 doses for 1 d

Gradual method

125 - 250 mcg (5000 - 10, 000 U) qid for 2 - 3 mt.

23
Hepatitis A

Globally, hepatitis A virus infection is often asymptomatic & subclinical. The single most important determinant of illness severity is age; a direct correlation between increasing age & likelihood of adverse events (i.e. morbidity & mortality) is present. Other populations with increased likelihood of adverse sequelae caused by acute hepatitis A virus infection are those with significant comorbidities or concurrent chronic liver disease.
History

One of the more common causes of acute hepatitis is hepatitis A virus (HAV). The hepatitis A virus was isolated by Purcell in 1973. Humans appear to be the only reservoir for the hepatitis A virus.
Pathophysiology

The hepatitis A virus is a single - stranded, positive - sense, linear RNA enterovirus & a member of the Picornaviridae family. In humans, viral replication depends on hepatocyte uptake & synthesis & assembly occurs exclusively in liver cells. Acquisition results almost exclusively from ingestion (i.e. fecal - oral transmission). The hepatitis A virus can remain viable for many years. Boiling water is an effective means of destroying it & chlorine & iodine are similarly effective. Minimal cellular morphologic changes result from hepatocyte
81

o o o
o o

Not every patient with fever, hepatomegaly & jaundice has hepatitis A virus infection. Some of the important differential diagnoses for acute hepatitis warrant early & specific management. Prodrome Patients may have mild flulike symptoms of anorexia, nausea & vomiting, fatigue, malaise, myalgia & mild headache. Icteric phase Dark urine appears first (bilirubinuria). Jaundice is less likely in children & is uncommon in infants. The degree of icterus also increases with age. Abdominal pain occurs in approximately 40% of patients. Itching (pruritus), although less common than jaundice, is

generally accompanied by jaundice. Arthralgia & skin rash, although associated, are less frequent than the above symptoms. Rash more often occurs on the lower limbs. Hepatomegaly is common. Jaundice or scleral icterus may occur. Patients may have a fever with temperatures of up to 40C.

Physical

Causes

Most patients have no defined risk factors for hepatitis A. Risk factors for acquisition of hepatitis A include the following Personal contacts Institutionalization Occupation (e.g. daycare) Foreign travel Male homosexuality Illicit parenteral drug use
Differential diagnosis

Budd - Chiari Syndrome Cytomegalovirus Other Viral Hepatitis Acute drug - induced liver injury Acute HIV infection Drug - induced hypersensitivity reactions
Laboratory Studies

o
o

Liver enzymes Rise of levels in ALT & Aspartate aminotransferase (AST) assays are sensitive for this disease. Levels may exceed values of 10, 000 mIU/mL, with ALT levels generally greater than AST levels. Levels usually return to reference ranges over 5 20 weeks. Rises in alkaline phosphatase accompany the acute disease & may progress during the cholestatic phase of the illness following the rises in transaminase levels. Hepatic synthetic function Bilirubin level rises soon after the onset of bilirubinuria & follows rises in ALT & AST levels. Levels may be high & can remain elevated for several months; persistence beyond 3 months indicates cholestatic hepatitis A virus infection. Both direct & indirect fractions increase because of hemolysis, which often occurs in acute hepatitis A virus infection. Slight fall in serum albumin level may accompany the illness. Prothrombin time Prothrombin time usually remains within or near the reference range In the presence of encephalopathy, an elevated prothrombin time has ominous implications (e.g. fulminant hepatic failure). CBC count Mild lymphocytosis is not uncommon. Pure red cell aplasia & pancytopenia may rarely accompany infection.

The diagnosis of acute hepatitis A virus infection is based on serologic testing for IgM antibody to the hepatitis A virus. Test results for anti - hepatitis A virus IgM are positive at the time of onset of symptoms & usually accompany the first rise in Alanine aminotransferase (ALT) level. This test is sensitive & specific. IgM persists in patients with relapsing hepatitis for the duration of this pattern of disease.
82

Imaging Studies

An ultrasound scan may be required when alternative diagnoses warrant exclusion & should assess vessel patency & evaluate any evidence supporting unsuspected underlying chronic liver disease.
Medical Care

For acute cases of hepatitis A virus infection, therapy is generally supportive, with no specific treatment. Initial therapy often consists of bed rest. Nausea & vomiting are treated with antiemetic.

Dehydration may require hospital admission & intravenous fluids. In most instances, hospitalization is unnecessary. Most children have minimal symptoms.

Activity

Bed rest during the acute illness may be important, although data to support this practice are lacking. Restricting transmission is important, especially in the early phases of the illness. The goals of pharmacotherapy are to reduce morbidity & to prevent complications.

24 25
Pertussis

respiratory epithelium. Bacteria spread via aerosolized droplets from coughing of infected individuals. Humans are the sole reservoir for the organisms. Transmission can occur through direct face - to - face contact, sharing a confined space, or through contact with oral, nasal, or respiratory secretions from an infected source. Pertussis is highly contagious, with as many as 80% of susceptible household contacts becoming infected after exposure. Young infants, especially those born prematurely & patients with underlying cardiac, pulmonary, neuromuscular, or neurologic disease are at high risk for contracting the disease & for complications Infants born prematurely & patients with underlying cardiac, pulmonary, neuromuscular, or neurologic disease are at high risk for complications of pertussis (e.g. pneumonia, seizures, encephalopathy & death). Older children, adolescents & adults often have mild or atypical illness. Approximately one half of adolescents with pertussis cough for 10 weeks or longer. Compared with older children & adults, infants younger than 6 months with pertussis are more likely to have severe disease, to develop complications & to require hospitalization. Typically, the incubation period of pertussis ranges from 3 - 12 days. Pertussis is a 6 - week disease divided into catarrhal, paroxysmal & convalescent stages, each lasting from 1 - 2 weeks.

Mortality / Morbidity

Pertussis, commonly known as whooping cough or cough of 100 days, is a respiratory tract infection characterized by a paroxysmal cough. It was first identified in the 16th century. In 1906, Bordet isolated the most common causative organism, Bordetella pertussis. Bordetella parapertussis has also been associated with whooping cough in humans. Before the advent of vaccinations, pertussis was a major cause of morbidity & mortality among infants & children. Reported cases of pertussis decreased by more than 99% after the introduction of pertussis vaccine combined with diphtheria & tetanus toxoids in the 1940s. Humans are the sole reservoir for B pertussis & B parapertussis. B pertussis is a gram - negative pleomorphic bacillus that spreads via aerosolized droplets from coughing of infected individuals. B pertussis attaches to & damages ciliated
83

History

Pathophysiology

The 3 stages of disease progression are as follows : Stage 1 : The initial (catarrhal) phase is indistinguishable from

common upper respiratory infections with nasal congestion,

rhinorrhea & sneezing, variably accompanied by low - grade fever, tearing & conjunctival congestion. Pertussis is most infectious when patients are in the catarrhal phase, but pertussis may remain communicable for 3 or more weeks after the onset of cough. Stage 2 : Patients in the second (paroxysmal) phase present with paroxysms of intense coughing lasting up to several minutes. In older infants & toddlers, the paroxysms of coughing occasionally are followed by a loud whoop as inspired air goes through a still partially closed airway. Infants younger than 6 months do not have the characteristic whoop but may have apneic episodes & are at risk for exhaustion. Cough bout followed by vomiting episode & flushing of face are common in affected children. Stage 3 : Patients in the third (convalescent) stage have a chronic cough, which may last for weeks.

Physical

In patients with uncomplicated pertussis, physical examination findings contribute little to the diagnosis. In all patients with pertussis, fever is typically absent. Most patients do not have signs of lower respiratory tract disease. Conjunctival hemorrhages & facial petechiae are common & result from intense coughing.
Causes

Therefore, clinicians need to make the diagnosis of pertussis presumptively in patients with a history of intense paroxysmal coughing with or without whooping, color changes, posttussive vomiting, incomplete or absent pertussis vaccination & finding of lymphocytosis on laboratory examination. A clinical case of pertussis is defined as one of the following : o An acute coughing illness that lasts at least 14 days with at least one characteristic pertussis symptom (i.e. paroxysmal cough, posttussive vomiting, or inspiratory whoop) o A cough that lasts at least 14 days in an outbreak setting A confirmed case is defined as one of the following : o Any cough illness in which B pertussis is isolated & cultured o A case consistent with the clinical case definition confirmed by polymerase chain reaction (PCR) findings or epidemiologic linkage to a laboratory - confirmed case Leukocytosis (15, 000 - 50, 000 10 3/L) with absolute lymphocytosis occurs during the late catarrhal & paroxysmal phases. It is a nonspecific finding but correlates with severity of the disease.
Imaging Studies

B pertussis & B parapertussis are the causative organisms for pertussis infection in humans.
Differential diagnosis

Chest radiography may reveal perihilar infiltrates or edema with variable degrees of atelectasis. Consolidation is indicative of secondary bacterial infection or, rarely, pertussis pneumonia. Occasionally, pneumothorax, pneumomediastinum, or air in the soft tissues may be seen.
Medical Care

Afebrile Pneumonia Syndrome Bronchiolitis Chlamydial Infections Mycoplasma Infections Respiratory Syncytial Virus Infection
Laboratory Studies

Laboratory confirmation of pertussis is difficult & delayed.

84

The mainstay of therapy in patients with active pertussis infections is supportive. The goals of therapy include limiting the number of paroxysms, observing the severity of cough, providing assistance when necessary & maximizing nutrition, rest & recovery. For patients aged 1 month or older, macrolide antibiotics such as erythromycin, clarithromycin & azithromycin, are the preferred agents. Erythromycin & clarithromycin are not recommended in infants younger than 1 month because their

use has been associated with increased risk for infantile hypertrophic pyloric stenosis (IHPS). Azithromycin is the recommended agent in the youngest patients. Hospitalization should be strongly considered for patients at risk of severe disease & complications, including infants younger than 3 months; infants aged 3 - 6 months, unless observed paroxysms are not severe; premature young infants; & infants or children with underlying pulmonary, cardiac, or neuromuscular disease. o Monitor heart rate, respiratory rate & oxygen saturation of hospitalized patients continuously, especially in relation to coughing paroxysms. Coughing, feeding, vomiting & weight changes should be recorded. o Pay attention to the young infants hydration & nutritional status. o Patients who are severely ill may require treatment in an ICU. o Antimicrobial agents given during the catarrhal phase may ameliorate the disease. Once cough is established, antimicrobial agents may not alter the course of the illness but are still recommended to limit the spread of disease. The use of corticosteroids, albuterol & other beta2 - adrenergic agents for the treatment of pertussis is not advised.
Antibiotics

Azithromycin is typically administered in doses of 10 - 12 mg/ kg/d PO in 1 dose for a total of 5 days. Clarithromycin is administered at 15 - 20 mg/kg/d PO in 2 divided doses, not to exceed 1 g/d for 5 - 7 days. Trimethoprim - sulfamethoxazole is another antibiotic option, with the following dosage : trimethoprim 8 mg/kg/d & sulfamethoxazole 40 mg/kg/d in 2 divided doses.

26
Poliomyelitis
85

Poliomyelitis first occurred nearly 6000 years ago in the time of the ancient Egyptians. The evidence for this is in the withered & deformed limbs of certain Egyptian mummies. Following is a timeline of the recorded history of this disease : 1789 : First known description of poliomyelitis by Underwood. 1834 : First epidemic of poliomyelitis on the island of St. Helena. 1855 : First description by Duchenne of the pathologic process in poliomyelitis involving the anterior horn cells of the spinal cord. 1908 : Transmission of poliomyelitis to a monkey by Landsteiner. 1909 : Passage of the virus through a monkey by Flexner. 1949 : Growth of the virus on tissue culture. 1951 : Three types of polio virus isolated & identified. 1954 : First large - scale trial of Salk (dead vaccine) by injection. 1958 : First general use of Sabin (live attenuated vaccine) by mouth. Poliomyelitis is an enteroviral infection that can manifest in 4 different forms : inapparent infection, abortive disease, nonparalytic poliomyelitis & paralytic disease. Polioviruses are RNA enteroviruses within the Picornaviridae family. These viruses are resistant to ether & chloroform but can be inactivated by formaldehyde. They multiply in the GI tract but are particularly neurotropic. Poliovirus is transmitted through the oral - fecal route or by ingestion of contaminated water. Before the 19th century, poliomyelitis occurred sporadically. During the 19th & 20th centuries, epidemic poliomyelitis was more frequently observed, reaching its peak in the mid 1950s. The worldwide prevalence of this infection has decreased significantly since then because of aggressive immunization programs.

The typical contractures of post polio residual paralysis

Pathophysiology

The poliovirus is shed in oral secretions for several weeks & in the feces for several months. Three antigenically distinct strains are known, with type I accounting for 85% of cases of paralytic illnesses. Infection with one type does not protect from the other types; however, immunity to each of the 3 strains is lifelong. The incubation period for poliovirus is 5 - 35 days. The viral particles initially replicate in the nasopharynx & GI tract & then invade lymphoid tissues, with subsequent hematologic spread. After a period of viremia, the virus becomes neurotropic & produces destruction of the motor neurons in the anterior horn
cells in the spinal cord & brainstem.

When nonparalytic poliomyelitis develops, symptoms are usually those observed in abortive disease in addition to meningeal irritation. Paralytic poliomyelitis involves systemic manifestation, such as respiratory failure, in addition to symptoms observed in nonparalytic poliomyelitis. Patients who have recovered from poliomyelitis occasionally develop a post poliomyelitis syndrome, in which recurrences of weakness or fatigue are observed & which usually involve groups of muscles that were initially affected. This post polio syndrome may develop 20 - 40 years after infection with poliovirus.

Physical

The destruction of motor neurons leads to the development of flaccid paralysis, which may be bulbar or spinal in distribution.

Mortality / Morbidity

Mortality is more frequently observed in cases of paralytic poliomyelitis & is associated with complications such as respiratory failure. Although most cases of poliomyelitis (90 - 95%) are inapparent, 5 - 10% of patients who acquire this infection develop symptoms.
Age

Poliomyelitis is mainly the disease of children. However, individuals of any age (especially those who are immunocompromised) may also develop the disease.
History

Most patients infected with poliovirus develop inapparent infections & are frequently asymptomatic. In cases of abortive poliomyelitis (5 - 10%), a history of the following is found with normal neurologic examination findings o Anorexia o Vomiting o Abdominal pain o Duration of illness usually less than 5 days
86

The spectrum of disease varies from inapparent infection to paralytic disease. In mild cases, the following nonspecific signs & symptoms are observed & usually resolve within a few days : o Fever o Headache o Nausea o Vomiting o Abdominal pain o Oropharyngeal hyperemia Nonparalytic poliomyelitis is characterized by the symptoms described above in addition to the following : o Nuchal rigidity o More severe headache o Back & lower extremity pain o Meningitis with lymphocytic pleocytosis Paralytic poliomyelitis occurs in fewer than 5% of affected patients & is characterized by the following : o Compromise of the motor neurons may be localized or widespread.

o o o

More frequently, asymmetric loss of muscle function is observed with involvement of major muscle groups. Muscle atrophy is generally observed several weeks after the beginning of symptoms. Recovery may be complete, partial, or absent.

shallow & irregular. Bulbar polio is not always associated with spinal muscles paralysis.
Clinical findings

Acute stage

Poliovirus is primarily spread by fecalhandoral transmission from one host to another. The virus is shed in oral secretions for several weeks & in the feces for several months. Poliovirus infections can be divided into minor & major forms.
Minor illnesses

The minor associated illnesses occur 13 days before the onset of paralysis, with gastrointestinal complaints such as nausea & vomiting, abdominal cramps & pain & diarrhea. There are also systemic manifestations, such as sore throat, fever, malaise & headache. This stage lasts usually for 23 weeks but may extend for up to 2 months; the presence of any tenderness in the muscles is evidence that the acute stage is not over.
Major illnesses

The clinical findings associated with an attack of polio are as follows : Fever, neck stiffness (nuchal rigidity) & a pleocytosis in the CSF Profound asymmetrical muscle weakness The initial phase is typically followed by some recovery of muscle strength, but permanent weakness results from necrosis of anterior horn cells Rarely, a transverse myelitis with paraparesis, urinary retention, sensory symptoms & signs, autonomic dysfunction (including hyperhidrosis or hypohidrosis) & decreased limb temperature may occur due to involvement of vasomotor centre.
Signs in poliomyelitis

The major associated illnesses include all forms of central nervous system (CNS) disease caused by poliovirus, including aseptic meningitis (or nonparalytic polio), polio encephalitis, bulbar polio & paralytic poliomyelitis, alone or in combination.
Spinal form

In this form paralysis of the spinal muscles occurs suddenly. Myalgia, hyperasthesis, tremors & diminished deep tendon reflexes follow the flaccid paralysis. Respiratory insufficiency may occur due to paralysis of the diaphragm & intercoastal muscles.
Bulbar form

Neck rigidity Tripod sign when the child is asked to sit without any support, he moves from side to side, flexes the knees & puts his hands behind him for sitting. Kiss the knee test In sitting position the child is asked to kiss his knees. He cannot do so due to stiffness of the spine & may suddenly draw up his knees. Head drop sign when the examiners hand is placed under the shoulders of the child & the trunk is raised, the head lags behind. Infections with polioviruses can be predisposed by factors such as exercise, fatigue & tonsillectomy. Additionally, patients who are immunocompromised, such as those with human immunodeficiency virus (HIV) infection, B - cell dysfunction, immunoglobulin A (IgA) deficiency, or severe combined immunodeficiency, are particularly at high risk of developing poliomyelitis when exposed to both wild -

Causes

In this type the paralysis of the vagus nerve causes weakness of the soft palate, pharynx & vocal cords. When respiratory centre is involved respiration becomes
87

type polioviruses & vaccine - attenuated viruses present in the oral poliovirus vaccine.
Differential Diagnoses

o
o

Botulism Enteroviral Infections Guillain - Barre Syndrome (infective polyneuritis) Spinal Muscular Atrophy Myotonic dystrophy
Laboratory Studies

Rabies Tetanus Aseptic meningitis Severe hypokalemia Transverse myelitis

Tracheostomy care is often needed in patients who require long - term ventilatory support. Physical therapy is indicated in cases of paralytic disease. In paralytic disease, provide frequent mobilization to avoid development of chronic decubitus ulcerations. Active & passive motion exercises are indicated during the convalescent stage. Fecal impaction is frequent in cases of paralytic disease & can be treated with laxatives as soon as it develops.

Surgical Care

Obtain specimens from the cerebrospinal fluid (CSF), stool & throat for viral cultures in patients with suspected poliomyelitis infection to differentiate with septic meningitis. A 4 - fold increase in the immunoglobulin G (IgG) antibody titers or a positive anti - immunoglobulin M (IgM) titer during the acute stage is diagnostic.

Total hip arthroplasty is a surgical therapeutic option for patients with paralytic sequelae of poliomyelitis who develop of hip dysplasia & degenerative disease.
Recovery stage

Diet

Because patients with poliomyelitis are prone to develop constipation, a diet rich in fiber is usually indicated.
Treatment

In this stage, also known as the convalescent stage, the acute symptoms & muscle tenderness disappear & the paralyzed muscles begin to recover. This stage lasts for up to 2 years after the onset of the disease. During this entire period, there is gradual recovery of the muscles; the recovery is rapid in the first 6 months but is slower during the subsequent months.
Residual - paralysis stage

No antiviral agents are effective against poliovirus. General supportive treatment for the pyrexia & irritation, for the prevention of secondary respiratory infection, and for any respiratory paralysis are the main aspects of treatment. The paralyzed legs are supported by plaster splints or pillows & sandbags to keep the hip joints in 5 of flexion & in neutral rotation. The knee joint is held at 5 of flexion & the foot is supported in a 90 position. Splinting relieves pain & spasm & prevents the development of deformities. The treatment of poliomyelitis is mainly supportive. Analgesia is indicated in cases of myalgias or headache. Mechanical ventilation is often needed in patients with bulbar paralysis.
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The period beyond 2 years after the onset of the disease is called the residual - paralysis stage. No recovery of muscle power occurs in this stage. Deformities are liable to occur due to imbalance of muscle power & poor posture. There is also disuse atrophy of muscles & shortening of the leg due to interference with growth. In neglected cases, gross fixed deformities of the hip, knee & foot occur with severe wasting of muscles. Children with extensive paralysis & gross deformities have to crawl on all fours to move from place to place.
Post - polio syndrome

Post - polio syndrome is the term used for the newly occurring late manifestations of poliomyelitis that develop in patients 30 to 40 years after the occurrence of the acute illness. It has been estimated that 2560% of the patients who had acute polio may experience

these late effects of the disease.

Medical Therapy

o o o

Release of joint contractures Reestablish muscle balance around the joint to prevent deformities Muscle transplantation to replace a paralyzed muscle Stabilization of relaxed or flail joint by the following : Tenodesis Fixation of ligaments Construction of artificial check ligaments Arthrodesis Limb lengthening Ilizarov techniques Joint replacement surgery

Arthrodesis is used to correct a deformity, relieve pain in arthritic joints & reduce the number of joints a weak muscle is acting across. Limb lengthening Often, poliomyelitis is unilateral, causing limb - length inequality, which occasionally requires limb lengthening.
Joint replacement surgery

In patients with post - polio residual deformities, joint replacement can be indicated. Recurrence of instability & progressive functional deterioration are possible in all knees affected by poliomyelitis that have undergone total knee replacement, but they appear to occur more commonly in more severely affected knees.
Ilizarov techniques

Efficient physiotherapy

Efficient physiotherapy is the mainstay of the management of poliomyelitis; exercise therapy, hydrotherapy & electrical stimulation of muscles are essential in the management of paralytic polio.
Management of post - polio syndrome

There are many drawbacks to using conventional approaches for the treatment of complex foot deformities, such as the increased risk of neurovascular injury, soft tissue injury & shortening of the foot. An alternative approach that can eliminate these problems is the Ilizarov method. Pin - tract problems, contractures, residual deformity & recurrence of deformity can complicate the Ilizarov method.

Many patients require revision of orthotic devices such as braces, canes & crutches or may use new, lighter orthotic devices to treat new symptoms. Common issues include genu recurvatum, knee pain, back pain, degenerative arthritis, or arthralgia. Surgery for scoliosis or fractures may also be necessary to treat new conditions.
Treatment of residual paralysis

(27)
Rubella

The final aim should be for patients to return home & be accepted & integrated into their communities. Since overuse weakness is frequently present in these patients, the role of slowly progressive, non fatiguing exercise in their rehabilitation is emphasized. Generalized fatigue may be treated with energy conservation, weight - loss programs & lower - extremity orthoses. Arthrodesis (surgical immobilization of a joint by fusion of the bones)
89

The name rubella is derived from a Latin term meaning little red. Rubella is generally a benign, communicable exanthematous disease. It is caused by rubella virus, which is a member of the Rubivirus genus of the family Togaviridae. Rubella & congenital rubella syndrome are caused by rubella virus. Only one antigenic type of rubella virus is available & humans are the only natural hosts. Clinical manifestations & severity of illness vary with age. For instance, infection in younger children is characterized by mild

constitutional symptoms, rash & suboccipital adenopathy; conversely, in older children, adolescents & adults, rubella may be complicated by arthralgia, arthritis & thrombocytopenic purpura. The major complication of rubella is its teratogenic effects on fetus when pregnant women contract the disease, especially in the early weeks of gestation. The virus can be transmitted to the fetus through the placenta & is capable of causing serious congenital defects, abortions & stillbirths.

chromosomal breakage or due to production of a protein that inhibits mitosis. Regardless of the mechanism, any injury affecting the fetus in the first trimester (during the phase of organogenesis) results in congenital organ defects.
Mortality / Morbidity

In contrast to postnatal rubella, which is not a debilitating disease, congenital rubella infection may result in growth delay, learning disability, mental retardation, hearing loss, congenital heart disease & eye, endocrinologic & neurologic abnormalities.
History

Pathophysiology Postnatal rubella

The usual portal of entry of rubella virus is the respiratory epithelium of the nasopharynx. The virus is transmitted via the aerosolized particles from the respiratory tract secretions of infected individuals. The virus attaches to & invades the respiratory epithelium. It then spreads hematogenously (primary viremia) to regional & distant lymphatics & replicates in the reticuloendothelial system. This is followed by a secondary viremia that occurs 6 - 20 days after infection. During this viremic phase, rubella virus can be recovered from different body sites including lymph nodes, urine, cerebrospinal fluid (CSF), conjunctival sac, breast milk, synovial fluid & lungs. Viremia peaks just before the onset of rash & disappears shortly thereafter. An infected individual begins to shed the virus from the nasopharynx 3 - 8 days after exposure for 6 - 14 days after onset of the rash.
Congenital rubella syndrome

o o o
90

Fetal infection occurs transplacentally during the maternal viremic phase, but the mechanisms by which rubella virus causes fetal damage are poorly understood. The fetal defects observed in congenital rubella syndrome are likely secondary to vasculitis resulting in tissue necrosis without inflammation. Another possible mechanism is direct viral damage of infected cells. It is demonstrated that cells infected with rubella in the early fetal period have reduced mitotic activity. This may be the result of

Postnatal rubella Exposure : Rubella virus is transmitted from person to person via the aerosolized particles from the respiratory tract. A history of exposure may not be present. Children may acquire the infection from a completely asymptomatic patient or from an individual shedding the virus during the incubation period. Incubation period : The incubation is usually 14 - 21 days after exposure to a person with rubella. Prodromal phase : Prodromal symptoms are unusual in young children. The following signs & symptoms usually appear 1 - 5 days before the onset of rash : Eye pain on lateral & upward eye movement (a particularly troublesome complaint) Conjunctivitis Sore throat Headache General body aches Low - grade fever Chills Anorexia Nausea Tender lymphadenopathy (particularly posterior auricular & suboccipital lymph nodes)

Forchheimer sign (an enanthem, consists of pinpoint or larger

o o o

petechiae that usually occur on the soft palate) Congenital rubella history focuses on the following : The number of weeks of pregnancy when maternal exposure to rubella occurred (The risk of congenital rubella syndrome is higher if maternal exposure occurs during the first trimester.) Maternal history of immunization or medical history of rubella Evidence of intrauterine growth retardation during pregnancy Manifestations suggestive of congenital rubella syndrome in a child

Physical Postnatal rubella

Rash The exanthem of rubella consists of a discrete rose - pink maculopapular rash ranging from 1 - 4 mm.

Image in a 4 - year - old girl with a 4 - day history of low - grade fever, symptoms of an upper respiratory tract infection & rash.

o o o

The synonym 3 - day measles derives from the typical course of rubella exanthem that starts initially on the face & neck & spreads centrifugally to the trunk & extremities within 24 hours. It then begins to fade on the face on the second day & disappears throughout the body by the end of the third day. Temperature : Fever is usually not higher than 38.5C (101.5F). Lymph nodes : Enlarged posterior auricular & suboccipital lymph nodes are usually found on physical examination. Mouth : The Forchheimer sign may still be present on the soft palate. Congenital rubella syndrome The classic triad presentation of congenital rubella syndrome consists of the following : Sensorineural hearing loss is the most common manifestation
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of congenital rubella syndrome. Hearing impairment may be bilateral or unilateral & may not be apparent until the second year of life. Ocular abnormalities including cataract, infantile glaucoma& retinopathy. Rubella retinopathy consists of a salt - & - pepper pigmentary change or a mottled, blotchy, irregular pigmentation, usually with the greatest density in the macula. Congenital heart disease including patent ductus arteriosus (PDA) & pulmonary artery. Other findings in congenital rubella syndrome include the following : Intrauterine growth retardation, prematurity, stillbirth & abortion CNS abnormalities, including mental retardation, behavioral disorders, encephalographic abnormalities, hypotonia, meningoencephalitis & microcephaly Hepatosplenomegaly Jaundice Hepatitis Skin manifestations, including blueberry muffin spots that represent dermal erythropoiesis & dermatoglyphics abnormalities Bone lesions, such as radiographic lucencies Endocrine disorders, including late manifestations in congenital rubella syndrome usually occurring in the second or third decade of life (e.g. thyroid abnormalities, diabetes mellitus) Hematologic disorders, such as anemia & thrombocytopenic purpura Mycoplasma Infections Parvovirus B19 Infection Syphilis Toxoplasmosis

Differential Diagnoses

Contact Dermatitis Cytomegalovirus Infection Enteroviral Infections Herpesvirus 6 Infection Measles

Mononucleosis & Epstein - Barr Virus Infection

Laboratory Studies Postnatal rubella

passive transfer of maternal antibody (i.e. equivalent of a 2 fold decline in HI titer per mo) in a compatible clinical situation.
Imaging Studies

A clinical diagnosis of rubella may be difficult to make because many exanthematic diseases may mimic rubella infection. In addition, as many as 50% of rubella infections may be subclinical; therefore, laboratory studies are important to confirm the diagnosis of acute rubella infection. The laboratory diagnosis of rubella can be made either though serologic testing or by viral culture. The serologic diagnosis consists of demonstrating the presence of rubella - specific immunoglobulin M (IgM) antibody in a single serum sample or observation of a significant (> 4 - fold) rise in rubella specific immunoglobulin G (IgG) antibody titer between the acute & convalescent serum specimens drawn 2 - 3 weeks apart. Among all the serologic tests available, ELISA is the most widely used because it is relatively inexpensive, technically easy to perform, rapid & very sensitive. Congenital rubella in infants & children is diagnosed by viral isolation or by serologic testing. In contrast to postnatal infection, viral isolation is the preferred technique in congenital rubella syndrome because rubella serology may be difficult to interpret in view of transplacental passage of rubella - specific maternal IgG antibody. Congenital rubella syndrome can also be diagnosed using placental biopsy, rubella antigen detection by monoclonal antibody & polymerase chain reaction (PCR). Specimens used for viral isolation in congenital rubella include nasopharyngeal swab, urine, cerebrospinal fluid & buffy coat of the blood. Congenital rubella syndrome should be strongly suspected in infants older than 3 months if rubella - specific IgG antibody levels are observed & do not decline at the rate expected from
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o o

o o

Congenital rubella

Postnatal rubella : Imaging studies are usually not performed in postnatal rubella. Congenital rubella syndrome Chest radiography is indicated for infants who develop respiratory distress or other respiratory symptoms to exclude rubella - related interstitial pneumonitis or pulmonary edema that may result from congestive heart failure in children with severe or complicated congenital heart anomalies. Radiography of the long bones may reveal radiolucencies in the metaphyses of long bones. Echocardiography is important for patients with congenital heart defects to help diagnose the type of heart anomaly & evaluate the severity of the heart defect so that appropriate surgical plans can be made. CT scanning of the head may reveal intracranial calcifications & enlargement of the ventricles. MRI of the head may reveal cortical atrophy & white matter changes in patients with late - onset progressive panencephalitis. CBC count may reveal leukopenia & thrombocytopenia. It is used to monitor the course of thrombocytopenia. Liver function tests, such as total & direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase & gamma - glutamyl transpeptidase levels may reveal hepatic injury due to disseminated rubella infection, especially in neonates.

Other Tests

Procedures

Lumbar puncture is indicated to evaluate for possible causes in children who develop signs & symptoms of meningoencephalitis, such as bulging anterior fontanel, irritability, hypotonia, seizures, lethargy, head retraction & arching of the back.

Medical Care Postnatal rubella

o o

Treatment is supportive. No specific antiviral agent for rubella is currently available. Starch baths & antihistamines may be useful for adult patients with uncomplicated rubella & troublesome itching. For complicated cases, treatment is as follows : For severe arthritis affecting weight - bearing joints, encourage rest. Nonsteroidal anti - inflammatory drugs (NSAIDs) may be helpful, but corticosteroids are not indicated. For patients with encephalitis, provide supportive care with adequate fluid & electrolyte maintenance. Thrombocytopenia is usually self - limited but, if severe, consider intravenous immunoglobulin (IVIG). Corticosteroids have not demonstrated any specific benefit. Splenectomy is not indicated. Treatment is supportive. Provide vision screening & hearing screening for asymptomatic newborns. Treatment of symptomatic newborns is as follows : Provide careful evaluation of the eyes & ophthalmology referral for babies with corneal clouding, cataract & retinopathy. Corneal clouding may indicate infantile glaucoma. Babies with congenital rubella syndrome who develop respiratory distress may require supportive treatment in the ICU. Hepatosplenomegaly is monitored clinically. No intervention is required. Patients with hyperbilirubinemia may require phototherapy or exchange transfusions if jaundice is severe to prevent kernicterus. IVIG may be considered in infants who develop severe thrombocytopenia. Corticosteroids are not indicated. Infants who have a rubella - related heart abnormality should
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be carefully observed for signs of congestive heart failure. Echocardiography may be essential for diagnosis of heart defects. Contact isolation is required for patients with congenital rubella during hospitalizations because babies are infected at birth & are usually contagious until older than 1 year unless viral cultures have produced negative results. Postnatal rubella : Surgical care is not indicated. Congenital rubella syndrome Surgical treatment may be required for congenital heart anomalies, including patent ductus arteriosus (PDA), Coarctation of aorta, ventricular septal defect (VSD), atrial septal defect (ASD) & pulmonary artery stenosis. Surgical treatment may be required for eye defects such as glaucoma, cataract & retinal neovascularization.

Surgical Care

Congenital rubella syndrome

Activity

Activity in rubella can be maintained as tolerated; however, rest is advised for patients who develop arthralgia or arthritis.
Medication

Drug therapy is currently not a component of the standard of care for rubella.

28
Tetanus

o o o

o o

Tetanus is an intoxication characterized by increased muscle tone & spasms caused by the release of the neurotoxin tetanospasmin by Clostridium tetani following inoculation into a human host. Tetanus occurs in several clinical forms, including generalized, cephalic, localized & neonatal disease. Most cases of tetanus are caused by direct contamination of

Pathophysiology

wounds with clostridial spores. Wounds with low oxidation - reduction potential, such as those with dead or devitalized tissue, a foreign body, or active infection, are ideal for germination of the spores & release of toxin. Infection by C tetani results in a benign appearance at the portal of entry because of its inability to evoke an inflammatory reaction (unless co - infection with other organisms develops). Tetanospasmin, a zinc metalloprotease, is released in the wound & binds to the peripheral motor neuron terminal, enters the axon, and, via retrograde intra neuronal transport, reaches the nerve cell body in the brainstem & spinal cord. The toxin migrates across the synapse to presynaptic terminals where it blocks the release of the inhibitory neurotransmitters glycine & gamma - aminobutyric acid (GABA) by cleaving proteins crucial for the proper functioning of the synaptic vesicle release apparatus. One of these important proteins is synaptobrevin. This diminished inhibition results in an increase in the resting firing rate of the motor neuron, which is responsible for the observed muscle rigidity. Finally, tetanospasmin can block neurotransmitter release at the neuromuscular junction, causing weakness & paralysis. Localized tetanus develops when only the nerves supplying the affected muscle are involved. Generalized tetanus develops when the toxin released at the wound spreads through the lymphatics & blood to multiple nerve terminals. The blood - brain barrier prevents direct entry of toxin to the CNS.
Prevalence

Mortality / Morbidity

A rating scale for the severity & the prognosis of tetanus is described below.
Score one point for each of the following :

Incubation period less than 7 days Period of onset less than 48 hours Acquired from burns, surgical wounds, compound fractures, septic abortion, umbilical stump, or intramuscular injection Narcotic addiction Generalized tetanus Temperature greater than 104F (40C) Tachycardia greater than 120 beats per minute (> 150 beats per minute in neonates) Score of 0 - 1 indicates mild severity with less than a 10% mortality rate. Score of 2 - 3 indicates moderate severity with a 10 - 20% mortality rate. Score of 4 indicates severe tetanus with a 20 - 40% mortality rate. Score of 5 - 6 indicates very severe tetanus with greater than a 50% mortality rate. Cephalic tetanus is always severe or very severe. Neonatal tetanus is always very severe. The etiologic agent of tetanus, C tetani, is an anaerobic, motile, gram - positive rod that forms an oval, colorless, terminal spore & assumes a shape that resembles a tennis racket or a drumstick. The organism is found worldwide. The spores may survive for years in some environments & are resistant to disinfectants & to boiling for 20 minutes.

Total score indicates the severity & the prognosis as follows :

History

C tetani is found worldwide in soil, on inanimate objects, in animal feces, and, occasionally, in human feces. The disease is common in areas where soil is cultivated, in rural areas, in warm climates, during summer months & among males. In countries without a comprehensive immunization program, tetanus predominantly develops in neonates & young children.
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Generalized tetanus

Generalized tetanus is the most commonly found form of tetanus. The incubation period is 7 - 21 days, largely depending on

the distance of the injury site from the CNS. Trismus is the most common presenting symptom. Other early features include irritability, restlessness, diaphoresis & dysphagia with hydrophobia, drooling & spasm of the back muscles. These early manifestations reflect involvement of bulbar & paraspinal muscles, possibly because they are innervated by the shortest axons. The condition may progress for 2 weeks despite antitoxin therapy because of the time needed for intra - axonal antitoxin transport.
Localized tetanus

Localized tetanus involves an extremity with a contaminated wound & widely varies in severity. This is an unusual form of tetanus & the prognosis for survival is excellent.
Cephalic tetanus

profound diaphoresis, hyperthermia, rhabdomyolysis, laryngeal spasm & urinary retention Localized tetanus : In mild cases, patients may have weakness of the involved extremity, presumably due to partial immunity. In more severe cases, intense painful spasms occur & usually progress to generalized tetanus. Cephalic tetanus : Cranial nerve findings & rapid progression are typical. This form may remain localized or progress to generalized tetanus. Tetanus neonatorum : Physical examination findings are similar to generalized tetanus findings.

Causes

Cephalic tetanus generally follows head injury or develops with infection of the middle ear. Symptoms consist of isolated or combined dysfunction of the cranial motor nerves (most frequently the seventh cranial nerve). It may remain localized or progress to generalized tetanus. This is an unusual form of tetanus with an incubation period of 1 - 2 days. The prognosis for survival is usually poor.
Tetanus neonatorum

Causes of tetanus include under immunization & the use of contaminated materials in newborn care
Differential Diagnoses

This is generalized tetanus that results from infection of a neonate. The usual cause is the use of contaminated materials to sever or dress the umbilical cord in newborns of unimmunized mothers. The usual incubation period after birth is 3 - 10 days, which is why it is sometimes referred to as the disease of the seventh day. The newborn usually exhibits irritability, poor feeding, rigidity, facial grimacing & severe spasms with touch. The mortality rate exceeds 70%.
Physical

Arthrogryposis Meningitis, Aseptic Meningitis, Bacterial Rabies

Other Problems to Be Considered

Strychnine poisoning Dystonic drug reactions (e.g. phenothazines, metoclopramide) Hypocalcemic tetany Encephalitis Acute intra - abdominal process (due to rigid abdomen)
Laboratory Studies

Generalized tetanus : Sustained trismus may result in the characteristic sardonic smile (risus sardonicus) & persistent spasm of the back musculature may cause opisthotonus. Noise or tactile stimuli may precipitate spasms & generalized convulsions. Involvement of the autonomic nervous system may result in severe arrhythmias, oscillation of the blood pressure,

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The diagnosis of tetanus is based entirely on clinical findings. Tetanus is unlikely if a reliable history indicates the completion of a primary vaccination series & the receipt of required booster doses. Wounds should be cultured in suspected cases. However, C tetani can be cultured from wounds of patients without tetanus

& frequently cannot be cultured from wounds of patients with tetanus. The leukocyte count may be high. Cerebrospinal fluid examination yields normal results. Serum antitoxin levels of 0.01 or higher are considered protective & make tetanus unlikely, although rarely cases have been reported despite the presence of protective antitoxin levels. Serum muscle enzyme levels (e.g. creatine kinase, aldolase) may be elevated. Electromyography may show continuous discharge of motor subunits & shortening or absence of the silent interval normally observed after an action potential. Nonspecific changes may be evident on electrocardiography.

Other Tests

Medical Care

The goals of treatment in patients with tetanus include initiating supportive therapy, debriding the wound to eradicate spores & alter conditions for germination, stopping the production of toxin within the wound, neutralizing unbound toxin, controlling disease manifestations & managing complications. Initial supportive therapy : The patient should be placed in a quiet room in an ICU. If ventilation is compromised, the patient should be sedated, intubated & provided with a soft nasal feeding tube. A tracheostomy may be needed. Wound debridement & care : The possibility of developing tetanus directly correlates with the characteristics of the wound. The most susceptible wounds are grossly contaminated or caused by blunt trauma or bites. Wounds should be explored, carefully cleansed & properly debrided. Stopping toxin production : Antimicrobials are used to decrease the number of vegetative forms (source of toxin) of C tetani in the wound. The current antimicrobial drug of choice is metronidazole, with penicillin as an alternative treatment. Other antimicrobials that have been used include clindamycin,
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erythromycin, tetracycline & vancomycin. Neutralizing unbound toxin Human tetanus immunoglobulin (TIG) is recommended for treatment. A single total dose of 3000 - 6000 U is recommended for children & adults. Doses as low as 500 U are effective in infants with tetanus neonatorum. Tetanus antitoxin is administered as a single dose of 50, 000 100, 000 U after appropriate testing for sensitivity & desensitization, if necessary. Controlling disease manifestations : A benzodiazepine should be used to produce sedation, decrease rigidity & control spasms (midazolam administered intravenously at 5 - 15 mg/h is suitable). If the spasms are not controlled with benzodiazepines, long - term neuromuscular blockade is required. Managing complications : Specific therapy for autonomic system complications & control of spasms should be initiated. Sympathetic hyperactivity is treated with combined alpha & beta blockade or morphine. Epidural blockade with local anesthetics may be needed. Hypotension requires fluid replacement & dopamine or norepinephrine administration. Clinical tetanus does not induce immunity against future attacks; therefore, all patients should be fully immunized with tetanus toxoid during the convalescent period.

Diet

Patients should not be given any food by mouth because of the risk of aspiration. Nutrition should be intravenously supported. Consultation with a nutritionist is helpful.
Activity

The patient should be on bedrest in a room that can be kept dark & quiet. Even the slightest physical stimulus can cause a cycle of spasms.

29

Tuberculosis

Tuberculosis (TB) is the most common cause of infectious diseaserelated mortality worldwide. Childhood tuberculosis is a primary type of TB as infection occurs for the first time with tubercle bacilli. It is a typical granulomatous inflammation reaction seen in humans. Tuberculosis disease in infancy & childhood differs considerably from that of adults. The majority of primary TB infections are so mild that they may be completely unrecognized clinically, yet progression to frank disease is always possible at any stage in the life span. The dangers of progression are greatest in the first two years of life & for this reason treatment of every young child is desirable, no matter how mild the infection. Species - M. tuberculosis, M bovis latter is resistant to PZI. It can lie dormant.
The agents of tuberculosis,

Tuberculosis infection occurs after the inhalation of infective droplet containing M. tuberculosis. A reactive tuberculin skin test & the absence of clinical & radiographic manifestations are the hallmark of this stage (latent tuberculosis infection LTBI). Tuberculosis disease occurs when signs & symptoms or radiographic changes become apparent. The word tuberculosis refers to disease.
Mode of Transmission 1) Inhalation organisms present in fresh sputum or dried sputum

Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium microti First described by Robert Koch in 1882. Mold like appearance in culture hence the name. The cell wall is rich in lipid. When stained cell wall resists decolonization by acid. The tubercle bacilli are strict aerobes. A lipid - rich cell wall accounts for resistance to the bactericidal actions of antibody & complement. Mycobacteria grow slowly, growth can be detected in 13wk in selective liquid medium using radio labeled nutrients (the BACTEC radiometric system) & drug susceptibilities can be determined in an additional 35 days. The presence of M. tuberculosis in clinical specimens can be detected within hours using PCR.
Epidemiology
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of open case. 2) Ingestion leads to abdominal tuberculosis. 3) Inoculation occurs through skin 4) Tran placental congenital TB in fetus from infected mother. Liver is the primary site. Transmission of M. tuberculosis is person to person, usually by airborne Chance of transmission increases when the patient has an acid - fast smear of sputum, poor air circulation, adults do not transmit the organism within 2wk after beginning adequate chemotherapy, children with tuberculosis rarely infect other children
Spread of TB

1. Local spread through macrophages 2. Lymphatic spread primarily it is infection of lymphoid tissue. 3. Haematogenous spread spread through blood causing military TB. 4. By natural passages -a. From lungs to pleura b. Transbronchial spread c. Into peritoneal cavity (intestinal TB) d. Through swallowing (intestinal TB) e. Renal to bladder
Immunology

Cell mediated immunity is most important. CD4 cells are sensitized by M. Tuberculosis. It produces cytokine which activates macrophages. Cell mediated immunity protects host. Delayed Type Hyper (DTH) sensitivity causes caseous necrosis. DTH has no relation

with immunity.
Pathophysiology

lymph nodes.
Fate of primary complex

Humans are the only known reservoir for Mycobacterium tuberculosis. TB is transmitted by airborne droplets. TB exposure occurs by sharing common airspace with an individual who is in the infectious stage of TB. When inhaled, droplet nuclei are deposited within the terminal airspaces of the lung. Upon encountering the bacilli, macrophages ingest & transport the bacteria to regional lymph nodes.
The bacilli have 4 potential fates

1)

Primary focus + lymphatic drainage +lymph nodes Primary complex Good community & favorable environment Fibrosis

Calcification

1) 2) 3) 4)

They may be killed by the immune system, They may multiply & cause primary TB, They may become dormant & remain asymptomatic, or They may proliferate after a latency period (reactivation disease). Reactivation TB may occur following either (2) or (3) above. Macrophages, T lymphocytes, B lymphocytes & fibroblasts are among the cells that aggregate to form a granuloma, with lymphocytes surrounding the infected macrophages. The granuloma functions not only to prevent dissemination of the mycobacteria, but also provides a local environment for communication of cells of the immune system. Within the granuloma, T lymphocytes secrete cytokines such as interferon gamma, which activates macrophages to destroy the bacteria with which they are infected. Cytotoxic T cells can also directly kill infected cells, by secreting perforin & granulysin.

Primary TB / Ghons complex / childhood TB

Poor immunity & unfavorable environment Increased inflammation process (progressive primary TB) Consolidation (primary focus & regional lymph nodes merge) 3) Liquefaction - spitted out - cavity. 4) Nodes compress bronchus - obstructive emphysema (incomplete) - atelectasis (complete obstruction) 5) Nodes erode bronchus - TB bronchitis - bronchogenic dissemination. 6) Haematogenous spread - Simon focus in apex - metastasis 7) Caseous node erode blood vessels - miliary TB - TB meningitis. Tuberculosis in childhood constitutes a spectrum of 3 broad categories : 1) These are children who have been in contact with an open case of TB. They show no evidence of infection but may well harbor Mycobacteria at the earliest stage. They are otherwise well, tuberculin negative & with a normal chest X - ray. 2) Infected, no disease. Asymptomatic tuberculin reactors. These are children under 5 years who are tuberculin positive, but in whom there is no other evidence of TB. 3) Clinically active Here there has been progression of the primary complex & disease is clinically apparent.
Secondary tuberculosis

2)

Primary infection occurs in lungs, lymph nodes, skin or GIT. Primary complex consists of 3 components 1) Primary focus Lesion in the lung tissue at the entry of bacilli. 2) Lymphangitis The lymphatics which drain the lesion contain phagocytes with bacilli. 3) Lymphadenitis Enlarged hilar lymph nodes & trachea bronchial
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Occurs in individuals who are previously infected. May be endogenous or exogenous spread. Children above 7 yrs especially girls. Common site of lesion is apex. (Puhls lesion) Regional lymph nodes are not involved in chronic pulmonary

TB.
Clinical Pulmonary tuberculosis - Typical symptoms of pulmonary TB

Physical

include a productive cough, fever & weight loss. Patients with pulmonary TB occasionally present with hemoptysis or chest pain. Other systemic symptoms include anorexia, fatigue & night sweats. Tuberculous meningitis - Patients with tuberculous meningitis may present with a headache that is either intermittent or persistent for 2 - 3 weeks. Fever may be low - grade or absent. Skeletal TB - The most common site of skeletal TB involvement is the spine (Pott disease). Symptoms include back pain or stiffness. Tuberculous arthritis - usually involves only one joint. Although any joint may be involved, the hips & knees are affected most commonly, followed by the ankle, elbow, wrist & shoulder. Genitourinary TB - Reported symptoms of genitourinary TB include flank pain, dysuria & frequency. In men, genital TB may manifest as epididymitis or a scrotal mass. In women, genital TB may mimic pelvic inflammatory disease. Gastrointestinal TB - Any site along the gastrointestinal tract may become infected. Symptoms of gastrointestinal TB are according to the site infected, including the following : nonhealing ulcers of the mouth or anus; difficulty swallowing with esophageal disease; abdominal pain mimicking peptic ulcer disease with stomach or duodenal infection; malabsorption with infection of the small intestine; & pain, diarrhea, or hematochezia with infection of the colon. Tuberculous lymphadenitis (scrofula) - The most common site of tuberculous lymphadenitis is in the neck along the sternocleidomastoid muscle. It is usually unilateral & causes little or no pain. Cutaneous TB - Direct inoculation may result in an ulcer or wartlike lesion.
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Physical examination findings associated with TB depend on the organs involved. Patients with pulmonary TB have abnormal breath sounds, especially over the upper lobes or areas involved. Signs of extrapulmonary TB differ depending on the tissues involved. Signs may include confusion, coma, neurologic deficit, chorioretinitis, lymphadenopathy & cutaneous lesions Postnatal TB is contracted via the airborne route. The most common findings of postnatal TB include adenopathy & a lung infiltrate. However, the chest radiographic findings may be normal in infants with disseminated disease.
Laboratory Studies

In contrast to adults, Mycobacteria are excreted in a childs sputum in small number, only sporadically, or not at all. Sputum is not readily obtainable from children & gastric washing or other techniques must be used in order to obtain material. False positives are frequent on direct smear of gastric washings & results of culture may only be available after some weeks. Sputum should be collected in the early morning on 3 consecutive days. Early - morning gastric aspirate may also produce a good specimen in children. Another option is fiberoptic bronchoscopy with transbronchial biopsy & bronchial washings. Biopsy of bone marrow, liver, or blood cultures is occasionally necessary & may be helpful. Traditional mycobacterial cultures require weeks for growth & identification. Newer technologies, including ribosomal RNA probes or DNA polymerase chain reaction, allow identification within 24 hours.
Other laboratory tests

CBC count Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)

Alkaline phosphatase Total bilirubin Uric acid Creatinine HIV serology in all patients with TB. For congenital TB, the best diagnostic test is the examination of the placenta for pathology, histology & culture. Mycobacterial blood cultures of the newborn may also be helpful. Treatment may be necessary until placental culture results are negative
Other Tests 1) Tine / Monotest

A positive Tine is one where 2 or more tine papules have run together to form a larger papule or blister. All reactions less than this are negative or doubtful. A Tine is only a screening test. If the result is doubtful, a proper intradermal tuberculin test should be done.
2) Tuberculin skin testing (Mantoux test)

False + 6 9 mm + 10 14 mm ++ 15 20 mm +++ 21 30 mm ++++ > 30 mm or necrosis. False negative test Poor technique of administration Biased / misreading of results PEM Infections Drugs like steroids Immunosuppressed state. False positive test Previous BCG vaccination. Atypical mycobacterial infection.
Positive montoux test indicates prior infection by TB bacilli, but not active tuberculosis.

3 cutoff points of clinical significance exist; the criteria for each cutoff point are listed below.
a) Larger than or equal to 5 mm

Grade

It is the most widely available test for diagnosing tuberculous infection in the absence of active disease (latent infection). The tuberculin skin test involves an intradermal injection of 5 tuberculin units (0.1ml of PPD) of purified protein derivative. In reaction to this T cells which were sensitized by prior infection accumulate at the site & release lymphokines which produce induration, local vasodilation & edema. The response is measured as the amount of induration at 48 72 hours. The size of induration, rather than erythema, is diagnostic. Interpretation of skin testing depends on the size of induration, age & patient risk factors. The tuberculin skin test is not a sensitive test for active TB.
size of induration

b)

Close contacts to persons with newly diagnosed TB Persons with HIV infection Patients with organ transplant or patients who are taking the equivalent of more than 15 mg/d of prednisone for one month or more Patients with fibrotic lesions on chest radiography (not granulomas)
Larger than or equal to 10 mm

Interpretation

100

< 5mm

Patients with medical conditions that increase the risk of TB (e.g. diabetes mellitus, hematologic malignancies, carcinoma of the head & neck, intravenous drug use [known to be HIV negative], end - stage renal disease, silicosis, malnutrition, jejunoileal bypass, gastrectomy) Recent converter - At least 10 - mm increase in skin test in past 2 years (regardless of age) Recent immigrants (within 5 y) from a high - prevalence country

Children younger than 4 years exposed to adults at high risk for TB Residents & employees of facilities for long - term care, including correctional institutions, nursing homes, homeless shelters & mental institutions
Larger than or equal to 15 mm

different observers. Chest radiographs may show a patchy or nodular infiltrate (as seen in the image below). TB may be found in any part of the lung, but upper - lobe involvement is most common. The lordotic view may better demonstrate apical abnormalities.

c)

Tuberculosis

Persons with none of the above TB may be discovered incidentally in association with other chronic disorders such as HIV infection & malaria. Any patient with HIV should be suspected of having TB & an intensive search made for clinical & laboratory evidence. 3) Heaf test - Useful for mass testing. Multiple puncture test using spring loaded gun technique. Intradermal shots given & reading is taken between 3 7 days. Grades Negative - ertyhema without induration Grade 1 - popular induration at least 4 sites. Grade 2 - ring formation of at least 6 sites. Grade 3 - plaque formation Grade 4 - vesicle formation or ulceration. 4) AFB sputum test In children sputum production is nil or minimal. Hence detection of bacilli by AFB staining & culture by gastric aspirate, urine etc. should be done. 5) BACTEC radiometric system Mycobacterial growth can be detected in 1 - 3 wks. 6) PCR Using DNA or RNA probes, M tuberculi can be detected in hours.
7) Chest X - ray

This radiograph shows a patient with typical radiographic findings of tuberculosis.

Tuberculosis

PA view showing collapse consolidation of right upper lobe, hilar lymphadenopathy Changes, such as large hilar glands, with or without infiltrates in the lungs, a miliary pattern, or narrowed airways, are virtually diagnostic of TB. A lateral film is essential to assess hilar nodes. There is a wide grey zone of X - ray changes which may or may not represent TB & are often interpreted differently by
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This radiograph shows a patient with typical Primary TB is more likely to mimic the appearance of routine community - acquired pneumonia on chest radiography; in contrast to reactivation T. B. either may be associated with pleural effusion or cavitation. Various patterns may be seen, as follows : o Cavity formation indicates advanced infection & is associated with a high bacterial load. o Noncalcified round infiltrates may be confused with lung carcinoma. o Homogeneously calcified nodules (usually 5 - 20 mm) are tuberculomas & represent old infection rather than active disease. o Miliary TB is characterized by the appearance of numerous small nodular lesions that resemble millet seeds on chest radiography. CT scanning of the chest may help to better define abnormalities in patients with vague findings on chest radiography. The following are the factors to be considered : symptoms : cough, fever, tiredness etc., have many other causes. Signs : painless lymph node enlargement, wheezing & other chest signs may or may not be present. Poor weight gain or weight loss : very common in many communities for other reasons. History of contact : A history of possible contact with TB is

elicited very frequently. A reactive tuberculin test : A positive reaction indicates that infection with tubercle bacilli has occurred. But it does not necessarily mean that active disease is present. A mildly positive reaction in a malnourished or immuno compromised child should always be viewed with suspicion. But a negative reaction certainly does not rule out the presence of active tuberculous disease. Another source of confusion is the almost universal administration of BCG vaccination which induces variable skin reactivity for at least two years. In extensive or disseminated disease, i.e. Marked nodal enlargement or consolidation Bronchopneumonic spread Bone/joint Abdominal & glandular 6 months of treatment is required. This is achieved by extending the period on INH & RIF to 4 MONTHS.

contained in tablets which may be chewed or dissolved in 5 ml of water. This is followed by INH & RIF for a further 4 MONTHS as recommended by WHO but may not be essential if the child has no localizing signs of TB & responds well to the 2 months of treatment. Treatment is given daily, or at least 5 days a week, under supervision (Directly Observed Therapy, Short Course - DOTS) Thrice weekly regimens requiring higher drug dosages may be used where the more desirable daily schedules are not possible. A 4th drug - ethionamide, ethambutol, or streptomycin is added for part or all of the 6 month period in the case of Miliary disease, Meningitis, Re - treatment or Suspected resistance Finally children at risk & those infected, with no disease should receive INH & RIF under direct observation for 3 months, or if no supervision is possible, INH only for 3 - 6 months.

30
Typhoid fever

Treatment

Effective with minimal toxicity Isoniazid, Streptomycin, Rifampicin, Pyrazinamide, Ethambutol Second line drugs Cycloserine, Ethionamide, PAS, Capreomycin, Kanamycin Others - These are used in drug resistant case Quinolones, Rifamycin, Amikacin, Imipenem, Ampicillin Bactericidal rifampicin (R), isoniazid (INH), pyrazinamide (P), streptomycin (S)
Bacteriostatic

Drugs First line drugs -

Ethambutol (E), PAS All children diagnosed with probable TB should receive INH, RIF & PZA for the initial 2 months. These are now easy to administer as special formulations are available for children. The drugs are
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Typhoid fever, also known as enteric fever, is a potentially fatal multisystem illness caused primarily by Salmonella typhi. S. paratyphi A, S. paratyphi B & S paratyphi C can cause paratyphoid fever in humans. S typhi has been a major human pathogen for thousands of years, thriving in conditions of poor sanitation, crowding & social chaos. The name S typhi is derived from the ancient Greek typhos, an ethereal smoke or cloud that was believed to cause disease & madness. In the advanced stages of typhoid fever, the patients level of consciousness is truly clouded. The classic presentation includes step ladder type fever, relative bradycardia, leucopenia, rose spots, malaise, diffuse abdominal pain & constipation. If untreated, typhoid fever is a serious illness that may progress to delirium, obtundation, intestinal hemorrhage, bowel perforation & death.

Etiology

S typhi has no nonhuman vectors. The following are modes of transmission : Oral transmission via food or beverages handled by an individual who chronically sheds the bacteria through stool or, less commonly, urine Hand - to - mouth transmission after using a contaminated toilet & neglecting hand hygiene Oral transmission via sewage - contaminated water or shellfish
Pathophysiology

extension of S typhi infected bile. The result is that the organism re - enters the gastrointestinal tract in the bile & reinfects Peyer patches. Bacteria that do not reinfect the host are typically shed in the stool & are then available to infect other hosts. S typhi are able to survive a stomach pH as low as 1.5. Antacids, histamine - 2 receptor antagonists (H2 blockers), proton pump inhibitors, gastrectomy & achlorhydria decrease stomach acidity & facilitate S typhi infection. Environmental & behavioral risk factors that are independently associated with typhoid fever include eating food from street vendors, living in the same household with someone who has new case of typhoid fever, washing the hands inadequately, sharing food from the same plate, drinking unpurified water & living in a household that does not have a toilet. Most documented typhoid fever cases involve school - aged children & young adults. However, the true incidence among very young children & infants is thought to be higher. The presentations in these age groups may be atypical, ranging from a mild febrile illness to severe convulsions & the S typhi infection may go unrecognized.

Risk factors

The incubation period is 14 days with a range limit of 3 to 60 days. All pathogenic Salmonella species are engulfed by phagocytic cells, which then pass them through the mucosa & present them to the macrophages in the lamina propria. Nontyphoidal salmonellae are phagocytized throughout the distal ilium & colon. In contrast to the nontyphoidal salmonellae, S typhi enters the hosts system primarily through the distal ilium. S typhi has specialized fimbriae that adhere to the epithelium over clusters of lymphoid tissue in the ilium (Peyer patches), the main relay point for macrophages traveling from the gut into the lymphatic system. The bacteria then induce their host macrophages to attract more macrophages. It co - opts the macrophages cellular machinery for their own reproduction as it is carried through the mesenteric lymph nodes to the thoracic duct & the lymphatics & then through to the reticuloendothelial tissues of the liver, spleen, bone marrow & lymph nodes. Once there, the S typhi bacteria pause & continue to multiply until some critical density is reached. Afterward, the bacteria induce macrophage apoptosis, breaking out into the bloodstream to invade the rest of the body. The gallbladder is then infected via either bacteremia or direct
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Age

History

A severe nonspecific febrile illness in a patient who has been exposed to S typhi should always raise the diagnostic possibility of typhoid fever (enteric fever).
Classic typhoid fever syndrome

Typhoid fever begins 7 - 14 days after ingestion of S typhi. The fever pattern is stepwise, characterized by a rising temperature over the course of each day that drops by the subsequent morning.

Over the course of the first week of illness, the notorious gastrointestinal manifestations of the disease develop. These include diffuse abdominal pain & tenderness and, in some cases, fierce colicky right upper quadrant pain. Monocytic infiltration inflames Peyer patches & narrows the bowel lumen, causing constipation that lasts the duration of the illness. The individual then develops a dry cough, dull frontal headache, delirium & an increasingly stuporous malaise At approximately the end of the first week of illness, the fever plateaus at 103 - 104F (39 - 40C). The patient develops rose spots, which are salmon - colored, blanching, truncal, maculopapules usually 1 - 4 cm wide & fewer than 5 in number; these generally resolve within 2 - 5 days. The tongue is often coated in the centre (coated tongue)and is clear at the margins. These are bacterial emboli to the dermis & occasionally develop in persons with shigellosis or nontyphoidal salmonellosis. During the second week of illness, the signs & symptoms listed above progress. The abdomen becomes distended & soft splenomegaly is common. Relative bradycardia & dicrotic pulse (double beat, the second beat weaker than the first) may develop. In the third week, the still febrile individual grows more toxic & anorexic with significant weight loss. The conjunctivae are infected & the patient is tachypneic with a thready pulse & crackles over the lung bases. Abdominal distension is severe. Some patients experience foul, green - yellow, liquid diarrhea (pea soup diarrhea). The individual may descend into the typhoid state, which is characterized by apathy, confusion & even psychosis. Necrotic Peyer patches may cause bowel perforation & peritonitis. This complication is often unheralded & may be masked by corticosteroids. At this point, overwhelming toxemia, myocarditis, or intestinal hemorrhage may cause death. If the individual survives to the fourth week, the fever, mental
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state & abdominal distension slowly improve over a few days. Intestinal & neurologic complications may still occur in surviving untreated individuals. Weight loss & debilitating weakness last months. Some survivors become asymptomatic S typhi carriers & have the potential to transmit the bacteria indefinitely.
Various presentations of typhoid fever

The clinical course of a given individual with typhoid fever may deviate from the above description of classic disease. The timing of the symptoms & host response may vary based on geographic region, race factors & the infecting bacterial strain. The stepladder fever pattern that was once the hallmark of typhoid fever now occurs in as few as 12% of cases. In most contemporary presentations of typhoid fever, the fever has a steady insidious onset. Young children, individuals with AIDS & one third of immunocompetent adults who develop typhoid fever develop diarrhea rather than constipation. In addition, in some localities, typhoid fever is generally more apt to cause diarrhea than constipation. Atypical manifestations of typhoid fever include isolated severe headaches that may mimic meningitis, acute lobar pneumonia, isolated arthralgias, urinary symptoms, severe jaundice, or fever alone. Some patients, especially in India & Africa, present primarily with neurologic manifestations such as delirium or, in extremely rare cases, Parkinsonian symptoms or Guillain - Barr syndrome. Other unusual complications include pancreatitis, meningitis, orchitis, osteomyelitis & abscesses anywhere on the body.

Treated typhoid fever

If appropriate treatment is initiated within the first few days of full - blown illness, the disease begins to remit after about 2 days & the patients condition markedly improves within 4 - 5 days. Any

delay in treatment increases the likelihood of complications & recovery time.

Laboratory Studies

The diagnosis of typhoid fever (enteric fever) is primarily clinical. Culture o The criterion standard for diagnosis of typhoid fever has long been culture isolation of the organism. Cultures are widely considered 100% specific. o Blood, intestinal secretions (vomitus or duodenal aspirate) & stool culture results are positive for S typhi in approximately 85% - 90% of patients with typhoid fever who present within the first week of onset. They decline to 20% - 30% later in the disease course. In particular, stool culture may be positive for S typhi several days after ingestion of the bacteria secondary to inflammation of the intraluminal dendritic cells. Later in the illness, stool culture results are positive because of bacteria shed through the gallbladder. Polymerase chain reaction (PCR) : PCR has been used for the diagnosis of typhoid fever with varying success. The Widal test was the mainstay of typhoid fever diagnosis for decades. It is used to measure agglutinating antibodies against H & O antigens of S typhi. Neither sensitive nor specific, the Widal test is no longer an acceptable clinical method. Other nonspecific laboratory studies o Most patients with typhoid fever are moderately anemic, have an elevated erythrocyte sedimentation rate (ESR), thrombocytopenia & relative lymphopenia. o Most also have a slightly elevated prothrombin time (PT) & activated partial thromboplastin time (aPTT) & decreased fibrinogen levels. o Liver transaminase & serum bilirubin values usually rise to twice the reference range. o Mild hyponatremia & hypokalemia are common.
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A serum alanine amino transferase (ALT)tolactate dehydrogenase (LDH) ratio of more than 9 :1 appears to be helpful in distinguishing typhoid from viral hepatitis. A ratio of greater than 9 :1 supports a diagnosis of acute viral hepatitis, while ratio of less than 9 :1 supports typhoid hepatitis. Radiography : Radiography of the kidneys, ureters & bladder (KUB) is useful if bowel perforation (symptomatic or asymptomatic) is suspected. CT scanning & MRI : These studies may be warranted to investigate for abscesses in the liver or bones, among other sites.

Imaging Studies

Procedures

Bone marrow aspiration : The most sensitive method of isolating S typhi is BMA culture.
Staging

The proper treatment approach to typhoid fever depends on whether the illness is complicated or uncomplicated. Complicated typhoid fever is characterized by melena, serious abdominal discomfort, intestinal perforation, marked neuropsychiatric symptoms, or other severe manifestations. Depending on the adequacy of diagnosis & treatment, complicated disease may develop in up to 10% of treated patients. Delirium, obtundation, stupor, coma, or shock demands a particularly aggressive approach.
Medical Care

Treatment should not be delayed for confirmatory tests since prompt treatment drastically reduces the risk of complications & fatalities. Antibiotic therapy should be narrowed once more information is available. Compliant patients with uncomplicated disease may be treated on an outpatient basis. They must be advised to use strict handwashing techniques & to avoid preparing food for others during the illness course. Hospitalized patients should be placed in contact isolation during the acute phase of the infection. Feces & urine must be disposed

of safely.
Surgical Care

Trimethoprim & sulfamethoxazole

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. < 2 months : Do not administer > 2 months : 15 - 20 mg/kg/d PO, based on TMP, tid/qid for 14 d
Cefotaxime

Surgery is usually indicated in cases of intestinal perforation. If antibiotic treatment fails to eradicate the hepatobiliary carriage, the gallbladder should be resected.
Antibiotics History of antibiotic resistance

Chloramphenicol was used universally to treat typhoid fever from 1948 until the 1970s, when widespread resistance occurred. Ampicillin & trimethoprim - sulfamethoxazole (TMP - SMZ) then became treatments of choice. However, in the late 1980s, some S typhi & S paratyphi strains (multidrug resistant [MDR] S typhi or S paratyphi) developed simultaneous plasmid - mediated resistance to all three of these agents. Fluoroquinolones are now the most recommended antibiotics for the treatment of typhoid fever. They are highly effective against susceptible organisms, yielding a better cure rate than cephalosporins. Unfortunately, resistance to first - generation fluoroquinolones is widespread in many parts of Asia. For empiric treatment of uncomplicated typhoid fever, the IAP recommends cefixime and, as a second - line agent, azithromycin. For complicated typhoid fever, they recommend ceftriaxone. Aztreonam & imipenem are second - line agents for complicated cases.
Chloramphenicol

Arrests bacterial cell wall synthesis, which inhibits bacterial growth. 200 mg/kg/d IV in divided doses for 14 d Infants & children : 50 - 180 mg/kg/d IV/IM divided q4 - 6h > 12 years : Administer as in adults
Azithromycin

Treats mild to moderate microbial infections. < 6 months : Not established > 6 months Day 1 : 10 mg/kg PO once; not to exceed 500 mg/d Days 2 - 5 : 5 mg/kg PO qid; not to exceed 250 mg/d
Ceftriaxone

Third - generation cephalosporin with broad - spectrum gram negative activity against gram - positive organisms; > 7 days : 25 - 50 mg/kg/d IV/IM; not to exceed 125 mg/d Infants & children : 50 - 75 mg/kg/d IV/IM divided q12h; not to exceed 2 g/d

Binds to 50S bacterial - ribosomal subunits & inhibits bacterial growth by inhibiting protein synthesis. 50 - 75 mg/kg/d PO/IV divided q6h
Amoxicillin

31 32 33 Chicken pox

Chickenpox is caused by the varicella - zoster virus. The varicella - zoster virus is a member of the human herpesvirus subfamily Alphaherpesvirinae and, as is true of all herpes viruses, is a

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. 20 - 50 mg/kg/d PO divided q8h for 14 d
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DNA virus. Varicella is highly contagious; secondary attack rates range from 80 - 90% for household contacts. The disease is generally regarded as a mild, self - limiting viral illness with occasional complications. The disease presents with fever & blistered rash. The virus then remains latent or dormant in the body. Among the most serious complications are varicella pneumonia & encephalitis. Household transmission rates are 80 - 90%. Second cases within the household are often more severe. Children who are susceptible rarely acquire the disease by contact with adults with zoster. Maximum transmission occurs during late winter & spring. Varicella is associated with humoral & cell - mediated immune responses. These responses induce long - lasting immunity. Repeat subclinical infection can occur in these persons, but second attacks of chickenpox are extremely rare in immunocompetent persons. Re - exposure & subclinical infections may serve to boost the immunity acquired after an episode of chicken pox. Herpes Zoster (Shingles) is a painful localized rash caused by the varicella virus. In children who have recovered from chickenpox, the virus remains inactive (dormant) in certain nerve roots & can be activated spontaneously after several months or years. It may occur on the trunks or limbs & characteristically involves only one side of the trunk. The rash is similar to the rash of chicken pox (fluid filled blisters) but is more crowded & extremely painful. Shingles usually afflicts adults especially old people.

Pathophysiology

The varicella - zoster virus enters through the respiratory system & colonizes the upper respiratory tract. The virus initially replicates in the regional lymph nodes; 4 - 6 days later, a primary viremia spreads the virus to reticuloendothelial cells in the spleen, liver & elsewhere. After a week, a secondary viremia disseminates the virus to the viscera & skin, eliciting the typical skin lesions. This viremia also spreads the virus to respiratory sites & is responsible for the contagion of varicella before the appearance of the rash. Infection of the CNS or liver also occurs at this time.

Mortality / Morbidity

Most deaths are from associated encephalitis, pneumonia, secondary bacterial infection & Reye syndrome. The mortality rate in children who are immunocompromised is much higher. The disease can be serious in neonates, depending on the timing of infection in the mother.
Age

The maximum incidence of varicella in unvaccinated populations is in children aged 1 - 6 years. Persons older than 14 years account for 10% of varicella cases.
Transmission

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An example of varicella is shown in the image below. The pleomorphic rash characteristic of varicella Papules, vesicles & pustules are concurrently present.

Transmission involves the following : Transmission occurs mainly through respiratory droplets that contain the virus, making the disease highly contagious even before the rash appears. Papules & vesicles, but not the crusts, have high populations of the virus. The infectious period begins 2 days before skin lesions appear & ends when the lesions crust, usually 5 days later. Direct person - to - person contact with lesions also spreads the virus.

Maternal varicella with viremia can transplacentally spread to the fetus. This leads to neonatal varicella.

Risk factors Neonatal period

o o o
o o o o o o

Prodrome

A neonates first month of life is a susceptible period for severe varicella, especially if the mother is seronegative. Delivery before 28 weeks gestation also makes a baby susceptible because transplacental transfer of immunoglobulin G (IgG) antibodies occurs after this time. Steroid therapy : High doses (i.e. doses equivalent to 1 - 2 mg/ kg/d of prednisolone) for 2 weeks or more are definite risk factors for severe disease. Even short - term therapy at these doses immediately preceding or during the incubation period of varicella can cause severe or fatal varicella. Malignancy : All children with cancer have an increased risk for severe varicella. The risk is highest for children with leukemia. Immunocompromised state (e.g. malignancy, anti malignancy drugs, human immunodeficiency virus [HIV], other congenital or acquired immunodeficient conditions) : Defects of cellular but not humoral immunodeficiency make a person susceptible to severe varicella. The following may be noted with varicella :

Adolescence & adulthood

Low - grade fever preceding skin manifestations by 1 - 2 days Some children complain of abdominal pain Rash, usually starting on the head & trunk & spreading to the rest of the body Typically, complaints of intense pruritus Headache Malaise Anorexia Cough & coryza Sore throat
Rash

Physical

o o
o o o o o o o o o

History

Exposure

Varicella spreads primarily by airborne droplets. The infectious particles are cell - free virus particles derived from skin lesions or the respiratory tract. The disease is infectious a day before the rash appears. Most patients have a history of exposure in the home, daycare center, or school. Incubation : The incubation period is typically 10 - 14 days, although it may extend to 21 days.

The characteristic rash appears in crops. An otherwise healthy child usually has 250 - 500 lesions but may have as few as 10 or as many as 1500. Each lesion starts as a red macule & passes through stages of papule, vesicle, pustule & crust. Redness or swelling around a lesion should lead to suspicion of bacterial superinfection. The vesicle on a lesions erythematous base leads to its description as a pearl / dewdrop on a rose petal. The hallmark is the simultaneous presence of different stages of the rash. Some lesions may appear in the oropharynx. Eye lesions are rare. New lesions continue to erupt for 3 - 5 days. Lesions usually crust by 6 days (range 2 - 12 d) & completely heal by 16 days (range 7 - 34 d). Prolonged eruption of new lesions or delayed crusting & healing can occur with impaired cellular immunity.
Fever

o
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Fever is usually low grade (100 - 102F) but may be as high as 106F.

o o

In otherwise healthy children, fever typically subsides within 4 days. Prolonged fever should prompt suspicion of complication or immunodeficiency. In utero infection : Outcomes of in utero varicella infections vary based on the timing of the infection.
Congenital varicella syndrome

antibodies along with the virus. Full - term neonates of these women usually have mild varicella because of the attenuating effect of the transplacentally acquired antibodies.
Differential Diagnoses

Congenital varicella syndrome occurs in 2% of children born to women who develop varicella during the first or second trimester of pregnancy. This syndrome manifests as intrauterine growth retardation, microcephaly, cortical atrophy, limb hypoplasia, microphthalmia, cataracts, chorioretinitis & cutaneous scarring.
Infantile zoster

Contact Dermatitis Enteroviral Infections Herpes Simplex Virus Infection Impetigo Urticaria Measles Drug reactions Insect bites
Laboratory Studies

Infantile zoster usually manifests within the first year of life. The cause is maternal varicella infection after the 20 weeks gestation. Infantile zoster commonly involves the thoracic dermatomes.
Neonatal varicella

Neonatal varicella can be a serious illness, depending on the timing of maternal varicella & delivery. After the initial viremia, the mother develops antibodies against the varicella virus. The severity of the disease in the newborn depends on whether transplacental passage includes only the virus or includes both the virus & the antibodies. If the mother develops varicella within 5 days before or 2 days after delivery, the baby is exposed to the secondary viremia of the mother. The baby transplacentally acquires the virus but acquires no protective antibodies because of insufficient time for antibodies to develop in the mother. Prophylaxis or treatment is required with varicella - zoster immune globulin (VZIG) & acyclovir. Onset of maternal varicella more than 5 days antepartum provides the mother sufficient time to manufacture & pass on
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Laboratory studies are unnecessary for diagnosis because varicella is clinically obvious. Most children with varicella have leucopenia in the first 3 days, followed by leucocytosis. Marked leucocytosis may indicate a secondary bacterial infection but is not a dependable sign. Most children with significant secondary bacterial infections do not have leucocytosis. Immunohistochemical staining of skin lesion scrapings can confirm varicella. Polymerase chain reaction (PCR) examination of skin scrapings is quick & sensitive.
Imaging Studies

Chest radiography may be indicated. Children with high temperatures & respiratory signs should have chest radiography to confirm or exclude pneumonia. Chest radiographic findings may be normal or may show diffuse bilateral nodular infiltrates in primary varicella pneumonia. Radiography may also detect focal infiltrates suggestive of secondary bacterial pneumonia.

Other Tests Lumbar puncture

Children with neurological signs should have their cerebrospinal fluid (CSF) examined.
Medical Care

Manage pruritus in patients with varicella with cool compresses & regular bathing. Discourage scratching to avoid scarring. Trimming the childs fingernails & having the child wear mittens while sleeping may reduce scratching. Children who develop severe & life - threatening varicella complications may require hospitalization in an ICU.
Diet

encephalitis, pneumonia) & for immunocompromised individuals with varicella. 80 mg/kg/d PO divided in 4 - 5 doses for 5 d; not to exceed 3200 mg/d Fever is usually low grade but may be elevated. Acetaminophen is probably the safest drug to use for this purpose. Salicylate usage for varicella is associated with Reye syndrome; therefore, never prescribe these agents. Nonsteroidal anti - inflammatory drugs (NSAIDs) have been suspected of suppressing immune function & promoting infection progress in patients infected with invasive group A streptococci.
Diphenhydramine

Advise parents to provide a full & unrestricted diet to the child. Some children with varicella have reduced appetite & should be encouraged to take sufficient fluids to maintain hydration. Adequate hydration is especially important if the child is receiving acyclovir because the drug can crystallize in the renal tubules if administered to dehydrated individuals.
Activity

Antihistamine has a sedating effect & is effective for pruritus 5 mg/kg/d PO divided tid/qid; not to exceed 300 mg/d

34
Diphtheria

No activity restrictions are needed for young children with uncomplicated varicella.
Medication Antiviral

Chicken pox is usually a benign disease in children & almost all children recover uneventfully. Other groups that require specific treatment are children who are immunocompromised, those who are otherwise at risk for severe disease & those who already have severe disease. Acyclovir is the drug of choice for these situations.
Acyclovir

Antiviral that acts by inhibiting herpes virus DNA polymerase & terminating viral replication. It reduces the number of lesions & duration of fever if started within 24 h of appearance of rash. It does not affect incidence of pruritus, complications, or secondary transmission. It is always used for complications of varicella (e.g.
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Diphtheria manifests as either an upper respiratory tract or cutaneous infection & is caused by the aerobic gram - positive bacteria, Corynebacterium diphtheria. The 3 isolated strains of C diphtheria include gravis, intermedius & mitis. The infection usually occurs in the spring or winter months. It is communicable for 2 - 6 weeks without antibiotic treatment. Children who are most susceptible to infection are those who are not completely immunized or have low antitoxin antibody levels & have been exposed to a carrier or diseased individual. A carrier is someone whose cultures are positive for the diphtheria species but does not exhibit signs & symptoms. C diphtheria is a nonencapsulated, nonmotile, gram - positive bacillus. Pathogenic strains can result in severe localized upper respiratory infection, localized cutaneous infections & rarely systemic infection.

Pathophysiology

History

Overcrowding, poor health, substandard living conditions, incomplete immunization & immunocompromised states facilitate susceptibility to diphtheria & are risk factors associated with transmission of this disease. Human carriers are the main reservoir of infection. Infected patients & asymptomatic carriers can transmit C diphtheria via respiratory droplets, nasopharyngeal secretions & rarely fomites. In the case of cutaneous disease, contact with wound exudates may result in the transmission of the disease to the skin as well the respiratory tract. Immunity from exposure or vaccination wanes over time. Inadequate boosting of previously vaccinated individuals may result in increased risk of acquiring the disease from a carrier, even if adequately immunized previously. C diphtheria adheres to mucosal epithelial cells where the exotoxin, released by endosomes, causes a localized inflammatory reaction followed by tissue destruction & necrosis. Local tissue destruction enables the toxin to be carried lymphatically & hematologically to other parts of the body. Elaboration of the diphtheria toxin may affect distant organs such as the myocardium, kidneys & nervous system.
Mortality / Morbidity

The most widely quoted diphtheria mortality rate is 5 - 10%. It may reach higher than 20% in children younger than 5 years & adults older than 40 years. Immunization patterns have the most influence on mortality patterns. Most deaths occur on days 3 - 4 secondary to asphyxia with a pharyngeal membrane or due to myocarditis.
Age

Onset of symptoms of respiratory diphtheria typically follows an incubation period of 2 - 5 days (range, 1 - 10 days). Symptoms initially are general & nonspecific, often resembling a typical viral upper respiratory infection (URI). Respiratory involvement typically begins with sore throat & mild pharyngeal inflammation. Development of a localized or coalescing pseudo membrane can occur in any portion of the respiratory tract. The pseudo membrane is characterized by the formation of a dense, gray debris layer composed of a mixture of dead cells, fibrin, RBCs, WBCs & organisms; Removal of the membrane reveals a bleeding, edematous mucosa. The distribution of the membrane varies from local (e.g. tonsillar, pharyngeal) to widely covering the entire tracheobronchial tree. The membrane is intensely infectious & droplet & contact precautions must be followed when examining or caring for infected patients. A combination of cervical adenopathy & swollen mucosa imparts a bulls neck appearance to many of the infected patients The most frequent cause of death is airway obstruction or suffocation following aspiration of the pseudo membrane. Cutaneous diphtheria is a disease characterized by indolent, nonhealing ulcers covered with a gray membrane. The ulcers are often co - infected with Staphylococcus aureus & group A streptococci. The lesions of cutaneous diphtheria are infectious & bacteria from cutaneous lesions have been found to cause pharyngeal infections & thus serve as a reservoir for infection.
Clinical

o o o
111

Historically, diphtheria has been primarily a disease of childhood, affecting populations younger than 12 years. Infants become susceptible to the disease at age 6 - 12 months after their transplacentally derived immunity wanes

Patients with diphtheria may present with the following complaints Low - grade fever (rarely > 103F)and chills Malaise, weakness, prostration Sore throat

o o o o o

Headache Cervical lymphadenopathy & respiratory tract pseudo membrane formation Serosanguineous or seropurulent nasal discharge, white nasal membrane Hoarseness, dysphagia Dyspnea, respiratory stridor, wheezing, cough Respiratory diphtheria may quickly progress to respiratory failure due to airway obstruction or aspiration of pseudo membrane into the tracheobronchial tree. Cutaneous diphtheria often develops at a site of previous trauma or a primary dermatologic disease. It follows an indolent course, typically lasting weeks to months. Occasionally, it may cause respiratory diphtheria.

Physical General Patient has a low - grade fever but is toxic in appearance & also may have a swollen neck. Pharyngeal diphtheria

Patients may present with general symptoms of fever, halitosis, tachycardia & anxiety. Tonsils & pharynx : Pharyngeal erythema & edema, thick, gray, leathery membrane variably covers the tonsils, soft palate, oropharynx, nasopharynx & uvula. Attempts at scraping the pseudo membrane causes bleeding of the underlying mucosa. Neck : Extensive anterior & submandibular cervical lymphadenopathy imparts a bulls neck appearance. The patient may hold his or her head in extension. It can occasionally also be associated with dysphonia. Respiratory distress manifesting as stridor, wheezing, cyanosis, accessory muscle use & retractions. Cardiac toxicity typically occurs after 1 - 2 weeks of illness following improvement in the pharyngeal phase of the disease. It may
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manifest as follows : Myocarditis is seen in as many as 60% of patients (especially if previously unimmunized) & can present acutely with congestive heart failure (CHF), circulatory collapse, or more subtly with progressive dyspnea, diminished heart sounds, cardiac chamber dilatation & weakness. Neurologic toxicity is proportional to the severity of the pharyngeal infection. Most patients with severe disease develop neuropathy. Deficits include the following : Cranial nerve deficits including oculomotor, ciliary paralysis, facial & pharyngeal, or laryngeal nervous dysfunction. Occasionally, a stocking & glove peripheral sensory neuropathy pattern can be observed. Peripheral neuritis develops anywhere from 10 days to 3 months after the onset of pharyngeal disease. It manifests initially as a motor defect of the proximal muscle groups in the extremities extending distally. Cutaneous diphtheria begins as a painful lesion resembling an erythematous pustule, which breaks down to form an ulcer covered with a gray membrane. The following factors may predispose to diphtheria infection : Incomplete or absent immunization, which is especially important in the adult population & as well the pediatric population in underdeveloped countries, may predispose to infection. In some cases, immunity does not prevent infection but lessens the severity of the disease. Antitoxin titers decrease over time & immunity wanes, thus older people who have not received booster vaccination are more susceptible to contract the disease from carriers. Low herd immunity, possibly leading to increasing prevalence of diphtheria infections Immunocompromised states - Due to pharmacologic immune suppression, disease states including HIV, or relative

Causes

compromise such as from diabetes or alcoholism Low socioeconomic status Pharyngitis Peritonsillar Abscess Pharyngitis Retropharyngeal Abscess Rheumatic Fever Shock, Septic Tonsillitis Septic arthritis Sepsis

Procedures

Differential diagnosis

Angioedema Endocarditis Mononucleosis Myocarditis Oropharyngeal / esophageal candidiasis Epiglottitis Peripheral nerve palsies Acute renal failure
Laboratory Studies

Endotracheal intubation Surgical airway - Cricothyroidotomy or tracheostomy Laryngoscopy, bronchoscopy as indicated in intubated patients Electrical pacing for high - grade conduction disturbances

Pre hospital Care

Careful assessment of airway patency & cardiovascular stability. Patients should be transported to the nearest hospital.
Emergency Care

To establish the diagnosis of C diphtheriae, it is vital to both isolate C diphtheriae in culture media & to identify the presence of toxin production. Polymerase chain reaction (PCR) assays for detection of DNA sequence encoding the A subunit of tox+ strain are both rapid & sensitive. Once diphtheria infection has been established, the Centers for Disease Control & Prevention (CDC) should be contacted & further testing may be requested.
Other laboratory studies

CBC may show moderate leukocytosis. Urinalysis (UA) may demonstrate transient proteinuria. Serum troponin I levels seem to correlate with the severity of myocarditis. Chest radiograph & soft tissue neck radiography/CT or ultrasonography may show prevertebral soft tissue swelling, enlarged epiglottis & narrowing of the subglottic region. ECG may show ST - T wave changes, variable heart block & dysrhythmia.

Imaging Studies

Treatment of diphtheria should be initiated even before confirmatory tests are completed due to the high potential for mortality & morbidity. Isolate all cases promptly & use universal & droplet precautions to limit the number of possible contacts. Secure definite airway for patients with impending respiratory compromise or the presence of laryngeal membrane. Early airway management allows access for mechanical removal of tracheobronchial membranes & prevents the risk of sudden asphyxia through aspiration. Consider involving ENT or operating room personnel for intubation & securing of airway if there is suspicion for loss of the airway or respiratory failure. Maintain close monitoring of cardiac activity for early detection of rhythm abnormalities. Initiate electrical pacing for clinically significant conduction disturbance & provide pharmacologic intervention for arrhythmias or for heart failure. Provide 2 large - bore IVs for patients with a toxic appearance; provide invasive monitoring & aggressive resuscitation for patients with septicemia. Initiate prompt antibiotic coverage (erythromycin or penicillin) for eradication of organisms, thus limiting the amount of toxin production. Antibiotics hasten recovery & prevent the spread of the disease to other individuals. Neutralize the toxin as soon as diphtheria is suspected. Diphtheria antitoxin is a horse - derived hyper immune
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antiserum that neutralizes circulating toxin prior to its entry into the cells. It prevents the progression of symptoms. Diphtheria disease does not confer immunity; thus, initiation or completion of immunization with diphtheria toxoid is necessary. Obtain throat & nasal swabs from persons in close contact with the suspected diphtheria victim; administer age - appropriate diphtheria booster. Initiate antibiotic therapy with erythromycin or penicillin for chemoprophylaxis in a patient with suspected exposure. Throat cultures should be repeated in 2 weeks after treatment.

Medication

Patients with active disease as well as all close contacts should be treated with antibiotics. Treatment is most effective in the early stages of disease & decreases the transmissibility & improves the course of diphtheria. Additionally, close contacts, such as family members, household contacts & potential carriers, must receive chemoprophylaxis regardless of immunization status or age. The CDC has approved macrolide such as erythromycin as first - line agents for patients older than 6 months of age. However, macrolide therapy has been associated with an increase in pyloric stenosis in children younger than 6 months, especially treatment with erythromycin. Intramuscular penicillin is recommended for patients who will be noncompliant or intolerant to an erythromycin course. The horse serum antitoxin is given to anyone suspected to have diphtheria & can be administered without confirmation from cultures, as it is most efficacious early during the course of the disease.
Antitoxins

Neutralizes toxin before it enters cells. Dose given depends on site of infection & length of time patient is symptomatic 20, 000 - 40, 000 U IV over 60 min for laryngeal or pharyngeal disease of < 48 h duration 40, 000 - 60, 000 U for nasopharyngeal lesions 80, 000 - 120, 000 U for extensive disease with duration of 3 or more days or edema of the neck (bulls neck) Administer IM for less severe disease Test all patients with a 1 :10 - 1 :100 dilution of DAT SC; if an immediate reaction occurs, administer epinephrine; hypersensitivity to horse serum is not a contraindication to antitoxin injection; desensitize subjects with increasing doses of diluted DAT Erythromycin & penicillin are both recommended for the treatment of diphtheria. Penicillin is recommended in household contacts who may not comply with the duration of erythromycin treatment. An increased incidence of pyloric stenosis is associated with administration of erythromycin to infants younger than 6 months. The treatment of endocarditis requires the addition of an amino glycoside.
Erythromycin

20 - 50 mg/kg/d IV divided bid; not to exceed 2 g/d; alternately, 40 - 50 mg/kg/d PO divided qid for 14 d
Penicillin G benzathine

Interferes with synthesis of cell wall mucopeptides during active multiplication, which results in bactericidal activity. Effective treatment for systemic diphtheria. < 30 lb : 60 mg PO (penicillin V) qid for 10 d; 300, 000 U/d IM (penicillin G benzathine) for 10 d 30 - 60 lb : 125 mg PO (penicillin V) qid for 10 d; 600, 000 U/d IM (penicillin G benzathine) for 10 d

Diphtheria antitoxin is derived from a horse serum, it neutralizes unbound exotoxin. It is to be administered as soon as diphtheria suspected. Administer immunization toxoid booster, as the antitoxin does not influence immunity.
Diphtheria antitoxin
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35
Measles

Measles is a highly communicable acute disease. It is also known as rubeola & is marked by prodromal fever,

cough, coryza, conjunctivitis & pathognomonic enanthem i.e. Koplik spots, followed by an erythematous maculopapular rash on the third to seventh day. Infection confers life - long immunity. Measles virus a negative - sense enveloped RNA virus, is a member of the Morbillivirus genus in the Paramyxoviridae family. A generalized immunosuppression that follows acute measles frequently predisposes patients to bacterial otitis media & bronchopneumonia. In approximately 0.1% of cases, measles causes acute encephalitis. Subacute sclerosing panencephalitis (SSPE) is a rare chronic degenerative disease that occurs several years after measles infection. Maternal antibodies play a significant role in protection against infection in infants younger than 1 year & may interfere with live - attenuated measles vaccination. A single dose of measles vaccine administered to a child older than 12 months induces protective immunity in 95% of recipients. Because measles virus is highly contagious, a 5% susceptible population is sufficient to sustain periodic outbreaks in otherwise highly vaccinated populations. Vitamin A supplementation during acute measles significantly reduces risks of morbidity & mortality. In temperate areas, the peak incidence of infection occurs during late winter & spring. Incubation period is 8 12 days. Measles virus is spread by direct contact via respiratory droplets or, less commonly, by airborne transmission. Initial infection & viral replication occur locally in tracheal & bronchial epithelial cells. After 2 - 4 days, measles virus infects local lymphatic tissues, perhaps carried by pulmonary macrophages.
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Following the amplification of measles virus in regional lymph nodes, a predominantly cell - associated viremia disseminates the virus to various organs prior to the appearance of rash. In individuals with deficiency in cellular immunity, measles virus causes progressive & often fatal giant cell pneumonia. Measles virus infection causes an immunosuppression marked by decreases in delayed - type hypersensitivity, interleukin 12 production & antigen - specific lymphoproliferative responses that persist for weeks to months after the acute infection. Immunosuppression may predispose individuals to severe bacterial infection, particularly bronchopneumonia, a major cause of measles - related mortality among younger children.

Mortality / Morbidity

Pathophysiology

Common infectious complications include otitis media, interstitial pneumonitis, bronchopneumonia, laryngotracheobronchitis (i.e. croup), exacerbation of tuberculosis, transient loss of hypersensitivity reaction to tuberculin skin test, encephalomyelitis & diarrhea. Rare complications include hemorrhagic measles, purpura fulminans, hepatitis, disseminated intravascular coagulation (DIC), and sub acute sclerosing panencephalitis (SSPE). Transient hepatitis may occur during an acute infection. SSPE, a degenerative CNS disease, can result from a persistent measles infection. SSPE is characterized by the onset of behavioral & intellectual deterioration & seizures years after an acute infection (the mean incubation period for SSPE is approximately 10.8 years). Measles is still a leading cause of death among children, despite the availability of an effective vaccine.
Age

Unvaccinated young children are at the highest risk. Age specific attack rates may be highest in susceptible infants younger than 12 months, school - aged children, or young adults, depending on local immunization practices & incidence of the disease.

Complications such as otitis media, bronchopneumonia, laryngotracheobronchitis (i.e. croup) & diarrhea are more common in young children.
History

The first sign of measles is usually a high fever that usually last 4 - 7 days. The prodromal phase is marked by malaise, fever, anorexia, and conjunctivitis, cough & coryza (the 3 Cs). Rash usually occurs, on average, 14 days after exposure & starts on the face & upper neck & spreads to extremities The entire course of uncomplicated measles, from late prodrome to resolution of fever & rash, is 7 - 10 days. Cough may be the final symptom to appear. Patients are contagious from 1 - 2 days before onset of symptoms. Healthy children are also contagious during the period from 3 - 5 days before the appearance of the rash to 4 days after the onset of rash. On the other hand, immunocompromised individuals can be contagious during the duration of the illness.

Desquamation & brown staining, which spares the palms & soles, may occur after one week. The rash may be absent in patients with underlying deficiencies in cellular immunity. Lymphoid involvement - Generalized lymphadenopathy, mild hepatomegaly & appendicitis may occur because of generalized involvement of lymphoid tissue.

Risk factors Risk factors for infection

Children with immunodeficiency due to HIV or acquired immunodeficiency syndrome (AIDS), leukemia, alkylating agents, or corticosteroid therapy, regardless of immunization status Travel to areas where measles is endemic or contact with travelers to endemic areas Infants who lose passive antibody prior to the age of routine immunization Malnutrition Underlying immunodeficiency Pregnancy Vitamin A deficiency Parvovirus B19 Infection Roseola Infantum Scarlet Fever Rubella Toxic Shock Syndrome

Risk factors for severe measles & its complications

Physical Fever - A temperature often exceeding 104F (40C) begins

with the prodrome & persists 7 - 10 days.

Enanthem - Koplik spots (i.e. bluish - gray specks or grains of

Differential Diagnoses

sand on a red base) appear on the buccal mucosa opposite the second molars near the end of the prodrome. It is generally seen 2 days prior to the appearance of the rash & lasts until 2 days after the rash appears. This enanthem begins to slough as the rash appears. Although this is the pathognomonic enanthem of measles, its absence does not exclude diagnosis.
Koplik spots in measles Rash - An erythematous & maculopapular rash that becomes

Dengue Drug Eruptions Enteroviral Infections Infectious Mononucleosis Kawasaki Disease Meningococcemia
Laboratory Studies

confluent begins on the face & then proceeds to the trunk, extremities, palms & soles; it lasts for about 5 days. Patients appear most ill during the first or second day of the rash.
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Diagnosis of measles is usually determined from the classic clinical picture. Laboratories can confirm measles by demonstrating more than a 4 - fold rise in immunoglobulin G (IgG) antibodies between acute & convalescent sera.

Patients with subacute sclerosing panencephalitis (SSPE) have unusually high titers of measles antibody in their serum & cerebrospinal fluid. The earliest confirmation of measles using IgG antibodies takes about 3 weeks from the onset of illness, a delay too long to permit implementation of effective control measures. Measles virus can be isolated from nasopharyngeal swabs. A leukopenia with a relative lymphocytosis occurs in the late stages of viremia. Elevated hepatic transaminase levels may be detected in patients with measles virus hepatitis.

o o

Other diagnostic tests

o o

Imaging Studies

Chest radiography is performed if bacterial pneumonia is suspected.

Other Tests

o o o
o

o o o

Lumbar puncture if encephalitis is suspected. Cerebrospinal fluid examination reveals the following : Increased protein Normal glucose Mild pleocytosis with a predominance of lymphocytes Treatment of measles is essentially supportive. Vitamin A supplements is associated with reduction in morbidity & mortality & is recommended in the following children : Those who live in developing countries or in areas of impoverishment in developed countries Children aged 6 - 24 months who are hospitalized for measles - related complications Those with immunodeficiency Those with evidence of an ophthalmologic complication due to vitamin A deficiency
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Children with malnutrition Children with impaired intestinal absorption To prevent or modify measles in exposed susceptible individuals, consider administering measles virus (MV) vaccine or human immunoglobulin (Ig). The morbidity rate is high in children younger than 1 year; therefore, Ig is recommended in these patients. The Measles virus vaccine is routinely administered as measles - mumps - rubella (MMR) in two doses. The first dose is given to healthy individuals at age 15 mts. The second dose is given upon school entry, usually at age 4 6 years. Ig is given to the following individuals : Those with immunocompromise Infants aged 6 months to 1 year Infants younger than 6 months who are born to mother without measles immunity Pregnant women

Vitamins

Medical Care

The World Health Organization (WHO) recommends vitamin A administration to all children with measles in communities where vitamin A deficiency is a recognized problem & where the measles virus (MV) - related mortality rate exceeds 1%. Two doses of vitamin A given 24 hours apart are recommended.
Vitamin A

o o o o

< 6 months : Not established 6 months to 1 year : 100, 000 IU PO as a single dose; repeat dose the next day & at 4 wk for ophthalmologic evidence of vitamin A deficiency > 1 year : 200, 000 IU PO as a single dose; repeat dose the next day & at 4 wk for ophthalmologic evidence of vitamin A deficiency
Immune globulin, intramuscular

Transient source of IgG. 0.25 mL/kg IM (0.5 mL/kg for patients with HIV); not to exceed

a cumulative dose of 15 mL; if dose exceeds 10 mL, divide dose into several muscle sites to reduce local pain

36

Meningitis is a clinical syndrome characterized by inflammation of the meninges. Encephalitis is defined as inflammation of the brain along with dysfunction of the brain. Encephalopathy only implies the dysfunction of the brain. Clinically, this medical condition manifests with meningeal symptoms (e.g. headache, nuchal rigidity & photophobia) & an increased number of white blood cells in the cerebrospinal fluid (CSF; pleocytosis). Depending on the duration of symptoms, meningitis may be classified as acute or chronic. Acute meningitis denotes the evolution of symptoms within hours to several days, while chronic meningitis has an onset & duration of weeks to months. The duration of symptoms of chronic meningitis is characteristically at least 4 weeks.

Causes

There are numerous infectious & noninfectious causes of meningitis. Noninfectious causes include medications (e.g. nonsteroidal anti - inflammatory drugs, antibiotics) & carcinomatosis. Depending on the specific bacterial cause, the syndrome may be called, for example, Streptococcus pneumoniae meningitis, meningococcal meningitis, or Haemophilus influenzae meningitis. Fungal & parasitic causes of meningitis are also termed according to their specific etiologic agent, such as cryptococcal meningitis, Histoplasma meningitis & amebic meningoencephalitis. Aseptic meningitis is defined as clinical & laboratory evidence of inflammation of the meninges (e.g., CSF pleocytosis & increased protein) without evidence of bacterial infection on Gram stain or
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culture. More than 80% of cases are caused by enteroviruses (i.e., coxsackievirus, enterovirus, echovirus, and, rarely, poliovirus). Aseptic meningitis is a broad term that denotes a non - pyogenic cellular response, which may be caused by many different etiologic agents. In many cases, a cause is not apparent after initial evaluation. Patients characteristically have an acute onset of meningeal symptoms, fever & cerebrospinal pleocytosis that is usually prominently lymphocytic. After an extensive workup, many of these cases are found to have a viral etiology & can then be reclassified as acute viral meningitis (e.g. enterovirus meningitis, herpes simplex virus [HSV] meningitis). While viruses cause most cases of aseptic meningitis, it can also be caused by bacterial, fungal, mycobacterial & parasitic agents. In general, the findings among neonates & young infants with meningitis are minimal & often subtle. Temperature instability (fever or hypothermia) occurs in approximately 60% of infected infants; increasing irritability is present in about 60%, poor feeding or vomiting in roughly 50% & seizures in about 40%. Lethargy, respiratory distress & diarrhea are frequent nonspecific manifestations of meningitis in this patient group. On physical examination, approximately 25% of newborns & young infants have a bulging fontanel & only 13% have nuchal rigidity. The diagnosis of meningitis cannot be excluded on the basis of the absence of these physical findings in infants.
Etiology of Meningitis Common - Enteroviruses

Less Common

Neisseria meningitidis Strep. Pneumoniae Group B streptococci Escherichia coli Haemophilus influenzae Listeria monocytogenes - Herpes simplex virus Klebsiella spp. (and other Enterobacteriaceae)

Mycobacterium tuberculosis Pseudomonas aeruginosa Staphylococcus aureus Rare - Cysticercosis Cryptococcus neoformans Lymphocytic choriomeningitis Mumps Syphilis Amoebae Any other cause of brain irritation is called as encephalopathy & can be seen with diseases such as hypertension (high BP), kidney failure (uremic encephalopathy), jaundice (hepatic encephalopathy), poisoning & heavy mental intoxication.
Diagnosis

Pathophysiology

Diagnosis of encephalitis is made by detecting cells in the cerebrospinal fluid. (Cerebrospinal fluid is the fluid present in the brain cavity). This cerebrospinal fluid also helps to detect the organisms causing the infection. MRI brain helps to determine which area of the brain is involved & look for complications such as brain abscess & hydrocephalus (increase in size of brain cavity due to increase pressure in the cerebrospinal fluid). EEG can help to determine Herpes virus infection. Other tests done are either CT scan or MRI of the brain. These are done to look for complications such as brain abscess, pus in the brain or look for increase in size of ventricles (hydrocephalus).
Complications

Rapidly progressive encephalitis can lead to more brain damage & death. Untreated bacterial, TB or fungal meningitis can lead to increase coma & death. Viral meningitis most often improves on its own. Meningitis can often be complicated with brain abscess or increase ventricle size. Common long term sequelae can occur in 30 percent of patients & include mental retardation, hearing loss, vision impairment, paralysis & epilepsy.
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Three major pathways exist by which an infectious agent (i.e. bacteria, virus, fungus & parasite) gains access to the central nervous system (CNS) & causes meningeal disease. Initially, the infectious agent colonizes or establishes a localized infection in the host. This may be in the form of colonization or infection of the skin, nasopharynx, respiratory tract, gastrointestinal tract, or genitourinary tract. From this site, the organism invades the submucosa by circumventing host defenses (e.g. physical barriers, local immunity, phagocytes/macrophages) & gains access to the CNS by 1) Invasion of the bloodstream (i.e. bacteremia, viremia, fungemia, parasitemia) & subsequent hematogenous seeding of the CNS, which is the most common mode of spread for most agents 2) A retrograde neuronal (i.e. olfactory & peripheral nerves) pathway or 3) Direct contiguous spread (i.e. sinusitis, otitis media, congenital malformations, trauma & direct inoculation during intracranial manipulation). Once inside the bloodstream, the infectious agent must escape immune surveillance (e.g. antibodies, complement - mediated bacterial killing & neutrophil phagocytosis). The ensuing cerebral edema (i.e. vasogenic, cytotoxic, interstitial) significantly contributes to intracranial hypertension & a consequent decrease in cerebral blood flow. Anaerobic metabolism ensues, which contributes to increased lactate concentration. Eventually, if this uncontrolled process is not modulated by effective treatment, transient neuronal dysfunction or permanent neuronal injury results. Another important component or complication of meningitis is the development of increased intracranial pressure (ICP). The pathophysiology of this complication is complex & may involve many proinflammatory molecules as well as mechanical

elements. Interstitial edema (secondary to obstruction of CSF flow, as in hydrocephalus), cytotoxic edema (swelling of cellular elements of the brain through the release of toxic factors from the bacteria & neutrophils) & vasogenic edema (increased BBB permeability) are all thought to play a role in the development of increased ICP.
Mortality / Morbidity

Animal contacts should be elicited. Patients with rabies could present atypically with aseptic meningitis & rabies should be suspected in a patient with a history of animal bite (e.g. dog, fox & bat). The presence of a ventriculoperitoneal shunt & a history of recent cranial surgery should be elicited. Signs of cerebral dysfunction are common, including confusion, irritability, delirium & coma. These are usually accompanied by fever & photophobia. Signs of meningeal irritation are observed in only approximately 50% of patients with bacterial meningitis & their absence certainly does not rule out meningitis. Kernig sign : In a supine patient, flex the hip to 90 while the knee is flexed at 90. An attempt to further extend the knee produces pain in the hamstrings & resistance to further extension. Brudzinski sign : Passively flex the neck while the patient is in a supine position with extremities extended. This maneuver produces flexion of the hips in patients with meningeal irritation. Nuchal rigidity : Resistance to passive flexion of the neck is also a sign. Exacerbation of existing headache by repeated horizontal movement of the head, at a rate of 2 - 3 times per second, may also suggest meningeal irritation. Cranial nerve palsies may be observed as a result of increased ICP or the presence of exudates encasing the nerve roots. Focal neurologic signs may develop as a result of ischemia from vascular inflammation & thrombosis. Seizures occur in approximately 30% of patients. Papilledema & other signs of increased ICP may be present. Coma, increased blood pressure with bradycardia & cranial nerve III palsy may be present.

Physical

Mortality from meningitis varies with the specific etiologic agent. The mortality rate for viral meningitis (without encephalitis) is less than 1%. In patients with deficient humoral immunity (e.g. agammaglobulinemia), enterovirus meningitis may have a fatal outcome. Bacterial meningitis was uniformly fatal before the antimicrobial era. With the advent of antimicrobial therapy, the overall mortality rate from bacterial meningitis has decreased but remains alarmingly high.
Age

Meningitis occurs in people of all age groups, but infants & young children & elderly individuals (> 60 y) are more predisposed to the infection.
History

o o

The classic presentation of meningitis includes fever, headache, neck stiffness, photophobia, nausea, vomiting & signs of cerebral dysfunction (e.g. lethargy, confusion & coma). These symptoms may develop later in the course of illness in some patients who may initially present with atypical symptoms such as leg pain & cold hands & feet. The triad of fever, nuchal rigidity & change in mental status is found in only two thirds of patients. The classic presentation of acute meningitis is the onset of symptoms within hours to a few days, compared to weeks for chronic meningitis.
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o o

o o o

The presence of papilledema also suggests a possible alternate diagnosis (e.g. brain abscess). Hepatosplenomegaly & lymphadenopathy suggest a systemic disease, including viral (e.g. mononucleosis like syndrome in EBV, CMV & HIV) & fungal (e.g. disseminated histoplasmosis) disease. The presence of a murmur suggests infective endocarditis with secondary bacterial seeding of the meninges. Evidence of parotitis is observed in some cases of mumps meningitis. The presence of a ventriculoperitoneal shunt or a cochlear implant may suggest a bacterial cause of meningitis. In contrast to bacterial meningitis, patients with aseptic meningitis syndrome usually appear clinically nontoxic with no vascular instability.

of the translocation of gut microflora with the Strongyloides stercoralis larva during hyperinfection syndrome).
Aseptic meningitis syndrome

Aseptic meningitis is the most common infectious syndrome affecting the CNS. Most episodes are caused by a viral pathogen, but they can also be caused by bacteria, fungi, or parasites.
Acute viral meningitis

Causes

S pneumoniae H influenzae Group A streptococci CSF shunts Coagulase - negative staphylococci S aureus Aerobic gram - negative bacilli Propionibacterium acnes Patients with hyposplenism, hypogammaglobulinemia, multiple myeloma, glucocorticoid treatment, defective complement (C1 - C4), diabetes mellitus, renal insufficiency, alcoholism, malnutrition & chronic liver disease are at increased risk. Other predisposing risk factors include 1) Neurosurgical procedures or intracranial manipulation; 2) Old age; 3) Immunosuppression; 4) High - grade gram - negative bacillary bacteremia; & 5) Disseminated strongyloidiasis, which has been reported as a classic cause of gram - negative bacillary bacteremia (as a result
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Basilar skull fracture

Viral meningitis comprises most aseptic meningitis syndromes. The viral agents for aseptic meningitis include the following : Enterovirus The non polio enteroviruses (NPEV) Herpes virus Varicella zoster virus (VZV), or HHV - 3 & CMV are causes of meningitis in immunocompromised hosts, especially patients with AIDS & transplant recipients. Human immunodeficiency virus o Aseptic meningitis syndrome may be the presenting symptom in a patient with acute HIV infection.
Chronic meningitis

Chronic meningitis is a constellation of signs & symptoms of meningeal irritation associated with CSF pleocytosis that persists for longer than 4 weeks. Chronic bacterial meningitis Tuberculous meningitis o M tuberculosis is an acid - fast bacillus that causes a broad range of clinical illnesses that can affect virtually any organ of the body. o Always consider tuberculous meningitis in the differential diagnoses of patients with aseptic meningitis or chronic meningitis syndromes. o Involvement of the CNS with tuberculous meningitis is usually caused by rupture of a tubercle into the subarachnoid space. o The presentation may be acute, but the classic presentation is subacute & spans weeks. Patients generally have a prodrome

of fever of varying degrees, malaise & intermittent headaches. Patients often develop central nerve palsies (III, IV, V, VI & VII), suggesting basilar meningeal involvement. Clinical staging of meningeal tuberculosis is based on neurologic status. Stage 1 shows no change in mental function with no deficits & no hydrocephalus. Stage 2 refers to a patient with confusion & evidence of neurologic deficit. Stage 3 refers to an individual with stupor & lethargy.

Differential Diagnosis

Brain Abscess Noninfectious meningitis, including medication - induced meningeal inflammation Meningeal carcinomatosis CNS vasculitis Stroke Encephalitis
Laboratory Studies

lymphocytic predominance may occur. Low CSF WBC count (< 20 cells/L) in the presence of a high bacterial load suggests a poor prognosis. The opening pressure (reference range is 80 - 200 mm H2O) may be elevated, suggesting some form of increased ICP from cerebral edema. The CSF glucose (reference range is 40 - 70 mg/dL) is less than 40 mg/dL in 60% of patients. Obtain a simultaneous blood glucose determination for comparison purposes. Some patients may have elevated blood sugar levels as a result of underlying diabetes mellitus & the predictive value of the CSF & blood sugar ratio may not be accurate in these circumstances. The CSF protein (reference range is 20 - 50 mg/dL) is usually elevated. CSF Gram stain permits rapid identification of the bacterial cause in 60 - 90% of patients with bacterial meningitis. The CSF picture of acute viral meningitis is different from the CSF picture of bacterial meningitis. The opening pressure is usually within the reference range. The CSF cell count is usually in the few hundreds (100 - 1000 cells/L) with a predominance of lymphocytes. Some cases of echovirus, mumps & HSV meningitis may produce a neutrophilic picture early in the course of disease. The CSF glucose level is usually within the reference range, but some cases of LCM, HSV, mumps & polio may cause low CSF glucose levels. CSF protein levels may be within the reference range but are usually elevated. Virus isolation from the CSF can be performed. Tuberculosis
meningitis

Acute viral meningitis

The cornerstone in the diagnosis of meningitis is examination of the CSF. In general, whenever the diagnosis of meningitis is strongly considered, promptly perform a lumbar puncture. Measure the opening pressure & send the fluid for cell count (and differential count), chemistry (i.e. CSF glucose & protein) & microbiology (i.e. Gram stain & cultures). CT scan of the brain may be performed prior to lumbar puncture in some patient groups with a higher risk of herniation. These groups include those with newly onset seizures, an immunocompromised state, signs suspicious for space occupying lesions (such as papilledema & focal neurologic signs) & moderate - to - severe impairment in consciousness. Examination of the CSF in patients with acute bacterial meningitis reveals the characteristic neutrophilic pleocytosis (usually hundreds to a few thousand, with > 80% PMN cells). In some cases of L monocytogenes meningitis (25 - 30%), a
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Bacterial meningitis

The CSF of patients with tuberculosis meningitis is characterized by a predominantly lymphocytic pleocytosis, usually in the hundreds.

The opening CSF pressure is usually elevated. A characteristic hypoglycorrhagia (glucose < 40 mg/dL) is present & the protein level is usually elevated, especially if a CSF block is present. The demonstration of the acid - fast bacilli (e.g. with auramine - rhodamine stain, Ziehl - Neelsen stain, Kinyoun stain) in the CSF is difficult & usually requires a large volume of CSF. Neuroimaging is indicated in patients with prolonged fever, focal neurologic symptoms & signs, evidence of increased ICP & suspected basilar fracture. It is also indicated for evaluation of the paranasal sinuses. These studies are helpful in the detection of CNS complications of bacterial meningitis, such as hydrocephalus, cerebral infarct, brain abscess, subdural empyema & venous sinus thrombosis.

Imaging Studies

adjunctive treatment of bacterial meningitis. If steroids are given, they should be administered prior to or during the administration of antimicrobial therapy. The use of steroids has been shown to improve the overall outcome of patients with certain types of bacterial meningitis, such as H influenzae, tuberculous & pneumococcal meningitis. Monitor for the occurrence of complications from the disease (e.g. hydrocephalus, seizures, hearing defects) & its treatment (e.g. drug toxicity, hypersensitivity). Recommended Empiric Antibiotics According to Predisposing Factors for patients with Suspected Bacterial Meningitis
Predisposing Feature Antibiotic (s)

Age 0 - 4 weeks Age 1 - 3 months Age 3 months to 50 years Older than 50 years

Procedures

Perform lumbar puncture promptly in all patients whenever a strong clinical suspicion for meningitis exists.
Medical Care

Bacterial meningitis is a neurological emergency that is associated with significant morbidity & mortality. The initiation of empiric antibacterial therapy is therefore essential for better outcome. The chosen antibiotic should attain adequate levels in the CSF. Achieving this usually depends on the drugs lipid solubility, its molecular size, its protein - binding capability & the state of inflammation at the meninges. The penicillins, certain cephalosporins (i.e., third - & fourth - generation cephalosporins), the carbapenems, fluoroquinolones & rifampin provide high CSF levels. The dose of the chosen antimicrobial agent should always be adjusted based on the renal & hepatic function of the patient. One of the major contributors to the morbidity associated with bacterial meningitis is the severity of inflammation. Therefore, pharmacologic interventions to reduce the degree of inflammation may improve outcome. Strongly consider the use of steroids as
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Impaired cellular immunity Neurosurgery, head trauma, or CSF shunt Specific Antibiotics & Duration of Therapy for Patients with Acute Bacterial Meningitis
Bacteria Antibiotic (s)

Ampicillin plus cefotaxime / an aminoglycoside Ampicillin plus cefotaxime plus vancomycin Ceftriaxone / cefotaxime plus vancomycin Ampicillin plus ceftriaxone / cefotaxime plus vancomycin Ampicillin plus ceftazidime plus vancomycin Vancomycin plus ceftazidime

Duration (Days)

S pneumoniae

H influenzae N meningitidis

Penicillin G 10 - 14 Ceftriaxone / cefotaxime Ceftriaxone / cefotaxime Ceftriaxone / cefotaxime plus vancomycin or rifampin Ampicillin 7 Ceftriaxone / cefotaxime Penicillin G / ampicillin 7

Ampicillin / penicillin G plus an aminoglycoside S agalactiae Penicillin G plus an aminoglycoside, if warranted Enterobacteriaceae Ceftriaxone / cefotaxime plus an aminoglycoside P aeruginosa Ceftazidime plus an aminoglycoside
Tuberculous meningitis

L monocytogenes

14 - 21 14 - 21

21 21

Complications may develop very rapidly. The symptoms often differ from those in adults & in any febrile illness malaria should be suspected if the child has been exposed. Because of plasmodial & mosquito resistance to drugs & insecticides, the danger of malaria has worsened & the disease is now a major global problem. Malaria is caused by Plasmodium species, which are protozoal blood parasites. The following 4 species can infect humans : P vivax (benign tertian) P falciparum (malignant tertian) P malariae (quartan malariae) P ovale (ovale malariae)

Causes

The treatment of tuberculosis meningitis should include antitubercular therapy for at least 12 months. At least 4 antitubercular drugs (INH, R, E, Z) should be included in the regime.
Surgical Care

In certain cases of increased ICP, repeated lumbar puncture or the insertion of a ventricular drain may be necessary to relieve the effects of increased ICP. Consultations with neurosurgical service may be needed when a skull fracture is suspected or an abscess formation is demonstrated.

Pathophysiology The female anopheles mosquito is infected with gametocytes of

Diet

No strict dietary restriction is necessary. To diminish the risks of aspiration, nothing by mouth is recommended for patients with altered levels of consciousness.

37
Malaria

Malaria (mal - foul, aria - air) is an ancient disease causing suffering to humanity. Children are the worst affected, especially children aged 6 months to 5 years. In parts of the world where malaria is endemic, it may cause as many as 10% of all deaths in children.
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plasmodium when it first sucks the infected blood from human body. Male anopheles does not suck blood but feeds on plant juices. After 7 20 days, sporozoites are formed in the mosquito. The bite of an infected mosquito introduces this asexual form of the parasite, the sporozoites, into the bloodstream of a healthy individual. Sporozoites enter the hepatocytes & form schizonts, which are also asexual forms. Schizonts undergo a process of maturation & multiplication known as pre erythrocytic or hepatic schizogony. In Plasmodium vivax & Plasmodium ovale infection, some sporozoites convert to dormant forms called hypnozoites, which can cause disease after months or years. Pre erythrocytic schizogony takes 6 - 16 days & results in the host cell bursting & releasing thousands of merozoites into the blood. Merozoites enter the erythrocytes & initiate another asexual reproductive cycle, known as erythrocytic schizogony. The parasite successively passes through the stages of

trophozoite & schizont, ultimately giving rise to several merozoites . Upon maturation of these merozoites, the

erythrocyte ruptures, releasing the merozoites & multiple antigenic & pyrogenic substances into the bloodstream. These merozoites again infect new erythrocytes. After a few cycles of this erythrocytic schizogony, some merozoites differentiate into the sexual forms : the male & female gametocytes. A mosquito that sucks this blood from a patient with gametocytemia acquires these sexual forms & plays host to the sexual stage of the plasmodial life cycle. Rupture of a large number of erythrocytes at the same time releases a large amount of pyrogens, which causes the paroxysms of malarial fever. The periodicity of malarial fever depends on the time required for the erythrocytic cycle & is definite for each species. Plasmodium malariae needs 72 hours for each cycle, leading to the name quartan malaria. The other 3 species each take 48 hours for one cycle & cause fever on alternate days (tertian malaria). However, this periodicity requires all the parasites to be developing & releasing simultaneously; if this synchronization is absent, periodicity is not observed. Most of the mortality of malaria is due to this complication of

Even without cerebral malaria, a child can experience prolonged, frequent convulsions, which can lead to prostration & death.
Age

Children of all ages living in non malarious areas are equally susceptible to malaria. In endemic areas, children younger than 5 years have repeated & often serious attacks of malaria. The survivors develop partial immunity. Thus, older children & adults often have asymptomatic parasitemia (i.e. presence of plasmodia in the bloodstream without clinical manifestations of malaria). Most deaths resulting from malaria occur in children younger than 5 years. History of blood transfusion, organ transplantation & (for newborns) malaria in the mother should be inquired. Young children manifest this disease in many different ways, but the classic picture of malaria, with periodic fever, shivering & sweating, is not observed. Malaria can mimic any febrile illness & should be suspected in any febrile child who has recently been in a malarious area. Older children may manifest the classic periodicity of fever with chills & shivering. After the mosquito bite, children are asymptomatic while the parasites complete the liver cycle & one erythrocytic cycle, which takes 8 - 18 days, depending on the species. Children then become restless, drowsy, apathetic & anorexic. Older children may report aching body, headache & nausea. Fever is usually continuous & may be very high (40C) from the first day. Many children have only flulike respiratory symptoms at presentation, with mild cough & cold. These symptoms abate in 1 - 2 days, with or without treatment. Vomiting is very common in children with malaria & may make oral therapy ineffective.

History

Cerebral malaria Plasmodium falciparum malaria, an acute illness that is mostly observed

in children aged 6 months to 3 years. Early diagnosis & prompt treatment with a drug to which the parasite is susceptible is important to save the life of the child.
Anemia

Anemia is so common in malaria that it is considered almost a part of the disease. The degree of anemia is related to destruction of erythrocytes which are infected by the parasites. Malarial anemia can be quite severe, sometimes causing death.
Repeated frequent seizures
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Mild diarrhea is often observed, with dark green mucoid stools. Occasionally, profuse diarrhea with dehydration & circulatory failure is observed. Seizures are common & may occur at the onset of the disease, even before high fever has set in. Parasitemia in neonates within 7 days of birth implies transplacental transmission. This congenital malaria is usually associated with placental parasitemia, which sometimes persists even after adequate treatment with antimalarial drugs. Babies have fever, are irritable, refuse feeds & often develop anemia, jaundice & hepatosplenomegaly. Children living in an area where malaria is endemic have repeated frequent infections & develop & maintain partial immunity. These children often develop only a low - grade fever, anemia, poor appetite & malaise. Tiredness, restlessness, cough & diarrhea are other symptoms that may occur. Complications include cerebral malaria, anaemia, severe jaundice, hypoglycemia & metabolic acidosis. Agitation & respiratory distress as a result of metabolic acidosis are ominous signs. Secondary bacterial sepsis is common & broad - spectrum antibiotics should be given to children with severe malaria. Renal failure & respiratory distress syndrome are rare in young children. Apart from other causes of fever, malaria is often misdiagnosed as meningitis, severe anaemia or hepatitis, with resultant delay in initiating therapy. Fever can be very high from the first day. In benign tertian malaria fever recurs every 48 hrs or on the 3rd day In malignant tertian malaria fever occurs on alternate days In quartan malaria, fever occurs every 72 hrs or 4th day.
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Temperatures of 40C & higher are often observed. Fever is usually continuous or irregular. Classic periodicity may be established after some days. The liver may be slightly tender. Splenomegaly takes many days, especially in the first attack in nonimmune children. In children from an endemic area, huge splenomegaly sometimes occurs. Prolonged malaria can cause anemia & malarial anemia causes significant mortality. With heavy parasitemia & large - scale destruction of erythrocytes, mild jaundice may occur. This jaundice subsides with the treatment of malaria. High fever, poor oral intake & vomiting all contribute to dehydration. Malaria can be transmitted through blood transfusion. The malaria transmitted is by the merozoites, which do not enter the liver cells. Because the liver stage is not present, curing the acute attack results in complete cure.
Risk factors include

Physical

Residence in, or travel through, a malarious area No previous exposure to malaria (hence no immunity) No chemoprophylaxis or improper chemoprophylaxis Pneumonia Salmonella Infection Sinusitis Tetanus Toxic Shock Syndrome Urinary Tract Infection Viral Hemorrhagic Fevers Yellow Fever Enteric fever Encephalitis Viral pneumonia

Differential diagnosis

Dengue Bacterial Endocarditis, Gastroenteritis Giardiasis Aseptic Meningitis, Bacterial Meningitis, Otitis Media Pharyngitis Plague Lobar pneumonia
Laboratory Studies

Demonstration of the parasite in a smear of the blood definitely establishes the presence of malaria. A negative finding on examination does not rule out malaria. Only 50% of children with malaria have positive smear findings, even on repeated examination. Asymptomatic parasitemia is common in children from an endemic area who have partial immunity to the disease. A positive smear for malaria parasite does not always confirm a diagnosis of malaria in these children. Both thick & thin films are essential. Thick smears are used for detection of the parasite & thin smear are used for identification of the individual type of parasite. DNA & RNA probes & polymerase chain reaction (PCR) have good sensitivity & specificity but require sophisticated expensive equipment. Lumbar puncture is indicated to rule out meningitis in cerebral malaria & febrile seizures with malaria. Severe P falciparum malaria is often associated with hypoglycemia. Lower blood glucose levels are associated with higher mortality rates.

Anticonvulsants may be needed to terminate seizures Infants & children under 5 years are at especially high risk of severe malaria & should not be taken into malarial areas unless this is essential. Children should be protected against mosquito bites at all times & mosquito nets used to cover bedding. It is advisable to keep babies under mosquito nets as much as possible between dusk & dawn. The inside of the house, especially the bedrooms, should be sprayed at dusk with an aerosol insecticide after closing the windows. Special insecticide mats, impregnated with insecticide, can be used. Skin repellents containing 20% DEET are effective against mosquito bites but are reported to be dangerous for use in children. Children with malaria who are fully conscious, who have low - to - moderate fever & who are maintaining their nutrition & hydration orally can be treated on an outpatient basis. Oral paracetamol is safe & effective for fever & should be used in doses of 10 mg/kg. This dose can be repeated 3 - 6 times a day, as required. If the child has hyperpyrexia, tepid sponging can rapidly bring the temperature down. Many children with malaria develop anemia. Because onset is gradual, the child withstands a low level of hemoglobin quite well & blood transfusions are rarely needed. Standard hematinic therapy is effective. If repeated vomiting has led to dehydration, the child needs appropriate parenteral fluids to correct it. Glucose - containing fluids help counter the hypoglycemia that sometimes accompanies severe malaria.

Prevention

Other Tests

Treatment

Procedures

Obtaining thick & thin blood films at the bedside is important. These films may have to be taken repeatedly for diagnosis. Earlobe or finger prick is used for older children; the great toe is used in infants.
Activity

Children should be allowed to decide their own activity levels. If the fever is intermittent, many children feel quite well between paroxysms of fever & come to no harm through activity.
Ancillary treatment in severe malaria

Watch for hypoglycemia Rehydration is important, but restricts fluids if unconscious

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Vomiting is common in malaria. An antiemetic such as domperidone can be used & antimalarials should be continued. Vomiting stops when the malaria is cured.

Indications for immediate hospitalization

Intractable vomiting Dehydration Seizures Altered consciousness or coma Repeated convulsions Difficulty in breathing or acidotic breathing Severe pallor (indicating severe anemia) Hypoglycemia Oliguria or anuria, signifying renal involvement Shock Bleeding diathesis In a child with malaria, impaired consciousness, respiratory distress, hypoglycemia & jaundice are risk factors for death. Such a child should be treated as an emergency. Chloroquine & proguanil can safely be given to babies & young children. Although chloroquine is secreted into the breast milk, the levels are not high enough to protect the breast - feeding infant. In fully breast - fed infants give half the recommended pediatric dose of chloroquine. Mefloquine is contraindicated in children weighing less than 15 kg. Doxycycline is contraindicated in children less than 8 years. Overdoses of chloroquine can have serious effects & all antimalarial drugs should be stored out of the reach of children in childproof containers. Blood schizonticides are the first - line drugs for the treatment of malaria & must be started as soon as the diagnosis is made or even suspected. They act on the asexual forms in the erythrocytes & interrupt clinical attacks. Delay in treatment of P falciparum malaria can lead to development of severe malaria, which has a poorer
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prognosis than uncomplicated malaria. Chloroquine, quinine, quinidine, mefloquine, halofantrine & artemisinin compounds are the rapidly acting drugs that can terminate an acute malaria attack. While chloroquine acts rapidly, resistance is widespread & an accurate travel history should be obtained before choosing the antimalarial drug. P vivax & P ovale have dormant stages (hypnozoites) in the liver & the treatment of an episode of malaria requires eradication of these forms also. The classic treatment is a 3 - day course of chloroquine, followed by a 14 - day course of primaquine.
Antimalarials

Blood schizonticides are the first - line drugs for the treatment of malaria.
Chloroquine

This drug is effective against the erythrocytic forms of the parasite & is the drug of choice for P vivax, P malariae & P ovale malaria, against which it is gametocidal as well.
Treatment

25 mg/kg (as base) PO over 3 d; 10 mg/kg initial dose (not to exceed 600 mg); followed by 3 doses of 5 mg/kg after 6, 24 & 48 h IM injections never used in children; may cause sudden death 5 mg/ kg IV diluted in IV fluid & infused over 6 h (0.8 mg/kg/h); can be administered q8h to complete course after 5 infusions or until patient can take PO medication to complete course
Quinine

A blood schizonticidal drug & still the DOC for severe & complicated malaria. It is gametocidal for P vivax & P malariae, but not for P falciparum. It is available as tabs containing 260 mg & as injections containing 300 mg/mL
Treatment

8.3 mg as base/kg PO tid for 7 d (equivalent to 10 mg as salt/ kg) Do not administer IM except as lifesaving measure in severe

malaria while awaiting transport to hospital with requisite facilities 15 - 20 mg/kg IV diluted in IV infusion fluid to 1 mg/mL; infuse over at least 4 h; followed by 10 mg/kg/dose q8 - 12h if continuation beyond 48 h is needed; reduce dose to 5 mg/kg q8h; switch to PO therapy as soon as possible
Quinidine

multidrug - resistant P falciparum < 40 kg : 8 mg/kg PO q6h for 3 doses; not to exceed 500 mg/dose; repeat after 1 wk > 40 kg : Administer as in adults Administer on empty stomach at least 1 h ac or 2 h pc
Mefloquine

A blood schizonticidal drug, it is as effective as quinine against blood schizonts but has significantly more cardiac toxicity. It is available as tabs of quinidine sulphate containing 200 mg. 25 - 30 mg as base/kg/d PO in divided doses for 7 d 15 mg/kg diluted in IV infusion fluid over at least 4h followed by 7.5 mg/kg/dose q8 - 12h; switch to PO therapy as soon as possible & complete 7 - d course
Pyrimethamine sulphadoxine

It is useful for the treatment of multidrug - resistant P falciparum infections. It is effective against blood schizonts but has no activity against hypnozoites & gametocytes. 15 - 25 mg as salt/kg PO as single dose
Artemether

Antifolate drug combination that is a slow - acting blood schizonticide, effective in some cases of chloroquine - resistant P falciparum malaria. < 2 months : Contraindicated > 2 months : 1.5 mg/kg (based on pyrimethamine component) PO pyrimethamine as a single dose
Primaquine

Effective against erythrocytic forms of all 4 human plasmodia but is used for multidrug - resistant P falciparum malaria. It has no action on hepatic forms or gametocytes. 4 mg/kg/d PO divided bid IM : Administer as in adults
Artesunate

The only drug in clinical use that destroys hypnozoites of both P vivax & P ovale & so is used for the radical cure of the relapsing malarias. It is also gametocidal against all 4 species of human plasmodia & is used to render patients noninfectious. Primaquine is also an effective & fairly safe drug for chemoprophylaxis For radical cure of P vivax & P ovale malarias : 0.3 mg/kg/d PO primaquine base for 14 d To render patient noninfectious : 0.3 mg/kg/d PO primaquine base for 5 d for P falciparum infection
Halofantrine

Effective against blood forms of all 4 types of human malaria parasites. Special usefulness is its action against multidrug - resistant P falciparum It has been found to be the fastest acting drug against blood forms of the malaria parasite & so the IV form is especially valuable in the management of severe & complicated malaria. 4 mg/kg PO on day 1, followed by 2 mg/kg/d for 3 - 5 d Alternatively, 3.2 mg/kg IV on day 1; may be divided bid; then 1.6 mg/kg IV qid for 4 d (total 9.6 mg/kg)
Clindamycin

An antibiotic that acts against P falciparum. It has been found to be very effective in combination with quinine, even against malaria acquired in areas where drug resistance is common. 5 - 10 mg/kg PO q12h for 3 - 7 d
Arthemether & lumefantrine

A rapid - acting drug against erythrocytic forms of malaria. Primarily used for treatment of acute attacks of malaria caused by
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Indicated for treatment of acute, uncomplicated P falciparum malaria, the most dangerous form of malaria. Contains fixed ratio of 20 mg of artemether & 120 mg of lumefantrine (1 : 6 parts).

Number of tab per dose by body weight

38
Mumps

Mumps is a benign viral infection of the salivary glands with systemic manifestations & complications. Mumps virus is a single - stranded RNA virus & a member of the family Paramyxoviridae, genus Paramyxovirus.

Pathophysiology

Symptoms in the history mostly consist of fever, headache & malaise. Within 24 hours, patients report an ear pain localized near the lobe of the ear & aggravated by a chewing movement of the jaw. The fever usually subsides after a variable period of as long as 1 week, well before the salivary gland edema disappears. Older children may describe a sensation of swelling at the angle of the jaw in the early stage, especially with a sour taste. After the prodromal period, one or both parotid glands begin to enlarge; 70 - 80% of cases are bilateral. Edema over the parotid gland typically occurs with non discrete borders, pain with pressure & obscured angle of the mandible. Parotitis : The classic illness of mumps consists of swelling of the parotid gland (i.e. parotitis, parotiditis). However, mumps is no longer the most common cause of parotitis. Systemic symptoms include low - grade fever, headache, malaise, anorexia & abdominal pain. Acid - containing foods may aggravate discomfort of the parotid gland. Ordinarily, the parotid gland is not palpable, but in patients with mumps, it rapidly progresses to maximum swelling over several days. Unilateral swelling usually occurs first, followed by bilateral parotid involvement. Occasionally, simultaneous involvement of both parotid glands occurs. Fever subsides within 1 week & disappears before swelling of the parotid gland resolves, which may require as long as 10 days. Other salivary glands may be involved, including both submaxillary glands & sublingual glands & orifices of the ducts may be erythematous & edematous. Orchitis : Approximately one third of postpubertal male patients develop unilateral orchitis. It usually follows parotitis but may

Mumps virus produces a generalized infection. After entry into the oropharynx, viral replication occurs, causing subsequent viremia & involving glands or nervous tissue. The virus may be isolated from saliva, blood, urine & cerebrospinal fluid (CSF). Affected glands show edema & lymphocyte infiltration.
Mortality / Morbidity

Physical

Approximately 10% of all infected patients develop a mild form of meningitis, which could be confused with bacterial meningitis. Encephalitis, transient myelitis, or polyneuritis is rare. Unilateral hearing loss is associated with mumps infection but is also rare. Orchitis occurs in 10 - 20% of patients; subsequent sterility is rare. Oophoritis is quite rare & is usually a benign inflammation of the ovaries. Other rare complications include myocarditis, nephritis, arthritis, thyroiditis, pancreatitis, thrombocytopenia purpura, mastitis & pneumonia. These usually resolve within 2 - 3 weeks without sequelae. The incubation period is 14 - 21 days & mumps is communicable from 6 days before to 9 days after facial swelling is apparent.

History

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precede parotitis or occur in the absence of parotitis. Meningoencephalitis - CNS involvement with mumps is not uncommon & it occurs more often as meningitis rather than true encephalitis. It may precede parotitis or appear in the absence of parotitis but usually occurs in the first week after parotitis. Headache, fever, nausea, vomiting & meningismus are common. Marked changes in sensorium & convulsions are not usual. Deafness : Neuritis of the auditory nerve may result in deafness. Sudden onset of tinnitus, ataxia & vomiting is followed by permanent deafness. Other neurologic complications include facial nerve neuritis & myelitis. Other complications : Less common complications include arthritis, myocarditis & hematologic complications.

CBC count reveals a normal or elevated WBC count with lymphocyte predominance. Viruria is common even in uncomplicated mumps.

Procedures

Lumbar puncture may be needed to obtain cell profile & culture information if meningoencephalitis is the prominent presentation.
Medical Care

Diet

Differential diagnosis

Human Immunodeficiency Virus Infection Coxsackievirus parotitis Influenza virus parotitis Parainfluenza virus parotitis Suppurative parotitis commonly caused by Staphylococcus aureus or other bacteria Adenitis Recurrent parotitis Calculus of Stensen duct Tumors of the parotid gland Upward pressure applied to the angle of the mandible produces tenderness with mumps (Hatchcocks sign); this maneuver produces no tenderness with adenitis.
Laboratory Studies

Conservative therapy is indicated in patients with mumps. Use of plenty of fluids is essential because adequate hydration & alimentation of patients is important. Foods & liquids that contain acid may cause swallowing difficulty as well as gastric irritation. Prescribe analgesics for severe headaches or discomfort due to parotitis. In orchitis, stronger analgesics may be needed. No antiviral agent is indicated for mumps, which is a self limited disease. A light diet with generous fluid intake is recommended. Avoiding acid - containing foods (e.g. tomato, vinegar containing food additives) & liquids (e.g. orange juice) are beneficial to reduce pain.

Activity

Bed rest is recommended for a faster recovery & is needed for patients with complicated cases.

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Attention Deficit Hyperactivity disorder (ADHD)

Diagnosis of mumps is clinical & laboratory tests are unnecessary. Serum amylase is elevated in mumps parotitis & pancreatitis. Serum lipase is elevated in pancreatitis.
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It refers to a persistent & pervasive disorder that initially manifests in childhood & is characterized by hyperactivity, impulsivity, and/or inattention. ADHD is usually noticed in children below 7 years of age. These symptoms can lead to difficulty in academic, emotional & social functioning.

This behavior makes it difficult for the child to adjust & adapt to the social environment in spite of having normal intelligence The term attention deficit is misleading. In general, the current predominating theories suggest that persons with attention deficit hyperactivity disorder (ADHD), attention deficit disorder (ADD), actually have difficulty regulating their attention; inhibiting their attention to non relevant stimuli, and/or focusing too intensely on specific stimuli to the exclusion of what is relevant. In one sense, rather than too little attention, many persons with ADHD (ADD) pay too much attention to too many things, leading them to have little focus. The diagnosis is established by satisfying specific criteria & may be associated with other neurological, significant behavioral, and/or developmental/learning disabilities. Therapy may consider the use of medication, behavioral therapy & adjustments in day - to - day lifestyle activities.

Three basic forms of ADHD (ADD) are

1) Attentional
Inattention

2) hyperactive/impulsive

3) Combined

Diagnostic Criteria

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All of the symptoms of inattention, hyperactivity & impulsivity must have persisted for at least six months to a degree that is maladaptive & inconsistent with the developmental level of the child.
The following features are usually seen in children with ADHD

The child often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities. The child often has difficulty sustaining attention in tasks or play activities. The child often does not seem to listen when spoken to directly. The child often does not follow through on instructions & fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions). The child often has difficulty organizing tasks & activities. The child often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as schoolwork or homework). The child often loses things necessary for tasks or activities (toys, school assignments, pencils, books, or tools). The child is often easily distracted by extraneous stimuli. The child is often forgetful in daily activities. The child often fidgets with his/her hands or feet or squirms in his/her seat. The child often leaves his/her seat in the classroom or in other situations in which remaining seated is expected. The child often runs about or climbs excessively in situations in which it is inappropriate. The child often has difficulty playing or engaging in leisure activities quietly. The child often talks excessively. The child often blurts out answers before questions have been completed. The child often has difficulty awaiting his/her turn.

Hyperactivity

The child may make repeated mistakes at school. The child may not be able to play the same game for a long time. The child cannot follow instructions. The child cannot organize work. The child is forgetful in daily activities & tends to lose things. The child is very fidgety. The child may walk away from class or from situations where the child is expected to remain seated. (e.g. climb tables, cupboards etc) They will be continuously talking. They tend to interrupt & disturb others.

Impulsivity

The child often interrupts or intrudes on others (for example, butts into conversations or games). Before labeling a child as ADHD, it is imperative to rule out physical causes of restlessness in children (commonest being worms). Also rule out epilepsy (an EEG may be recommended), psychosis, depression, anxiety etc. Many children with learning disabilities may suffer from short attention, as they may be depressed as they are unable to comprehend regular studies. Dreaming is a part of growing up & is considered normal. Abnormal day dreaming is when the dreams are so intense that they interfere with day to day activity. Criteria for diagnosis of ADHD requires that some hyperactive, impulsive, or inattention symptoms that cause present difficulties were present before 7 years of age & are present in two or more settings (at school [or work] or at home). The frontal cortex & the circuits linking them to the basal ganglia are critical for executive function and, therefore, to attention & exercising inhibition. Executive functions are major tasks of the frontal lobes. MRI in individuals with ADHD (ADD) also strongly supports weakened activity in the right inferior prefrontal cortex & left caudate during a task that involves timing of a motor response to a sensory cue. ADHD (ADD) is more frequently diagnosed in boys than in girls. Most estimates of the male - to - female ratio range between 3 :1 & 4 :1 in clinic populations. Past medical history Anticonvulsant agents Antihypertensive agents Caffeine - containing drugs Pseudoephedrine
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Ephedra

Screening for medical concerns that may have negative interactions with ADHD (ADD) medications (Drugs of concern are shown in parentheses.)

Pathophysiology

Major arterial disease (stimulants) Narrow - angle glaucoma (stimulants, imipramine, desipramine) Heart disease (clonidine, desipramine, guanfacine, imipramine, stimulants) Heart palpitations (stimulants) Hepatic disease (atomoxetine) Hypertension (stimulants, atomoxetine, bupropion) Orthostasis (atomoxetine, bupropion, stimulants) Pregnancy (all) Renal disease (bupropion, clonidine) Seizure disorder (bupropion, desipramine, imipramine) Urinary retention or hesitancy (atomoxetine, bupropion, stimulants) Anxiety disorders (generalized anxiety disorder [GAD], obsessive - compulsive disorder [OCD], panic disorder, social phobia) Bipolar disorder Communication disorder (receptive, expressive) Conduct disorder (oppositional defiant disorder in children) Depression Dissociative disorders Eating disorder Enuresis/encopresis Learning disability Pervasive developmental disorder including Asperger syndrome Posttraumatic stress disorder (PTSD) Psychotic disorders Sleep disorder (sleep apnea, restless leg syndrome, delayed sleep phase syndrome)

Consider screening patients for the following :

Sex

Screen for the following medications or supplements

Substance - related disorders Thought disorder Tourette syndrome or other tic disorders Somatic comorbidity (No somatic comorbidities are significantly associated with ADHD [ADD].) Family history : Inquire about a family history of ADHD Social history : Inquire about the following : Anger or rage reactions are prevalent. The child usually seems most awake in the late evening. Awakening the child for school causes major problems. Homework organization & completion are often a problem. High activity level is noted. Completion of multistep directions is difficult. Losing or forgetting material or conversations is observed. Report cards Reprimands or notes sent home Homework completion and/or turning homework in on time Extracurricular activities Drug abuse, alcohol abuse, or both Parent (s) with ADHD Physical abuse Sexual abuse Recent death of loved one or friend Severe chronic illness Severe financial problems

Tobacco (e.g. cigarettes, chewing tobacco, snuff)

Physical

Although a child or adolescent with ADHD (ADD) may exhibit few symptoms in a clinical setting, careful observation of behavior is important.
Vital signs

Home & family interactions consistent with ADHD

Height Weight Blood pressure Pulse

General appearance

o Fidgeting o Impulse control o State of arousal

Mental status examination

School performance

Affect Cognition Speech patterns Thought patterns

Family dysfunction

Causes

Abuse of substances by patient or his or her friends (if the patient is an adolescent)

The exact cause of ADHD is still not known, it is postulated that these children suffer from minimal brain damage either prenatal, at time of birth or even in the neonatal age group. Animal studies have demonstrated differences in the chemistry of brain transmitters involved with judgment, impulse control, alertness, planning & mental flexibility. A genetic predisposition has been demonstrated in (identical) twin & sibling studies.
Environmental causes

Alcohol Caffeine Other illicit drugs

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No environmental causes have been clearly identified. However, problems with pregnancy (including cigarette smoking during pregnancy) and/or delivery, head injuries, toxin exposure, heavy marijuana use beginning in early adolescence, marital or family

dysfunction & low social class have all been associated with ADHD.
Differential diagnosis

Anxiety Disorder : Generalized Anxiety Anxiety Disorder : Obsessive Compulsive Disorder Conduct Disorder Eating Disorder : Anorexia Eating Disorder : Bulimia Social phobia Psychotic disorders Post traumatic stress disorder (PTSD)
Laboratory Studies

Mood Disorder : Bipolar Disorder Mood Disorder : Depression

Teachers have an important function. Their periodic feedback about the childs school performance through the use of standardized scales, narrative descriptions & telephone follow - up is generally an indispensable component of ongoing care. Implementation of academic accommodations & adaptations is often necessary Behavioral modification & family therapy are usually necessary for optimal care. Refer parent (s) for evaluation of ADHD, if suspected.

Psychotherapeutics

Anxiety Disorder : Separation Anxiety & School Refusal Pervasive Developmental Disorder : Asperger Syndrome Sleep Disorder : Night Terrors Sleep Disorder : Nightmares Sleep Disorder : Problems Associated With Substance - related disorders

Activity

Regular physical activity is important in patients with some of the common coexistent conditions (e.g. depression, anxiety) & helps improve concentration. Therefore, physical activity is often an important component of therapy.
Medications

Workup in attention deficit hyperactivity disorder (ADHD) includes the following : Liver function tests Determination of CBC counts Drug screening
Imaging Studies

The 2 major components in the medical care of children with attention deficit
Categories of medications

Psychostimulants are effective in patients with ADHD. In addition, they have been available for many decades, allowing for a strong appreciation of their lack of major adverse effects when used at therapeutic doses.
Central alpha agonists

Evidence suggests that MRI & positron emission tomography (PET) may be useful as future diagnostic methods. Psychometric & educational testing is often important for the diagnosis of ADHD (ADD).

Central alpha agonists can be helpful in treating hyperactivity, tics, or delayed sleep onset.

40
Seizures / convulsions

Medical Care

The 2 major components in the medical care of children with attention deficit hyperactivity disorder (ADHD) are behavioral & pharmaceutical therapies.
School or education interventions
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Seizures are defined as an attack of recurrent, paroxysmal, involuntary, episodic clinical events associated with abnormal electrical activity from the neurons. A seizure is hypersynchronous neuronal activity. Hyper

synchronous, means unsynchronized. Seizures occur when the brain becomes irritable & abnormal electrical firings cause alterations in normal brain function. Usually, the patient becomes temporarily unresponsive & the exact location of the electrical short circuits will determine what abnormal physical findings are witnessed. Based on the type of behavior & brain activity, seizures are divided into 2 broad categories : 1) Generalized - Generalized seizures are produced by electrical impulses from throughout the entire brain 2) Partial (also called local or focal) - Partial seizures are produced (at least initially) by electrical impulses in a relatively small part of the brain. The part of the brain generating the seizures is sometimes called the focus. Absence seizures are a form of seizure in which a patient has a brief spell of staring blankly & becoming unresponsive for a few seconds to minutes.

1)

2)

3) 4)

The most common types of seizures are listed below Generalized Seizures Symptoms

(Produced by the entire brain)

1. Grand Mal / Generalized tonic - clonic 2. Absence (petit mal) 3. Myoclonic 4. Clonic 5. Tonic 6. Atonic Generalized seizures 1) Grand - mal seizure

Unconsciousness, convulsions, muscle rigidity Brief loss of consciousness Sporadic (isolated), jerking movements Repetitive, jerking movements Muscle stiffness, rigidity Loss of muscle tone

2)

In this type of seizure, the patient loses consciousness & usually collapses. Classically 4 stages are present namely 1) Aura 2) Tonic phase 3) Clonic phase 4) Post ictal phase
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3)

Aura - These are a type of warning symptoms the child experiences before the onset of convulsion. This typically include epigastric discomfort or pain, feeling of fear Tonic phase - In this phase there is loss of consciousness followed by generalized body stiffening (hyper tonicity) for 30 to 60 seconds. Skeletal muscles go into continuous spasm. Some children may emit a shrill cry due to spasm of laryngeal muscles, eyes may roll back & child may rapidly become cyanotic with apnea. There may be frothing from mouth. Urine or stool may be passed involuntarily. Clonic phase - There is violent jerking for 30 to 60 seconds, along with rhythmic clonic contractions & relaxations. Post ictal phase - After this the child goes into a deep sleep (after - seizure phase). It is a semicomatose condition which may remain for 30 min. to 2 hrs of duration. During grand mal seizures, injuries & accidents may occur, such as tongue biting & urinary incontinence. There may be truncal ataxia, hyperactive deep tendon reflexes, clonus & Babinski sign may be positive. The child has no or little recollection of the episode. Absence seizures (petit mal epilepsy) - In this type of seizures there is a short loss of consciousness (just a few seconds) with few or no symptoms. Sudden stopping of motor activity or speech may be observed. There is a blank facial expression with flickering of eyelids or a staring look. These seizures begin & end abruptly & may occur several times a day. Patients are usually not aware that they are having a seizure, except that they may be aware of losing time. This type of seizure is never associated with aura, loss of posture, no incontinence of urine or stool & no breathing difficulty. Most common age of occurrence is 6 - 8 yrs. Myoclonic seizures - It consists of repetitive jerks, usually on both sides of the body. Patients sometimes describe the jerks as brief electrical shocks. When violent, these seizures may

4) 5)

6)

result in loss of body tone with dropping/slumping forward or involuntarily throwing objects. Clonic seizures - These are repetitive, rhythmic jerks that involve both sides of the body at the same time. Tonic seizures - Are characterized by stiffening of the muscles. This causes all of muscles to suddenly contract, so the child falls down. Atonic seizures - It consists of a sudden & general loss of muscle tone, particularly in the arms & legs, which often results in a fall.
Symptoms

one part of the body & then involves entire body due to spread of electrical discharge to other parts of brain is called as partial seizure becoming secondarily generalized.
Pathophysiology

1) 2) 3) 4)
1)

Hereditary/genetic theory Biochemical theory Electro physical theory Neuro pathological theory
Hereditary theory

Partial Seizures (Produced by a small area of the brain)

Epilepsy can be familial There may be multifactorial/polygenic inheritance

2) Biochemical theory

Simple (awareness is retained)

Complex (Impairment of awareness)

Partial seizure with secondary generalization

a) Jerking, muscle rigidity, spasms, head - turning b) Unusual sensations affecting either the vision, hearing, smell taste / touch c) Memory / emotional disturbances Automatisms such as lip smacking, chewing, fidgeting, walking & other repetitive, involuntary but coordinated movements Symptoms that are initially associated with a preservation of consciousness that then evolves into a loss of consciousness & convulsions.

a) NA+ K+ ATPase theory NA+ K+ pump in resting phase the nerve cells are polarized due to differences in concentrations of ions across the cell membrane. This is called polarized state or RMP. At rest the charge on outside is + & inside is . When stimulated permeability of membrane to K & NA ion is changed. NA floods inside the neuron. This is called depolarization creating nerve impulse or action potential. In repolarization K ions flood out of the neurons & movement of these ions returns the membrane potential to its resting state. As the neuron returns to its original resting state the action of sodium potassium pump (Na - K ATPase) expels NA from the cell in exchange for K. In epileptic cortices (brain) levels of Na - K ATPase (enzyme)are low Na leaks into the neuronal cell &K remains outside RMP altered Depolarization
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Partial seizures

It often consists of change in one small thing, like a single motor disturbance, personality change & strange feelings. These are the only non generalized seizures. The electrical discharge begins in one part of the brain leading to involvement of only one side of body. They are also called focal seizures. If the patient remains conscious during the episode it is known as simple partial seizure & if becomes unconscious, it is known as complex partial seizure. A fit that starts in

Electrical discharge (until depolarization continues)

b) Neurotransmitter theory

Imbalance in the neurotransmitter concentrations is a major cause of seizures.2 main types of neurotransmitters are present excitatory (acetylcholine) & inhibitory (gamma amino butyric acid)
Formation of GABA

Glucose + protein = glutamine GABA (Cofactor pyridoxine B6) In newborns vit B6 deficiency is present. Hypoglycemia can lead to seizures.
c) Status epilepticus induced biochemical changes

Epilepsy. Head injury. Fever, causing febrile convulsions. Infection - especially meningitis & encephalitis. Metabolic problems such as hypoglycemia, hypoxia & hyponatremia, or thyroid storm. Increased ICP, commonly from brain haemorrhage or brain tumor. Drug abuse or medication withdrawal.

Investigations

In status epilepticus, there is continuous firing by the neurons which leads to increased motor action. This induces some biochemical changes like Hypoxia (due to high utilization & increased demand of O2) Hypoglycemia (due to high utilization & increased demand of glucose) Increased heat production due to increased motor activity (Vicious cycle) BMR Increased O2 & glucose demand
3) Electro physical theory

If a child suddenly has a seizure with no previous history, screening for intracranial causes with a head CT, ABG in order to rule out the metabolic causes. Next step is an EEG to scan the brains electrical patterns. Its most effective during a seizure, but some children with epilepsy will have abnormal patterns even when they are not in the middle of a seizure.
Management of acute episode

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It is characterized by recurrent, episodic, paroxysmal, involuntary clinical events in which clusters of nerve cells, or neurons, in the brain sometimes signal abnormally. In epilepsy, the normal pattern of neuronal activity becomes disturbed, causing strange sensations, emotions & behavior, or sometimes convulsions, muscle spasms & loss of consciousness. During a seizure, neurons may fire as many as 500 times a second, much faster than normal. For about 80 percent of those diagnosed with epilepsy, seizures can be controlled with modern medicines & surgical techniques. However, about 25 to 30 percent of people with epilepsy will continue to experience seizures even with the best available treatment. This is called as intractable epilepsy.

RMP altered neuronal cells excited neuronal firing Stimulus (decreased threshold) Causes seizures.
4) Neuro pathological theory

Pathological lesions of the brain like tumors, scars, infections, inflammation & vascular block can lead to convulsions.
Differential Diagnosis
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A single episode of seizure does not necessarily mean that a child has epilepsy. Only when a child experiences two or more seizures; he is considered to have epilepsy. Epilepsy is not contagious & is not caused by mental illness or mental retardation. Some children with mental retardation may experience seizures, but seizures do not necessarily mean the child has or will develop mental impairment. Many children with epilepsy have normal or above - average intelligence. Famous people who are known or rumored to have had epilepsy include the Russian writer Dostoyevsky, the philosopher Socrates, the military general Napoleon & the inventor of dynamite, Alfred Nobel, who established the Nobel Prize. Several Olympic medalists & other athletes also have had epilepsy. Prolonged refractory seizures can lead to brain damage. Some patients may develop poor memory due to epilepsy or it treatment. Excessive stress, worry & anxiety can also precipitate seizure. Sometimes epilepsy may be associated with a metabolic disorder in which case certain food items may have to be omitted. Lack of sleep may also precipitate seizures. Video games due to its flickering light & changing patterns of images can precipitate seizures. Certain drugs such as antidepressants, antibiotics, theophylline may provoke a seizure. Most children with well - controlled seizures & no additional handicap can attend a normal school. Extra curricular activity such as swimming, climbing & cycling on road should be avoided. Informing the schoolteacher about the childs disorder will aid in helping them to know what to expect when a child has a seizure & decide what to do. EEG may be abnormal in only about 60% of patients with epilepsy. Also, a small proportion of general population may have epileptiform abnormalities in EEG. EEG is useful in identifying type of epilepsy, detecting a structural brain abnormality; differentiate between true seizures
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& pseudoseizures.
Why do some patients continue to have seizures despite treatment? There could be several reasons

Inappropriate drug for a particular kind of seizure Incorrect dose of drug Irregular treatment Underlying condition is getting worse Patient does not have epilepsy at all Patient has true drug resistant seizure.

What are the side effects of anticonvulsant drugs?

Certain drugs such as phenobarbitone or phenytoin can cause memory disturbance. Some drugs may cause cosmetic side effects such as increase in gums or weight gain. 20% of patients have refractory seizures in spite of being on appropriate anti - seizure medication. These patients can be considered for epilepsy surgery. Some patients may respond to diet modification. Ketogenic diet (high fat diet) is used in small group of children with resistant seizures.
The following factors have a poor outcome

Epilepsy difficult to control More than one anti - seizure drug is required to control seizures Epilepsy is associated with structural brain damage Repeated episodes of prolonged seizures Associated mental retardation or cerebral palsy Seizures that start early (before 2 years of age). Epilepsy that starts between 5 & 13 years of age Epilepsy which is inherited Seizures that are easily controlled & require only drug to control it.

Following factors are associated with a good outcome

Measures to be taken at the time of seizure

Once a patient has seizures, clear the mouth to prevent difficulty in breathing. Put nothing in the mouth as it will not prevent biting but

may obstruct breathing. Turn the patient on the side so that tongue does not fall back & obstruct the airway. Do not try to hold the tongue. Call for a doctor & ambulance if seizures last more than 10 minutes.

resources, self - direction, functional academic skills, work, leisure, health & safety Onset before age 18 years

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The term locomotion means movement / travel. It may refer to Motion (physics) Animal locomotion - Terrestrial locomotion Travel Locomotion may refer to specific types of motion : Gait analysis walking running, including trotting jumping, including leaping gaits crawling climbing swimming flying

Causes

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Mental retardation is a state of developmental deficit, beginning in childhood, that results in significant limitation of intellect or cognition & poor adaptation to the demands of everyday life. It may be defined as a condition where a child is unable to learn & perform normally due to low intelligence. The Diagnostic & Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM - IV - TR) defines mental retardation as follows : Significantly subaverage intellectual functioning - An intelligence quotient (IQ) of approximately 70 or below Concurrent deficits or impairments in adaptive functioning in at least 2 of the following areas : communication, self - care, home living, social/interpersonal skills, use of community
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The causes of mental retardation can be grouped from most to least common as follows : Alterations in embryonic development, such as those caused by chromosomal abnormalities or fetal exposure to drugs or toxins Environmental deprivation & other mental disorders, such as autism Problems of pregnancy & the perinatal period, such as fetal malnutrition, hypoxia, infection, trauma, or prematurity Hereditary abnormalities, such as inborn errors of metabolism or chromosomal aberrations Medical conditions of infancy or childhood, such as central nervous system (CNS) infection or trauma, or lead poisoning. Physical causes are evident in most cases of moderate - to profound retardation. A disadvantaged environment is more likely in mild retardation. Many of the classification systems for mental retardation have been based on the timing of the insult to the CNS. The successive classification systems developed by the American Association on Mental Retardation also followed the timing approach.
Prenatal Causes - Genetic Disorders

Prenatal genetic disorders are characterized by changes in the genetic material, which may or may not have been inherited from the parents.
Chromosomal aberrations

Down syndrome Deletions A loss of part of a chromosome is called a deletion. The best known example is cri - du - chat syndrome, which is characterized by a high - pitched voice & is caused by a deletion in chromosome 5p3.

Malformation syndromes due to micro deletions Prader - Willi syndrome has an excessive appetite & indiscriminate eating habits, leading to obesity. Because this syndrome has no clear pathognomonic features, it may remain undiagnosed & such individuals might even be referred for psychiatric treatment because of an eating disorder.

Disorders with autosomal - dominant inheritance

Tuberous sclerosis is an example of the disorders in this group, which might be associated with mental retardation.
Disorders with autosomal - recessive inheritance

will be, as exemplified by congenital rubella. Rubella infection during the first month of pregnancy affects the organogenesis of 50% of embryos. Congenital cytomegalovirus infection may result in microcephaly, sensorineural hearing loss & psychomotor retardation Congenital toxoplasmosis may result in significant problems in approximately 20% of infected infants (e.g. hydrocephalus, microcephaly, psychomotor retardation, vision & hearing impairment) & in milder developmental problems later in life.
Toxic substances

Most metabolic disorders belong to this category. They are caused by single mutated genes that disturb the metabolism by deficient enzyme activity. Phenylketonuria (PKU) is the best known & most common of the metabolic disorders, with a prevalence of approximately 1 in 10, 000 live births. The enzymatic defect is diminished activity of phenylalanine hydroxylase, which leads to a high serum phenylalanine level, affecting, among other things, myelination of the CNS. Seizures & tremors are common, as are eczema & psychotic manifestations.
X - linked mental retardation

Fragile X syndrome is the most common inherited form of mental retardation and, after Down syndrome, the most common genetic form. It is X linked, with dominant inheritance & the penetrance is lower in females. Because of a constriction at the location Xq27.3, it appears as if the chromosome is fragile & a part of it is breaking off. Their developmental milestones, especially speech development, are delayed. After puberty, the characteristic phenotypical features may appear. They include an oblong face, prominent ears & jaw & macroorchidism.
Maternal infections

The most important of the teratogenic substances is ethanol, which is the cause of fetal alcohol syndrome (FAS). When used heavily during pregnancy; alcohol causes abnormalities in 3 main categories: 1) Dysmorphic features, which originate in the period of organogenesis; 2) Prenatal & postnatal growth retardation, including microcephaly; and 3) CNS dysfunction, including mild - to - moderate mental retardation, delay in motor development, hyperactivity & attention deficit. The severity of the symptoms is related to the amount of alcohol ingested.
Toxemia of pregnancy & placental insufficiency

Intrauterine growth retardation has many causes, the most important being maternal toxemia with its consequences, ending in insult to the CNS.
Perinatal Causes

This period refers to 1 week before birth to 4 weeks after birth.

Infections

Viral infections in the mother can interfere with organogenesis & the earlier in pregnancy they occur, the more severe their effect
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During the neonatal period, the most important infection, from the point of view of its developmental sequelae, is herpes simplex type 2. Neonatal bacterial infections might result in sepsis & meningitis, which, in turn, may cause hydrocephalus.
Delivery problems

During delivery, asphyxia is the most important factor causing an insult to the CNS. It leads to cell death, which might be demonstrated with neuroimaging techniques as leukomalacia. Premature infants & those with intrauterine growth retardation are at special risk for damage to the cortex or thalamus, which, in addition to affecting intelligence, causes various symptoms of cerebral palsy (CP) & seizure disorder, depending on the location of the pathological condition.
Other perinatal problems

Retinopathy of prematurity is seen frequently when the use of 100% oxygen in neonates is common, resulting in blindness. It is often associated with other CNS damage, mental retardation & other developmental problems. Infants with extremely low birth weight are at risk for intracranial hemorrhage & hypoglycemia resulting from a lack of hepatic glycogen storage.
Postnatal Causes Infections

The developmental level of a growing individual depends on the integrity of the CNS & on environmental & psychological factors. The importance of environmental stimulation for child development has been appreciated since research on children in institutions showed that development was severely affected in a depriving environment, even if adequate physical care was provided. Poverty predisposes the child to many developmental risks, such as teenage pregnancies, malnutrition, abuse, poor medical care & deprivation. Severe maternal mental illness is another risk factor. Children of mothers who have schizophrenia are at risk for the development of cognitive deficits, although these may not be secondary to maternal illness but may represent a genetically determined predisposition to schizophrenia.
Unknown causes

Despite detailed assessment, no cause can be identified in approximately 30% of cases of severe mental retardation & in 50% of cases of mild mental retardation.
Assessment

Bacterial & viral infections of the brain during childhood may cause meningitis & encephalitis & result in permanent damage.
Toxic substances

Lead poisoning is still an important cause of mental retardation. The most frequent source of lead is pica (i.e. ingestion of flaking, old, lead - based paint).
Other postnatal causes

Among childhood malignancies, brain tumors are second in frequency after leukemias. Of these, 70 - 80% are gliomas, symptoms of which depend mostly on location. Some are benign & treatable, but most have deleterious effects, resulting in various neuropsychiatric symptoms depending on their location & extent. Traffic accidents, drowning & other traumas are the most common causes of death during childhood. Even greater is the number of children who become disabled.
Psychosocial problems
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Mental retardation can be diagnosed by assessing the intelligent quotient (IQ) of the child. A child with IQ between 70 - 90 is said to have borderline mental retardation, IQ between 70 - 51 is mild mental retardation & IQ between 50 - 36 is moderate mental retardation. A child with IQ between 21 - 35 is severely retarded & those with IQ less than 20 have profound mental retardation. Children with severe & profound mental retardation have a significant amount of brain damage & may have associated blindness, deafness, seizures & other defects. They are fully dependent on others for care & survival. Children with moderate mental retardation can become partially independent with special training aimed at self - help skills. Children with mild mental retardation are able to talk, speak & carry out daily routine activities. They can be educated to a certain extent & can lead an independent life. Children with borderline mental retardation are usually low

achievers in school & by proper training can lead an independent normal life. Pseudo mental retardation - A child with a normal intelligence may appear to be mentally retarded due to other problems that prevent him/her to perform adequately. Deafness, blindness, emotional problems, speech problems, cerebral palsy & psychiatric problems may be associated factors leading to inadequate performing skills. Lowry & Sovner describe 4 functions of problem behavior that should be considered in any evaluation, as follows : Socio environmental control : Aggression & self - injurious behavior can be reinforced (i.e. removing a person from an unpleasant situation in response to such behavior will increase the probability that the person will react similarly in the future). Communication : Problem behaviors can be a nonverbal means of communicating a variety of messages (e.g. attention, discomfort, needs). Modulation of physical discomfort : Medical conditions, including adverse effects of medications, can cause physical discomfort, leading to aggression or self - injurious behavior. Modulation of emotional discomfort : Problem behaviors can occur as a state - dependent function of disorders such as major depression or bipolar disorder, manic phase.

ADHD should be differentiated from situation - specific inattentiveness, such as at school if the academic expectations are too high & adverse medication effects.
Mood disorders

Mood disorders, especially depressive disorders, are quite common in persons with mental retardation. Depression also may manifest as aggressive behavior. Environmental events, such as a precipitous move to a new setting or change in care provider, may trigger a depressive episode. Adverse effects of medications should be considered, for example, depression resulting from beta - blockers or agitation associated with akathisia from a neuroleptic drug.
Anxiety disorders

Verbal persons with mild mental retardation can report on subjective feelings of anxiety. In nonverbal persons, symptoms such as avoidance behaviors & agitation might suggest the diagnosis. The tendency toward anxiety & social avoidance also is a part of the behavioral phenotype of fragile X syndrome.
Posttraumatic stress disorder

Posttraumatic stress disorder in persons with mental retardation might be quite frequent & should be routinely considered in the differential diagnosis.
Obsessive - compulsive disorder

Specific Diagnosis of Common Comorbid Mental Disorders Pervasive developmental disorders

Most children with pervasive developmental disorders also have mental retardation. However, children with mental retardation alone do not have significant impairments in reciprocal social interaction & can engage in social communication, verbal or nonverbal (such as gestures & eye contact), appropriate to their developmental level.
Attention deficit hyperactivity disorder

The diagnosis of obsessive - compulsive disorder (OCD) may be difficult in nonverbal persons who cannot report on obsessional thoughts underlying their compulsions. Some repetitive behaviors, for example, hoarding objects, flicking lights on & off & tidying & arranging, all have been suggested as indications of OCD in persons with mental retardation.
Eating disorders

The diagnostic criteria for attention deficit hyperactivity disorder (ADHD) are based on observable behavior as reported by multiple informants & thus can be applied to nonverbal children.
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Anorexia & bulimia nervosa are relatively rare in the context of mental retardation, particularly moderate to severe mental retardation, but mental retardation is a predisposing factor for other eating disorders such as pica & rumination.

Treatment Planning & Stressors That May Trigger Problems

A complete evaluation & an individualized treatment plan require attention to the possible short - term & long - term stressors that may be triggering or exacerbating psychiatric disorders or behavioral problems in children with mental retardation. Stressors That May Trigger Behavioral Problems
Types of Stressor Examples

Transitional phases Change of residence, new school or work place, altered route to work. Development landmarks (e.g. going into puberty, achieving majority) Interpersonal loss Loss of parent, caregiver, friend, roommate. or rejection Breakup of romantic attachment. Being fired from a job or suspended from school Environmental Overcrowding, excessive noise, disorganization. Lack of satisfactory stimulation. Reduced privacy in congregate housing. School or work stress Parenting & social Lack of support from family, friends, or partner. support problems Destabilizing visits, phone calls, or letters. Neglect. Hostility. Physical or sexual abuse Illness / disability Chronic medical or psychiatric illness. Serious acute illness. Sensory defects. Difficulty with ambulation. Seizures Stigmatization Taunts, teasing, exclusion, because of physical/ being bullied / exploited. intellectual problems Frustration Due to inability to communicate needs & wishes. Due to lack of choices about residence, work situation, diet. Because of realization of deficits With increasing severity of mental retardation, the incidence of concomitant sensory & motor deficits increases. A greater degree of mental retardation suggests a greater amount
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of brain damage, reflected in a higher occurrence of impaired vision, hearing & speech & communication & a higher occurrence of seizure disorders. Management of mental retardation in a child requires a multi pronged approach. Each child needs individualized therapy & needs special education facilities, proper screening & treatment for vision & hearing problems & intervention by child psychologist, pediatrician, physiotherapist/occupational therapist & speech therapist to help him/ her achieve development to the best of his/her ability. The 3 behavioral interventions recommended by the expert consensus panel for most situations are as follows : Applied behavior analysis - Techniques that are based on the principles & methods of behavior analysis & are intended to build appropriate functional skills & reduce problem behavior include the following : o Behavior - accelerating procedures, such as contingent reward for specific behaviors that are incompatible with problem behavior o Behavior - decelerating techniques, such as contingent reward for specified time periods, during which the problem behavior did not occur; extinction; overcorrection; response cost; time out; contingent restraint o Behavioral parent & teacher/staff training to help them function as co - therapists and/or to avoid incidental reinforcement of the problem behavior Managing the environment - Reducing problem behaviors by rearranging physical and/or social conditions that seem to provoke them; examples include changes in activities (e.g. noise, temperature, lighting, crowding) and/or enrichment of environment through social or sensory stimulation Client and/or family education - Helping clients and/or families understand more about the behavioral psychiatric problems that may accompany mental retardation & how to manage them
Psychopharmacological Treatment

In many individuals with mental retardation, behavioral problems respond to psychosocial interventions. However, situations exist in which psychotropic medications can enhance a patients response to psychosocial treatment. Other clinical conditions require psychopharmacologic treatment at the outset.

Chronic suppurative OM (CSOM) is a chronic inflammation of the middle ear that persists at least 6 weeks & is associated with otorrhea through a perforated TM, an indwelling tympanostomy tube (TT), or a surgical myringotomy.
Pathophysiology

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Otitis media (OM) is the second most common disease of childhood, after upper respiratory infection (URI). OM is any inflammation of the middle ear without reference to etiology or pathogenesis. OM can be classified into many variants on the basis of etiology, duration, symptomatology & physical findings. Acute OM (AOM) implies rapid onset of disease associated with one or more of the following symptoms : Otalgia Fever Otorrhea Recent onset of anorexia Irritability Vomiting Diarrhea These symptoms are accompanied by abnormal Otoscopic findings of the tympanic membrane (TM), which may include the following : Opacity Bulging Erythema Middle ear effusion (MEE) Decreased mobility with pneumatic otoscopy OM with effusion (OME), formerly termed serous OM or secretory OM is MEE of any duration that lacks the associated signs & symptoms of infection (e.g. fever, otalgia, irritability). OME usually follows an episode of AOM.
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The most important factor in middle ear disease is eustachian tube (ET) dysfunction. In ET dysfunction (ETD), the mucosa at the pharyngeal end of the ET is part of the mucociliary system of the middle ear. Interference with this mucosa by edema, tumor, or negative intratympanic pressure facilitates direct extension of infectious processes from the nasopharynx to the middle ear, causing OM. Esophageal contents regurgitated into the nasopharynx & middle ear through the ET can create a direct mechanical disturbance of the middle ear mucosa & cause middle ear inflammation. In children, developmental alterations of the ET, an immature immune system & frequent infections of the upper respiratory mucosa all play major roles in AOM development. Certain viral infections cause abnormal host immune & inflammatory responses in the ET mucosa & subsequent microbial invasion of the middle ear. The host immune & inflammatory response to bacterial invasion of the middle ear produces fluid in the middle ear & the signs & symptoms of AOM.
Mortality / Morbidity

Morbidity from this disease remains significant, despite frequent use of systemic antibiotics to treat the illness & its complications. Intra temporal & intracranial complications of OM are the 2 major types.
Intra temporal complications

Hearing loss (conductive & sensorineural) TM perforation (acute & chronic) Chronic suppurative OM (with or without cholesteatoma) Cholesteatoma Tympanosclerosis Mastoiditis


Age

Petrositis Labyrinthitis Facial paralysis Cholesterol granuloma Infectious eczematoid dermatitis Meningitis Subdural empyema Brain abscess Extradural abscess Lateral sinus thrombosis Otitic hydrocephalus Peak prevalence of OM in both sexes occurs in children aged 6 - 18 months. Children who are diagnosed with AOM during the first year of life are much more likely to develop recurrent OM & chronic OME than children in whom the first middle ear infection occurs after age 1 year.

General

Intracranial complications

History of fever, although fevers greater than 40C are uncommon & may represent bacteremia or other complications. Irritability may be the sole early symptom in a young infant or toddler. A history of lethargy, although nonspecific, is a sensitive marker for sick children & should not be dismissed. Symptoms include anorexia, nausea, vomiting & diarrhea.

GI tract Exposure to environmental risk factors is another important aspect of the history & includes the following

Passive exposure to tobacco smoke Group daycare attendance Seasonality : AOM prevalence is much higher in winter & early spring than in summer & early fall. Supine bottle feeding (i.e. bottle propping)

Physical

History Suspect acute otitis media (AOM), with or without effusion, in children with a history of the following symptoms : Head & neck

Otalgia : Young children may exhibit signs of otalgia by pulling on the affected ear or ears or pulling on the hair. Otorrhea : Discharge may come from the middle ear through a recently perforated TM, through a preexisting TT, or through another perforation. For trauma patients, excluding a basilar skull fracture with associated cerebrospinal fluid (CSF) otorrhea is important. Headache Concurrent or recent URI symptoms (e.g. cough, rhinorrhea, sinus congestion)
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Pneumatic otoscopy remains the standard examination technique for patients with suspected OM. Proper pneumatic otoscopy technique is crucial to distinguish AOM from OME because recommended therapies for these entities are significantly different. Tympanometry, acoustic reflectometry & audiometry are important adjunctive techniques with which to evaluate patients with MEE.
Causes

A multitude of host, infectious, allergic & environmental factors contribute to OM development.

Host factors

Immune system : The immature immune systems of infants or the impaired immune systems of patients with congenital immune deficiencies, HIV infection, or diabetes may be involved in the development of OM.

Familial (genetic) predisposition : Although familial clustering of OM has been demonstrated, no specific genes have been linked to OM susceptibility. Mucins : The role of mucins in OME has been described. Mucins are responsible for gel - like properties of mucus secretions. The middle ear mucin gene expression is unique compared with the nasopharynx. Abnormalities of this gene expression, especially upregulation of MUC5B in the ear, may have a predominant role in OME. Anatomic abnormality : Children with anatomic abnormalities of the palate & associated musculature, especially the tensor veli palantini, exhibit marked ETD & have higher risk for OM. Specific anomalies that correlate with high prevalence of OM include cleft palate, Crouzon syndrome or Apert syndrome, Down syndrome & Treacher Collins syndrome. Physiologic dysfunction : Abnormalities in the physiologic function of the ET mucosa, including ciliary dysfunction & edema, increase the risk of bacterial invasion of the middle ear & the resultant OME. Vitamin A deficiency is associated with pediatric upper respiratory infections & AOM. Obesity has been linked to an increased incidence of OM, although the causal factor is unknown. Speculations include alteration of intrinsic cytokine profile, increased gastroesophageal reflux with alterations of the oral flora, and/ or fat accumulation; all of these have been linked with an increased incidence of OM.

Escherichia coli, Klebsiella species & Pseudomonas aeruginosa) play a much larger role in AOM. S pneumoniae & H influenzae are also the most common pathogens in this age group.
Viral pathogens

The viruses most commonly associated with AOM are respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses, rhinovirus & adenovirus. Human parechovirus 1 (HPeV1) infection is associated with OM & cough in pediatric patients.

Factors related to allergies

The relationship between allergies & OM remains unclear. In children younger than 4 years, the immune system is still developing & allergies are unlikely to play a role in recurrent AOM in this age group.
Brief list of evidence for & against the etiologic role of allergy in OM

Many patients with OM have concomitant allergic respiratory disease (e.g. allergic rhinitis, asthma). Many patients with OM have positive results to skin testing or radioallergosorbent testing (RAST). OM is most common in the winter & early spring, yet most major allergens (e.g. tree & grass pollens) peak in the late spring & early fall. Infant feeding methods The protective effects of breastfeeding for the first 3 - 6 months persist 4 - 12 months after breastfeeding ceases, possibly because delaying onset of the first OM episode reduces recurrence of OM in these children. Passive smoke exposure Group daycare attendance Daycare centers create close contact among many children, which increases the risks of respiratory infection,

Environmental factors

Infectious factors Bacterial pathogens

The most common bacterial pathogen in AOM is Streptococcus pneumoniae, followed by nontypeable Haemophilus influenzae & Moraxella catarrhalis. These 3 organisms are responsible for more than 95% of all AOM cases with a bacterial etiology. In infants younger than 6 weeks, gram - negative bacilli (e.g.
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nasopharyngeal colonization with pathogenic microbes & OM.

Socioeconomic factors

Imaging Studies

Socioeconomic status encompasses many independent factors that affect both the risk of OM & the likelihood that OM will be diagnosed. In general, lower socioeconomic status confers higher risk for environmental exposure to parental smoking, bottle - feeding, crowded group daycare, crowded living conditions & viruses & bacterial pathogens.
Differential Diagnoses

Imaging studies are not indicated in patients with OM unless intratemporal or intracranial complications are suspected. In patients in whom an OM complication is suspected, the imaging study of choice is a contrast - enhanced CT scan of the temporal bones. MRI is more helpful in depicting fluid collections, especially small middle ear collections. MRI is usually performed following CT if further information is needed for definitive diagnosis. Tympanometry may help with diagnosis in patients with OME. Some practitioners also use acoustic reflectometry to evaluate for MEE in patients with OM.

Allergic Rhinitis Apert Syndrome Bacteremia Cholesteatoma Cleft Lip & Palate Colic Diarrhea Down Syndrome Fever in the Toddler Fever in the Young Infant Fever Without a Focus Gastroenteritis Gastroesophageal Reflux Haemophilus Influenzae Infection Head Trauma Hearing Impairment Human Immunodeficiency Virus Infection
Laboratory Studies

Mastoiditis Meningitis, Bacterial Nasal Polyps Nasopharyngeal Cancer Otitis Externa Otosclerosis Parainfluenza Virus Infections Passive Smoking & Lung Disease Pharyngitis Pneumococcal Infections Primary Ciliary Dyskinesia Respiratory Syncytial Virus Infection Rhinovirus Infection Sinusitis

Other Tests

Medical Care Guidelines for medical management of AOM

To diagnose AOM, the clinician should confirm a history of acute onset, identify signs of MEE & evaluate for the presence of signs & symptoms of middle - ear inflammation. The management of AOM should include an assessment of pain. If pain is present, the clinician should recommend treatment to reduce pain. Acetaminophen & ibuprofen are first - line drugs for pain reduction. OM is one of the most common disorders in children & concern regarding antimicrobial resistance due to aggressive antibiotic use is growing. Observation without use of antibacterial agents in a child with uncomplicated AOM is an option for selected children based on diagnostic certainty, age, illness severity & assurance of follow - up.

OM is associated with multiple systemic diseases & congenital syndromes. AOM may be the first presenting illness in some of these diseases; therefore, order appropriate laboratory studies to confirm or exclude possible systemic or congenital diseases.
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Medical therapy

Most cases of OME occur after an episode of AOM & 67% of patients develop an MEE. The mean duration of the effusions is 23

days, but many persist much longer. Most cases of OME spontaneously resolve. Studies of the natural history of this disease report the following : The following are among the many strategies advocated for medical treatment in patients with OME : Antimicrobials Antihistamine - decongestants Intranasal & systemic steroids Nonsteroidal anti - inflammatory drugs (NSAIDs) Mucolytics Aggressive management of allergic symptoms
Surgical Care

Certain special patient populations, such as those with cleft palate, Down syndrome, or other craniofacial abnormalities, may require early surgical intervention to prevent OM.
Indications for tympanocentesis

o o o

OM in patients who have severe otalgia, who are seriously ill, or who appear toxic Unsatisfactory response to antimicrobial therapy OM in a newborn, sick neonate, or patient who is immunologically deficient, any of whom may harbor an unusual organism Initial surgery : Myringotomy & TT placement are the initial surgical techniques (withhold adenoidectomy unless the patient has a nasal obstruction). Tonsillectomy : Although it is not indicated for treatment of OM because it has not been shown to benefit ET function, tonsillectomy may be performed concurrently with surgery for OM if indications are present (e.g. frequently recurrent tonsillitis, pharyngeal obstruction).

Short stature is defined as length/height below 3rd percentile for age. Compared with a well - nourished, genetically relevant population, short stature is defined as a standing height more than 2 standard deviations (SDs) below the mean (or below the 2.5 percentile) for sex. Failure of physical, mental & sexual development is referred as infantilism. An adult male with height < 130 cm & female < 122 cm are called dwarf. Short stature can be promptly recognized only with accurate measurements of growth & critical analysis of growth data. Short stature, optimally defined relative to the genetic endowment of the individual, is recognized by comparing an individual childs height with that of a large population of a similar genetic background and, more particularly, using the mid - parental target height. Growth failure (GF) is often confused with short stature. By definition, GF is a pathologic state of abnormally low growth rate over time, whereas short stature is often a normal variant. Regardless of the genetic background, short stature may be a sign of a wide variety of pathologic conditions or inherited disorders. Skeletal maturation is typically determined by the bone age, which is assessed using anteroposterior radiography of the left hand & wrist.
Proportionate short stature

Causes A)

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Short stature
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Features - If upper limbs do not reach mid pelvis in infancy & upper thigh after infancy. Nutritional deprivation IUGR Endocrinal disorders Genetic disorders - down syndrome, Turners syndrome

Chronic diseases Emotional deprivation.

B) Disproportionate short stature (skeletal/bone dysplasias/genetic causes) Features short neck, small chest, protuberant abdomen.

a. With short limbs Achondroplasia Chondrodysplasia Hypochondroplasia Diastrophic dysplasia b. With short trunk Spondyloepiphyseal dysplasia Mucopolysaccharidosis Caries spine Hemi vertebrae
The causes of short stature can be divided into 3 broad categories

Short stature may be normal. Obtaining the family history of growth patterns & direct measurement of the parents is crucial to determine the genetic potential for growth in the child. Short stature can also be the sign of a wide variety of pathologic conditions or inherited disorders when it results from GF or premature closure of the epiphysial growth plates. Therefore, pathophysiology depends on the underlying cause.

Causes

1) 2) 3)

Chronic disease (including under nutrition genetic disorders), Familial (genetic) short stature & Constitutional delay of growth & development. Endocrine diseases are rare causes of short stature. The hallmark of endocrine disease is linear GF that occurs to a greater degree than weight loss. The hallmarks of familial short stature include bone age appropriate for chronologic age, normal growth velocity & predicted adult height appropriate to the familial pattern. By contrast, constitutional growth delay is characterized by delayed bone age, normal growth velocity & predicted adult height appropriate to the familial pattern. Patients with constitutional growth delay typically have a first - degree or second - degree relative with constitutional growth delay (e.g. menarche reached when older than 15 y, adult height attained in male relatives when older than 18 y).

The non endocrine causes of short stature can be divided into 3 major categories, as follows : Constitutional delay of growth & sexual development Birth length is normal & infants grow normally for few months. After that growth decreases. Adolescent growth spurt & sexual maturation is delayed. Finally achieved height is normal. Familial (genetic) short stature Parents or close relatives are short statured. Birth length near 3rd percentile. Age is normal. History & examination is normal. Chronic diseases of childhood : Among the chronic conditions, malnutrition remains the leading cause of short stature worldwide.
Genetic causes of short stature

Down syndrome (trisomy 21) Ullrich - Turner syndrome (45, XO) Ler - Weill dyschondrosteosis (SHOX gene)

Differential Diagnoses

Pathophysiology
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Achondrogenesis Hypercalcemia Achondroplasia Hypercalciuria Acidosis Respiratory & Metabolic Hypogonadism Hyponatremia Adrenal Hypoplasia Hypopituitarism Adrenal Insufficiency Hypothyroidism

Alkalosis Metabolic & Respiratory Irritable Bowel Syndrome Laron Syndrome Anemia, Chronic Late Effects of Childhood Cancer & Treatment Bartter Syndrome Malabsorption Syndromes Bone Marrow Transplantation Marasmus Congenital Adrenal Hyperplasia Constitutional Growth Delay Microphallus Noonan Syndrome Crohn Disease Panhypopituitarism Cryptosporidiosis Pellagra Cystic Fibrosis Rickets Diarrhea Short Bowel Syndrome Disorders of Bone Mineralization Silver - Russell Syndrome Down Syndrome Sprue Eating Disorder : Thyroiditis Anorexia & bulimia Turner Syndrome Failure to Thrive Ulcerative Colitis Glycogen - Storage Disease Type I Williams Syndrome Growth Failure Growth Hormone Deficiency Human Immunodeficiency Virus Infection
Causes of normal variant short stature (also called familial short stature) Genetic (known defect)

Renal

Insulin receptor gene mutations (leprechaunism) Silver - Russell syndrome Shwachman - Diamond syndrome CF Severe asthma Chronic obstructive pulmonary disease Restrictive lung disease Hypoxemia Congestive heart failure Low cardiac output states Precocious puberty Chronic renal insufficiency Renal failure Renal tubular acidosis Chronic neglect Starvation

Genetic (unknown defect)

Pulmonic

Cardiac

Sex

Psychosocial dwarfism

Down syndrome (trisomy 21) Silver - Russell syndrome Hypochondroplasia Turner syndrome Growth hormone (GH) receptor gene mutations (Laron syndrome) GHRH gene mutations GH gene mutations
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Boys who are short are more likely to come to medical attention than girls who are short. Boys do appear more likely to have idiopathic GHD or constitutional delay of growth & development. Ullrich Turner syndrome (i.e. TS) affects only females. The evaluation of a short female, or a female with primary amenorrhea, mandates a karyotype to exclude this disorder.
History

Key data to obtain for the evaluation of short stature include the childs weight & length at birth; prior growth pattern; & the final (or current) heights & weights of parents, siblings & grandparents. Whenever possible, obtain the original birth records to

o
o o o

document length, weight & fronto - occipital circumference at birth. Assessing the heights of both parents is absolutely essential. Generally, men over report their height & women underreport their weight. Ideally, measure each parents height in the clinic for optimal calculation of the mid - parental target height, according to one of several formulas, among which the author prefers the following : Target height in cm for a girl = [mothers height in cm + (fathers height in cm - 13)]/2 Target height in cm for a boy = [(mothers height in cm + 13) + fathers height in cm)]/2 Document pubertal timing in first - degree relatives. At a minimum, determine the age at onset of menarche for the childs mother & the age of adult height attainment for the father. Most parents can usually recall these 2 milestones, which have proven reliable predictors of pubertal timing & tempo in parent - child pair studies of puberty. Review of symptoms by organ system provides additional clues to the etiology underlying short stature. GI Diarrhea, flatulence, or borborygmi (frequent, discomforting, or even audible peristalsis) suggest malabsorption. Vomiting can suggest an eating disorder or a CNS disorder (e.g. dysgerminoma). Consider dietary intake & composition. In particular, ask about intake of carbonated beverages, juices & other casual intake. Pain or abdominal discomfort suggests inflammatory bowel diseases. Cardiac disease : Signs include peripheral edema, murmurs & cyanosis. Chronic infections : Poor wound healing & opportunistic
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o o

o o o
o

infections are signs of potential immune deficiency. Pulmonary Sleep apnea can be a cryptic cause of short stature. Other chronic diseases that may result in short stature include severe asthma associated with chronic steroid use & cystic fibrosis (CF). Neurologic Visual field deficits often herald pituitary neoplasms. Vomiting, early morning nausea, polyuria, or polydipsia is often associated with masses of the CNS. Renal Polyuria & polydipsia are important symptoms of hypothalamic & pituitary disorders. Chronic renal disease is a common cause of growth failure (GF). Social Participation in sports that require weight control (e.g. wrestling, crew & gymnastics) may be associated with anorexia nervosa or bulimia induced by the patient, peers, or coaches. The growth pattern with adequate nutrition in a loving environment over time is critical to distinguish pathologic GF from normal variant short stature in such patients.

Physical Clinical evaluation 1) US : LS - birth 1.7 : 1

3yrs 1.3 : 1 7yrs 1 : 1 Then LS increases slightly US (1 : 1.1)

2) 3) High velocity

< 4cm/yr between 5 - 12 yrs indicates pathological short stature.

Mid parental height

Rough estimation of projected adult ht. Boys = fathers ht. + (mothers ht +13cm)/ 2


4)

Girls = mothers ht. + (fathers ht 13cm)/2

X - ray for bone age

5)

o o

At birth & neonates X - ray knees (for epiphysis at lower end of femur & upper of tibia) Up to 8 yrs X - wrists (carpal bones appearance & their number) Later X - ray elbows etc. SMR SMR should be assessed using tanners method. Measure standing height in triplicate using a calibrated wall mounted stadiometer. In infants, length is determined in triplicate using a tabletop recumbent infantometer. The mean value of the triplicate data serves as the true measurement. In children who cannot completely stand or recline (e.g. those with spina bifida, those with contractures), arm span provides a reliable alternative for longitudinal assessment of long bone growth. Documenting growth velocity over time complements the initial height assessment. Calculate growth velocity as the change in standing height over at least 6 months (in children) or in length over at least 4 months (in infants). Poor linear growth is defined as linear growth velocity more than 2 SDs below the mean for gender, genetic composition & chronologic age. Weigh all patients. In infants, determine the fronto - occipital circumference. In patients in whom short - limb dwarfism is suspected, the sitting height can be obtained by measuring the upper body segment, or crown to pelvis, as the child sits upright on a platform - mounted stadiometer (or on the floor with a wall mounted stadiometer). Alternatively, the lower segment can be determined by
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o o

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o

measuring from the superior midline brim of the symphysis pubis to the floor, with the child standing (feet placed together). The upper - to - lower segment ratio (US/LS) should be close to 1. Both the arm span & US/LS ratio can be informative regarding the cause of short stature. Patients with short - limb dwarfism usually have an US/LS ratio that remains above 1.3. Newborns typically display a ratio of 1.7, which gradually drops to approximately 1 during prepubertal growth & remains close to 1 in adulthood. The ratio is more than 1 in children with shortened limbs, as it is in individuals with hypochondroplasia or achondroplasia. Palpate for thyroid enlargement & firmness, which can be associated with Hashimoto thyroiditis, the most common cause of acquired hypothyroidism. Test visual fields for signs of pituitary & hypothalamic tumors, initially by gross confrontation. Inspect fourth metacarpals, which are shortened in persons with pseudohypoparathyroidism, Ullrich - Turner syndrome & Albright hereditary osteodystrophy. Inspect mucous membranes for ulcerative stomatitis, typical of Crohn disease & various trace mineral & vitamin deficiencies. Pretibial ulcerations are also observed in persons with Crohn disease & ulcerative colitis. Rectal tags & clubbing are also typical in individuals with Crohn disease. Arm span also reveals a decrement in growth, which is otherwise indiscernible in a child with spinal deformation (e.g. myelomeningocele). Carefully examine the midface. A single, central, maxillary incisor reflects a defect in midline facial development. Similarly, a bifid uvula suggests the possibility of a

submandibular cleft palate, which may be palpable, yet not visible on inspection. Associated anomalies of midline structures, such as the pituitary gland, are common in patients with major midline facial anomalies. Growth hormone deficiency (GHD) or panhypopituitarism should be considered as a cause of short stature in such patients.
Types

damaged child. Proportionate dwarf upper segment : lower segment is normal for given age. e.g. hypopitutarism. Disproportionate US : LS is abnormal for given age. e.g. hypothyroidism, skeletal dysplasias.
Waterlow classification of stunting

Short stature Normal variant Pathological Familial short stature Constitutional delay in growth Proportionate short stature disproportionate short stature Pre - natal Post - natal onset rickets, all skeletal dysplasias. IUGR Chromosomal disorders Dysmorphic disorders Malnutrition GI disorders Celiac disease Chronic diarrhea Cardiac diseases CCF Cyanotic heart diseases Respiratory diseases asthma cystic fibrosis Renal disorders CRF RTA Chronic anaemia haemolytic anaemia Chronic infections chronic TB Endocrinal disorders hypopitutarism, DM Cushing syndrome, hypothyroidism, hypogonadism Psychosocial short stature maternal deprivation, brain
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Height for age normal 90 - 95% 85 - 90% < 85%

Laboratory Studies

grade 1st degree 2nd degree 3rd degree

> 95%

Laboratory studies used to assess the major causes of short stature in children include the following : Measurement of serum levels of insulin like growth factor - I (IGF - I), formerly named somatomedin C & IGF binding protein - 3 (IGFBP - 3) These are useful tests for growth hormone deficiency (GHD), except in pubertal patients & those with history of a brain tumor. Measuring serum levels of GH Beyond the first months of life, endogenous GH is secreted in a pulsatile fashion. These intermittent peaks are greatest after exercise, after meals (as blood glucose levels decrease) & during deep sleep. Therefore, measuring a single random serum GH value is of no use in the evaluation of the short child. Beyond the neonatal period, values obtained during the daytime are unlikely to be detectable. Although a random serum GH value of more than 10 mg/dL generally excludes GHD, a random low serum GH concentration does not confirm the diagnosis of GHD.
Other useful tests include the following

CBC count for hematologic disease Wintrobe sedimentation rate for inflammatory bowel disease

Antiendomysial immunoglobulin A (IgA) & immunoglobulin G (IgG), transglutaminase IgG & antigliadin IgG titers for sprue (gluten enteropathy) (Antiendomysial IgA titers are more sensitive & IgG titers are more specific.) Serum total thyroxine (total T4) & thyrotropin (TSH) levels to test for hypothyroidism Sweat chloride testing to exclude cystic fibrosis (CF) : Consider this test in patients who are short & have a history of meconium ileus or pulmonary symptoms. Serum transferrin & prealbumin concentrations for under nutrition

individuals) Lack of key design elements for a proper clinical trial (e.g. placebo controls, double blinding, randomization) Inadequate follow - up study to final adult height

Surgical Care

Surgical care depends on the underlying cause of short stature. Brain tumors that cause hyposomatotropism may require neurosurgical intervention, depending on the tumor type & location (see Hyposomatotropism). Limb - lengthening procedures have been performed but carry enormous morbidity & mortality risks & are not recommended.
Diet

Imaging Studies

Perform anteroposterior radiography of left hand & wrist to assess bone age. Chondrodysplasia of the distal radial epiphysis (Madelung deformity) suggests Ler - Weill dyschondrosteosis. Perform renal & cardiac ultrasonography in all patients with Ullrich - Turner syndrome. The most commonly associated anomalies include horseshoe kidney & bicuspid aortic valve.
Treatment

Optimize nutrition in patients with GI disease. Obtain psychologic or psychiatric consultation for patients with eating disorders. Forced energy intake in children with normal variant short stature has not been demonstrated to improve short - term growth or final adult height.
Activity

1) 2) 3) 4)

Treatment of cause infections, hypothyroidism, D. M. Treatment of malnutrition vitamins, haematinics, deworming In case of GH deficiency 0.1U/kg/day At pubertal age administration of sex steroids.

Do not restrict activity in children with normal variant short stature.

Medication

Medication administered depends on the etiology of the short stature.

Growth Hormone

Medical Care

Medical care depends on the etiology of the short stature. Recombinant human growth hormone (rhGH) administration has not been proven to remarkably improve final adult height in children with normal variant short stature. Nine inconclusive clinical studies that focused on this particular issue have been published to date. Published studies were flawed because of the following : Selection bias due to high drop - out rates from treatment regimens (presumably due, in part, to the parents or health care providers dissatisfaction with results of therapy in these
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These agents improve symptoms associated with growth hormone deficiency (GHD).
Somatropin

hGH produced via recombinant DNA technology in Escherichia coli; widely available since 1985. Regimens vary according to product & the indication The following doses of recombinant human somatotropin analogs have proven effective Non - Laron IGFD : 0.05 mg/kg/d SC hs for prepubertal

children, 0.1 mg/kg/d SC for pubertal females; 0.2 mg/kg/d SC for pubertal males TS or chronic renal insufficiency : 0.08 mg/kg/d SC h s Prader - Willi syndrome : 0.05 mg/kg/d SC
Mecasermin

(0.1 mg) is to be given intramuscularly to all babies. Breast - feeding should be given within half an hour in babies born vaginally & within 4 hours of a caesarean section.
Delivery room care

1)

Recombinant human insulin like growth factor - 1 (rhIGF - 1) indicated for long - term treatment of GF in children with severe primary IGFD (primary IGFD defined as basal serum IGF - I level & height SD scores < - 3, normal or elevated serum GH level). IGF - I is essential for normal growth of childrens bones, cartilage & organs by stimulating uptake of glucose, fatty acids & amino acids into tissues. IGF - I is the principal hormone for linear growth & directly mediates GH actions. Primary IGFD is characterized by absent IGF I production despite normal or elevated GH release. < 2 years : Not established > 2 years : 0.04 - 0.08 mg/kg SC bid initially with meal or snack; if tolerated after 1 wk, may increase by 0.04 mg/kg/ dose, not to exceed 0.12 mg/kg bid Individualize dose & adjust downward if hypoglycemia occurs

2)

3)

4)

46 55 56
Neonatal resuscitation Care of baby at time of delivery

As soon as the baby is born & is breathing effectively, the baby should be dried & covered in pre - warmed clothes & placed in a warmer. The eyes should be cleaned with sterile saline (use fresh cotton swab for each eye) & if required eye drops can be installed to prevent conjunctivitis. The umbilical cord should be tied by a disposable umbilical clamp with the clamp applied at least 2 to 3 cm away from the base of the cord. The base & tip of the cut umbilical cord should be cleaned with spirit or alcohol. Vitamin K injection
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All equipments must be set up & checked before delivery. The infant who fails to breathe spontaneously at birth should be placed under a radiant warmer, dried & positioned to open the airway. The mouth & nares should be suctioned & gentle stimulation should be provided. The mouth should be suctioned first to prevent aspiration into the lungs. Prolonged or overly vigorous suctioning may lead to bradycardia & should be avoided unless moderate - to - thick meconium is present in the airway. The infant born with primary apnea is most likely to respond to the stimulation of drying & gentle tapping of the soles of the feet. The infant who fails to respond rapidly to these measures is experiencing secondary apnea & requires positive pressure bag ventilation with oxygen. Adequate ventilation is assessed by looking for chest wall excursions & listening for air exchange. The heart rate should be assessed while positive pressure ventilation is being applied. If the heart rate does not increase rapidly after ventilation, chest compressions must be started by an assistant. If the infant fails to respond to these measures, intubation & medications are necessary. Epinephrine can be administered via the endotracheal tube. Apgar scores are used to assess the status of the infant at 0, 1, 5 & 10 min following delivery. Ensure breathing has been established adequately. Head low position Cleaning clean hands, surface, clean razor, clean cord clamp, clean cord stump. Mouth should be cleaned with sterile gauze or suctioned with suction bulb or mucous trap, first from the nose.

Routine delivery room care of the newborn

1) 2) 3) 4)

 5)

Mucus trap is called De Lee catheter. Stomach wash with NS is indicated in following conditions Babies born by LSCS. Severely asphyxiated babies Polyhydramnios Meconium stained liquor SFD babies Single umbilical artery Maintenance of body temperature Body temperature in newborn is unstable Body surface area is 3 times more than adult. Infants body heat falls by app.0.3 c/min. of skin & 0.1 c/min of Hence newborns are more prone to develop hypothermia.

The quantity of brown fat is directly related to weight of baby. Brown fat is important source of heat production in newborns. Ways of heat loss in newborns 1) Evaporation Evaporation of amniotic fluid from skin 2) Conduction Contact with cold objects e.g. cloths, trays 3) Convection hot air surrounding the baby is replaced by cold air 4) Radiation heat is radiated from the body of the baby Vitamin K is given to the infant by intramuscular injection to prevent hemorrhagic disease of the newborn. Vitamin K injection is given in the dose of 1 mg =0.1 ml intramuscular in the anterolateral aspect of the thigh.
Ocular prophylaxis

core.
Maintenance of body temperature

Newborn babies are prone to getting low body temperature & hence bath is usually given after a day or 2 after delivery to prevent hypothermia. The room in which the baby is to be kept should be warm & baby should be effectively covered with caps & socks to prevent hypothermia. Oil massage provides insulation against heat loss & is useful in maintaining body temperature. Exposure of the baby to direct sunlight during hot summer months should be avoided. 36.5 37 c Normal temp. < 36.5 to 36 c Cold stress Moderate hypothermia < 36 to 32 c < 32 c Severe hypothermia LBW baby has decreased thermal insulation due to reduced subcutaneous fat. Brown fat is site for heat production. It is located around adrenal glands, kidney & nape of the neck, interscapular & axillary regions. Blood flowing from brown fat becomes warm & with circulation transfers heat to other parts of body. This is known as non shivering thermogenesis.
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Clean eyes with saline water & cotton immediately after the birth of the baby. Erythromycin ophthalmic ointment should be installed for prevention against gonorrheal & chlamydial infection & is administered after birth.
Skin care & cord care

Bath should be given with lukewarm water & undedicated soap. Dip baths should be avoided till the cord has fallen. Scalp, neck, armpits & diaper area should be cleaned properly. The umbilical cord should be checked after 2 to 4 hours of clamping. Ethyl Alcohol should be applied at the tip & around the base of the umbilical stump everyday to prevent colonization. The cord should be kept dry. The cord usually falls off in 5 to 10 days. If the cord has not fallen off even after 14 days, then consult your doctor. Any discharge or redness from the cord may suggest infection & a doctor should be consulted.
Umbilical cord care

Umbilical cord should be inspected for number of arteries & veins. Meconium stained cord is one of the sign of (MAS) meconium aspiration syndrome. Umbilical cord should be clamped preferably with a cord clamp.

Local application of triple dye or bacitracin ointment should be applied.

Vaccination

during the first week of life may range from 94 to 175 beats per minute.
Assessment of the adequacy of fetal growth 1) Gestational age assessment - The gestational age of the newborn

BCG vaccine should be given to the newborn before discharge from the hospital along with zero dose of OPV.
Hepatitis B prophylaxis

infant is assessed with the help of Ballard score of neuromuscular & physical maturity.
2) Premature infants

If the mother is hepatitis B surface antigen - positive (HBsAg), or if she has active hepatitis B, the infant should be given an IM injection of hepatitis B immune globulin & a course of three injections of hepatitis B vaccine (before hospital discharge & at 1 & 6 months of age).
Physical examination of the newborn General examination

a)

b)

The examiner should assess whether the infant appears to be sick or well. Look for any generalized edema which may be due to prematurity, hypoprotenemia, hydrops fetalis Following observations should be assessed Temperature, Respiratory distress, Pallor, cyanosis, An unusual cry may indicate sepsis, hypothyroidism, a congenital anomaly of the larynx, or a chromosomal abnormality.
Vital signs

A preterm infant is defined as an infant of less than 37 weeks gestation & a post term infant is defined as being of greater than 42 weeks gestation. Preterm infants may develop respiratory distress syndrome, apnea, bradycardia & retinopathy of prematurity. Respiratory distress syndrome is recognized by tachypnea, grunting, retractions, an elevated oxygen requirement & a roentgenographic picture of poor inflation & a fine homogeneous ground - glass appearance. Height, weight, head circumference, chest circumference & mid arm circumference should be measured. A low - birth weight infant is defined as any neonate with a birth weight < 2, 500 g. Height, weight & head circumference should be plotted as a function of gestational age on an intrauterine growth chart. Factors that may result in an infant who is small for gestational age include chromosomal & other dysmorphic syndromes, congenital infections, maternal hypertension & smoking, uterine anomalies & multiple gestations. The small - for - gestational age infant is at greater risk for cold stress, hypoglycemia, hypocalcemia & polycythemia. The differential diagnosis for the large - for - gestational age infant includes maternal diabetes & maternal obesity. The large - for - gestational age infant is at risk for shoulder dystocia, birth trauma & hypoglycemia.

Measurements & growth charts

1)

The normal temperature of the newborn is 36.5 to 37.0 degrees

vital sign/age Temp. Pulse Respiratory rate Blood pressure

2)

newborn 1mth to 1 year

a)

36.5 to 130 to 37 0C 150 110 to 130

appro.40 30 to 40

70/45 70 - 75 / 45 - 50 3) 4)

Chest wall excursions should be observed & the respiratory rate

b)

determined. The normal neonatal respiratory rate is 40 to 60 breaths per minute. Auscultation of breath & heart sounds. The normal heart rate
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Examination of organ systems & regions

1) a)

Head, face & neck The head circumference is measured & plotted & the scalp, b)

fontanelles & sutures are examined. Moulding i.e. overriding of the parietal bones over the frontal & occipital bones may be present. Bruising & hematomas of the scalp should be noted. Cephalohematoma, caput succedaneum, vacuum caput should be looked for. b) Dysmorphic facial features that suggest a chromosomal anomaly include mid facial hypoplasia, small eyes, or low - set ears. Neck should be examined to rule out goiter, cystic hygroma & sternocleidomastoid tumor. c) The eyes should be examined with an ophthalmoscope to document a red reflex. The absence of a clear red reflex is indicative of a retinoblastoma, cataract, or glaucoma. d) The lips, mouth & palate are inspected & palpated for clefts. Nares patency can be documented by closing the mouth & occluding one nostril at a time while observing air flow through the opposite nostril. Epstein pearls are present on the hard palate
2) Abdomen & gastrointestinal system

torticollis, Down syndrome & breech presentation. The female to male ratio is 7 :1. Ultrasonography is used to evaluate suspected hip dysplasia. Fracture of the clavicle occurs in 0.2 - 3.5% of vaginal deliveries. Physical findings include local swelling & crepitations & an asymmetric Moro reflex. Treatment consists of making a sling by pinning the shirt sleeve of the involved side to the opposite side of the shirt.
Hypoglycemia

Common neonatal problems A)

1)

2)
B)

Hypoglycemia is common in premature infants, infants who are small for gestational age, infants of diabetic mothers & infants who have experienced perinatal asphyxia. Hypoglycemia is defined as a blood glucose of < 40 - 45 mg/ dL. Hypoglycemic infants require early feedings or IV glucose. Anemia during the newborn period may be caused by hemolytic & congenital anemias, fetal - to - maternal hemorrhage, placental abruption & occult hemorrhage.
Bilirubin metabolism

Visual inspection of the abdomen should be done to assess symmetry & distension. Generally liver is 2 cm palpable below the right coastal margin. Distended abdomen may be observed in obstruction, perforation, meconium ileus. Abdominal palpation for masses, hepatosplenomegaly, or renal masses is completed & the anus should be visually inspected.
3) Genitourinary system

C)

1)

2)

The genitalia are examined for ambiguous genitalia, which requires immediate endocrinologic & urologic consultation. In case of male babies examine the genitalias for undescended testis, retractile testis.
4) a) Musculoskeletal system Hip examination may detect developmental dysplasia &

Hyperbilirubinemia occurs frequently in the normal newborn because of increased production & decreased elimination of this breakdown product of heme. Initial workup for neonatal hyperbilirubinemia includes measurements of total & direct bilirubin levels, hematocrit, Coombs test & testing of urine for reducing substances to exclude galactosemia. High levels of bilirubin can cause an acute encephalopathy (i.e. kernicterus).

Jaundice

congenital dislocation of the hips (CDH). Risk factors for hip dysplasia include a family history, foot deformities, congenital
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About 60 to 70 percent of newborn babies develop jaundice on 2nd or 3rd day of life which disappears within 7 - 10 days. This is a normal physiological process & is known as physiological jaundice & no treatment is required. If the jaundice starts within first 24 hours of life or is very deep or it persists beyond 2 weeks of life, then other

causes of neonatal jaundice should be promptly investigated

D) Gastrointestinal problems

Urine output

1)

2)

Ninety - six percent of full - term newborns pass a meconium stool before 24 hours of age. A delayed or absent passage of meconium may be caused by meconium plug syndrome, Hirschsprung disease, meconium ileus (cystic fibrosis), or imperforate anus. Bilious vomiting in the newborn is always abnormal & usually is caused by an intestinal obstruction. Vomiting in the newborn also may be caused by inborn errors of metabolism & congenital adrenal hyperplasia.
Urinary problems

Most newborns pass urine within 48 hours of birth. If the baby has not passed urine within 48 hours, a urinary tract problem should be ruled out. A normal baby passes about 5 - 10 times urine per day. Babies usually cry on passing urine due to wet nappies. If the urine stream in narrow, or there is excessive straining on passing urine or there is dribbling at the end, a bladder or kidney problem should be ruled out.
Fever

E)

Ninety - nine percent of normal full - term infants will urinate by 24 hours. If urination has not occurred within 24 hours, renal ultrasonography should be done & an intravenous fluid challenge may be given.
Feeding problems Regurgitation of milk

During the summer months, some babies may develop transitory fever during the second or third day of life. The child is however active & keen to feed. This is known as Dehydration fever & is a transient condition & due to excessive environment temperature. Ensuring proper feeds & hydration leads to disappearance of the fever.
Excessive crying in newborns

Most newborns bring up some amount of milk soon after feeding. It is a normal phenomenon. A baby swallows air while sucking (aerophagy) & as air is burped out part of the milk also comes out along with the air. Hence burping the baby by holding upright on the shoulder for 5 to 10 minutes after the feed relieves the gas & regurgitation.
Stools

Most babies cry when they are either hungry or having discomfort such as wet nappies or soiled stools. Sometimes insect bites, nose block & some trivial trauma may be reasons for cry. An infant with colic may have gaseous distension of abdomen & usually feels comfortable when placed in prone position which facilitates expulsion of gas. Presence of inconsolable crying or a high - pitched cry may suggest infection & should be referred to the doctor immediately.
Sleep variation

During the first two to three days, the baby passes black, tarry stools (meconium) which are followed by greenish stools (transitional stools) for next 1 or 2 days & then regular semisolid sticky golden yellow stools. Most babies pass 4 to 8 stools in a day (some babies pass stools after each feed) whereas some babies pass stools once in 2 - 3 days. This can be a normal pattern. When the baby is being breastfed & is not receiving any other top feeding, it is unlikely to develop diarrhea due to infection.
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During first few days of life, most babies keep their eyes closed & go to sleep after taking only a few sucks at the breast. Also most newborns sleep during the day & are awake & playful during the night. This is probably because in the mothers womb, during the daytime, the baby is rocked in the amniotic water & sleeps & when the mother is resting at night, the baby is active & playful. Babies tend to fall into a set sleep pattern in 4 - 6 weeks.

57
Modifications present in fetal circulation 1) 2 umbilical arteries carry deoxygenated blood from the foetus

to the placenta.
2) 3) 1 umbilical vein carries oxygenated blood from placenta to the

foetus.
Ductus venosus is the continuation of umbilical vein which

4)

5)

connects directly to the inferior vena cava thus most of the blood bypasses the liver which is non functional in the foetus. Ductus arteriosus connects the pulmonary artery to the descending aorta thus shunting the blood in systemic circulation as foetal lungs are nonfunctional. (Its oxygen requirement is fulfilled through mothers blood via the placenta), Foramen ovale is a valve like opening which allows the blood flow from right to left atrium thus allowing very small amount of blood to flow towards the fetal lungs.

In utero

Because the lungs are inactive in the foetus the heart does not pump much blood towards it. For this reason the foramen ovale, links the right atrium to the left, allowing blood to pump through from right to left. Since small amount of blood comes back from the lungs, pressure in the left atrium is low & is high in the right atrium. This high pressure keeps the valve adherent so that it can cover the open hole. Fetal pulmonary vascular resistance (PVR) is high & the fetal systemic vascular resistance (SVR) is low. Within minutes of delivery, the newborns pulmonary vascular resistance decreases.
Pulmonary blood flow

& then passes into the inferior vena cava. Relatively little mixing of the blood occurs in the inferior vena cava from these 2 sites. The more highly oxygenated blood, which has bypassed the liver, streams into the inferior vena cava to pass preferentially through the patent foramen ovale into the left atrium. The desaturated blood returning from the liver & lower body streams into the inferior vena cava to the right atrium. In the right atrium, it mixes with blood returning from the coronary sinus & superior vena cava & flows into the right ventricle. The more highly oxygenated blood that crosses the foramen ovale mixes with the small amount of pulmonary venous return & then crosses the mitral valve into the left ventricle. The output from the left ventricle passes into the ascending aorta to the heart, brain, head & upper torso. The less saturated blood from the right ventricle passes into the pulmonary arteries. Because the pulmonary vessels are constricted & highly resistant to flow, only about 12% of this blood enters the lungs. The remainder of the blood takes the path of least resistance through the patent ductus arteriosus into the descending aorta. Approximately one third of this blood is carried to the trunk, abdomen & lower extremities, with the remainder entering the umbilical artery where it is returned to the placenta for reoxygenation.
Changes after birth

The umbilical vein carries the oxygenated blood from the placenta to the fetus. Blood flow in the umbilical vein divides at the porta hepatis, with 50 - 60% of the blood passing directly to the inferior vena cava via the ductus venosus & the remainder of the blood passing into the portal circulation. This portal blood flow perfuses the liver
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As soon as the baby takes its first breaths, the lungs inflate which increases the pulmonary blood flow. This results in more blood coming back from the lungs, thus raising left atrial pressure. This causes the flap over foramen ovale to shut down & prevent the blood flow between atria. As the pulmonary circulation starts the blood oxygen levels are increased, which causes the constriction of the ductus arteriosus. Cutting of the cord stops the placental circulation & thus the umbilical vein, ductus venosus & umbilical arteries are collapsed. This creates the same heart circulation as is seen in adults. Over the next few hours/days, the ductus arteriosis closes up too, creating the standard circulation.

When it goes wrong

Again, the ductus arteriosis can fail to close. This is more serious however, since the higher pressure in the aorta than the pulmonary artery means that there is a left - to - right shunt & the child can suffer from labored breathing & failure to thrive. There is also high possibility of congestive heart failure if the patent duct is not closed surgically. In some congenital conditions such as Transposition of the Great Arteries, or Tetralogy of Fallot, the abnormalities are such that if the normal closure of these ducts takes place, the baby suddenly has great difficulties, or dies. In these cases it is referred to as a duct dependant circulation; if the ducts close, the blood no longer circulates to all parts of the body adequately.

58

Preterm birth refers to the birth of a baby with less than 37

weeks from the last day of the menstrual period.

Premature birth, commonly used as a synonym for preterm birth,

Preterm IUGR Symmetrical Asymmetrical Mixed In the normal human fetus, several organ systems mature between 34 & 37 weeks & the fetus reaches adequate maturity by the end of this period. One of the main organs greatly affected by premature birth is the lungs. The lungs are one of the last organs to develop in the womb; because of this, premature babies typically spend the first days/weeks of their life on a ventilator. Therefore, a significant overlap exists between preterm birth & prematurity : generally, preterm babies are premature & term babies are mature. Prematurity can be reduced to a small extent by using drugs to accelerate maturation of the fetus & to a greater extent by preventing preterm birth.

refers to the birth of a baby before its organs mature enough to allow normal postnatal survival, growth & development as a child. Premature infants are at greater risk for short & long term complications, including disabilities & obstruction in growth & mental development. Preterm birth is by far the most common cause of prematurity & is the major cause of neonatal mortality in developed countries. Whereas the usual definition of preterm birth is birth before 37 weeks gestation, a premature infant is one that has not yet reached the level of fetal development that generally allows life outside the womb. LBW
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Signs & symptoms Anthropometry

Classification

Length is less than 47 cm. Head circumference is usually less than 33cm Fontanels are large & sutures are widely separated. Face face is small Ears cartilage is soft & the ear recoil is poor Scalp hairs are wooly Skin is thin, pink with abundant lanugo & little vernix caseosa. Subcutaneous fat is deficient Breast nodule is not palpable In males scrotum is pinkish with less rugae. Testes may be absent in the scrotum. In females labia minora is not covered by libia majora.

Genitalia

Specific risks for the preterm neonate

however, an association does not establish causality.

Maternal background

Preterm infants usually show physical signs of prematurity in reverse proportion to the gestational age. As a result they are at risk for numerous medical problems affecting different organ systems. Neurological problems include apnea of prematurity, hypoxic ischemic encephalopathy (HIE), retinopathy of prematurity (ROP), developmental disability, cerebral palsy & intraventricular hemorrhage, Cardiovascular complications may arise from the failure of the ductus arteriosus to close after birth : patent ductus arteriosus (PDA), pulmonary haemorrhage. Respiratory problems are common, specifically the respiratory distress syndrome (RDS) or HMD (hyaline membrane disease), chronic lung disease BPD (bronchopulmonary dysplasia)congenital pneumonia, apnoea. Gastrointestinal poor gastric motility & necrotizing enterocolitis (NEC). Hematologic complications include anemia of prematurity, thrombocytopenia, vitamin K deficiency & hyperbilirubinemia (jaundice) that can lead to kernicterus. Metabolic problems arise from hypoglycemia, hypocalcaemia, metabolic acidosis, Infection, including sepsis, pneumonia & urinary tract infection
Causes

Labor is a complex process involving many factors. Four different pathways have been identified that can result in preterm birth & have considerable evidence : 1) Precocious fetal endocrine activation, 2) Uterine over distension, 3) Decidual bleeding, and 4) Intrauterine inflammation/infection. Activation of one or more of these pathways may happen gradually over weeks, even months. From a practical point a number of factors have been identified that are associated with preterm birth;
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(BOH) bad obstetric history Low socio economic status Maternal age under 16 & above 35 years Women with a low BMI & poor nutritional status Obesity does not directly lead to preterm birth; however, it is associated with diabetes & hypertension which are risk factors by themselves Women with a previous preterm birth are at higher risk for a recurrence at a rate of 1550%. Marital status is associated with risk for preterm birth. Genetic make - up is a factor that can cause preterm birth. Multiple pregnancies (twins, triplets, etc.) The use of fertility medication that stimulates the ovary has been implicated as an important factor in preterm birth. Maternal medical conditions increase the risk of preterm birth; such conditions include high blood pressure, pre - eclampsia, maternal diabetes, asthma, thyroid disease & heart disease. Obstetric abnormalities like incompetent cervix, short cervical length, uterine malformations like tumors, placenta previa, bicornuate uterus the capacity of the uterus to hold the growing pregnancy may be limited & preterm labor ensues. Abnormal amounts of amniotic fluid, too much (polyhydramnios) or too little (oligohydramnios) are also at risk. The mental status of the women is of significance. Anxiety & depression have been linked to preterm birth. Addiction - the use of tobacco, cocaine, excessive alcohol during pregnancy also increases the chance of preterm delivery. Babies with birth defects are at higher risk of being born preterm. The frequency of infection in preterm birth is inversely related

Infection

to the gestational age. A number of maternal bacterial infections are associated with preterm birth including pyelonephritis, asymptomatic bacteriuria, pneumonia & appendicitis.

Prevention Glucocorticosteroids

developing countries where advanced equipment & even electricity may not be available or reliable, simple measures such as (KMC) kangaroo mother care (skin to skin warming), encouraging breastfeeding & basic infection control measures can significantly reduce preterm morbidity & mortality. Phototherapy may be used to treat newborn jaundice (hyperbilirubinemia).
Prognosis

Severely premature infants may have underdeveloped lungs, as they do not produce their own surfactant. This directly leads to respiratory distress syndrome, also called hyaline membrane disease, in the neonate. For this reason pregnant mothers with threatened premature delivery prior to 34 weeks are often administered at least one course of glucocorticoids. The steroid crosses the placental barrier & stimulates the production of surfactant in the lungs of the fetus. Typical glucocorticoids that are used for the above purpose are betamethasone or dexamethasone, often when the fetus has reached viability at 23 weeks. In cases where premature birth is unavoidable, a second rescue course of steroids can be administered 12 to 24 hours before the anticipated birth. Besides reducing respiratory distress, other neonatal complications are reduced by the use of glucocorticosteroids, namely intraventricular haemorrhage, necrotising enterocolitis & patent ductus arteriosus.
Neonatal care

Most children even if born very preterm adjust very well during childhood & adolescence. As survival has improved, the focus of interventions directed at the newborn has shifted to reduce long term disabilities, particularly those related to brain injury. The risks of medical & social disabilities extend into adulthood & are higher with decreasing gestational age at birth & include cerebral palsy, mental retardation, disorders of psychological development, behavior & emotion, disabilities of vision & hearing & epilepsy. Weight generally correlates to gestational age; however, infants may be underweight for other reasons than a preterm delivery. 1) Low birth weight (LBW) have a birth weight of less than 2500 g (5 lb 8 oz) & are mostly but not exclusively preterm babies as they also include small for gestational age (SGA) babies. 2) Very Low Birth Weight (VLBW) which is less than 1500 g & 3) Extremely Low Birth Weight (ELBW) which is less than 1000 g. Almost all neonates in the latter two group are born preterm.
Post term

In developed countries premature infants are usually cared for in a neonatal intensive care unit (NICU). The pediatricians who are specialized in the care of very sick or premature babies are known as neonatologists. In the NICU, premature babies are kept under radiant warmers or in incubators (also called isolettes), which are bassinets (?????) enclosed in plastic with climate control equipment designed to keep them warm & limit their exposure to germs. Modern neonatal intensive care involves sophisticated measurement of temperature, respiration, cardiac function, oxygenation & brain activity. Treatments may include fluids & nutrition through intravenous catheters, oxygen supplementation, mechanical ventilation support & medications. In
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Postmaturity is when a baby has not yet been born after 42 weeks of gestation. Post - term, post maturity, prolonged pregnancy & post - dates pregnancy all refer to post mature birth. Post - mature births do not have any harmful effects on the mother, but the fetus, however, can begin to suffer from malnutrition. After the 42nd week of gestation, the placenta, which supplies the baby with nutrients & oxygen from the mother, starts aging & will eventually fail. If the fetus passes fecal matter, which is not typical until after birth & the child breathes it in, then the baby is at the risk of developing meconium aspiration syndrome.

Causes

The causes of post - term birth are unknown. But post - mature births are more likely when the mother has experienced a previous post - mature birth. Due dates are easily miscalculated when the mother is unsure of her last menstrual period. When there is a miscalculation, the baby could be delivered before or after the expected due date. Post - mature births can also be attributed to irregular menstrual cycles.

Breaking the water - Having ones water broken feels like a slight tug & then a warm flow of liquid. Pitocin - When the synthetic hormone, pitocin, is used, contractions occur more frequently than a natural occurring birth, they are also more intense. Pitocin doesnt have the natural effects of stress relief that the naturally occurring hormone, oxytocin, does.

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Definitions 1) Fetus It is defined as a product of conception, irrespective of

Symptoms

Different babies will show different symptoms of post maturity. The most commons symptoms are dry skin, overgrown nails, creases on the babys palms & soles of their feet, minimal fat, a lot of hair on their head & either a brown, green, or yellow discoloration of their skin.
Complications

2)

Towards the end of pregnancy calcium is deposited on the walls of blood vessels & proteins are deposited on the surface of the placenta, which changes the placenta. This limits the blood flow through the placenta & ultimately leads to placental insufficiency & the baby is no longer properly nourished. Post - term babies may be larger than an average baby, thus increasing the length of labor. The labor is increased because the babys head is too big to pass through the mothers pelvis. This is called cephalopelvic disproportion. When post - mature babies are larger than average forceps or vacuum delivery may be used to resolve the difficulties at the delivery time. Difficulty in delivering the shoulders, shoulder dystocia, becomes an increased risk.

3)

4)

5)

the duration of the pregnancy & which is not expelled or extracted from the mother. Live birth It is defined as complete expulsion or extraction from the mother of a product of conception, irrespective of the duration of the pregnancy & which after separation, breathes or shows any other evidence of life such as beating of heart, pulsation of umbilical cord or definite movements of voluntary muscles irrespective of the attachment of placenta to the cord. Still birth A product of conception that after expulsion or separation from mother does not show any evidence of life at gestational age of 20 wks or more or weighing more than 500 gm. Fetal death Death prior to complete expulsion or extraction from its mother of a product of conception irrespective of duration of pregnancy & death indicated by absence of any signs of life. Birth weight The first weight recorded of a live or still bon baby preferably taken within first hour of life.

What it feels like Stripping the membranes - Stripping the membranes only takes

Birth weight groups LBW Baby born with birth weight less than 2500 gm VLBW
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a few minutes & causes a few intense cramps. Many women report a feeling similar to urination.

(up to 2499 gm) irrespective of gestational period. Baby born with birth weight less than 1500 gm (up to 1499 gm)

ELBW

Baby born with birth weight less than 1000 gm

(up to 999 gm)

Gestational age

It is calculated from the first day of LMP till the date of birth & is always expressed in completed weeks.
Gestational age groups 1) Pre term Baby born with a gestational age of less than 37 2) 3)

wks (< 259 days) irrespective of birth weight. Term Baby born with a gestational age between 37 41 wks (259 293 days) irrespective of birth weight. Post term Baby born with a gestational age of 42 wks (294 or more) irrespective of birth weight.

In utero, most of the blood flow is shunted away from the lungs & directed to the placenta where fetoplacental gas exchange occurs. Fetal pulmonary vascular resistance (PVR) is high & the fetal systemic vascular resistance (SVR) is low. Within minutes of delivery, the newborns pulmonary vascular resistance decreases, causing a corresponding increase in neonatal pulmonary blood flow. At birth, the lungs must transition (change) rapidly to become the site for gas exchange, or cyanosis & hypoxia rapidly develop. The fetal lung is filled with approximately 20 mL fluid at term. Fetal airways, alveoli & terminal saccules are open & stable at normal fetal lung volumes, distended by lung fluid secreted by the pulmonary epithelium. This lung fluid maintains lung volume at about functional residual capacity & determines normal lung growth. A constant flow of this fluid is secreted into the alveolar spaces throughout development, which contributes to the fetal amniotic fluid. Pulmonary & bronchial circulation also develops as the alveoli appear. Because of the compressive effect of the fetal lung fluid & the low partial pressure alveolar oxygen (paO2) in utero, the pulmonary capillary bed & pulmonary blood vessels remain constricted. High vascular resistance & low pulmonary blood flow results. The placenta provides the respiratory function for the fetus. Two major characteristics of placental circulation enable the placenta to maintain adequate oxygenation of the fetus. First, the placenta has a multi villous circulation that allows for maximum surface area for the exchange of oxygen & carbon dioxide between the mother & fetus. Second, several factors result in the lowering of maternal pH & increasing of fetal pH, which results in increased transfer of oxygen from the maternal

Fetal pulmonary physiology

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Neonatal resuscitation

Resuscitation (rise again) involves knowing much more than an ordered list of skills & having a resuscitation team; it requires excellent assessment skills & a thorough understanding of fetal & neonatal physiology.
The physiology of transaction

Neonatal transition requires spontaneous breathing & successful cardiopulmonary changes, as well as other changes to independent organ system functions. A thorough understanding of normal transitional physiology leads to a better understanding of the needs of the infant who is experiencing difficulties and, therefore, should result in a more effective resuscitative effort. Following birth, for the lungs to operate as a functional respiratory unit providing adequate gas exchange, the airways & the alveoli must be cleared of fetal lung fluid; pulmonary blood flow must increase & spontaneous respiration must be established.
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Respiratory adaptation

to the fetal hemoglobin or RBCs. Maternal blood, carrying oxygen on adult hemoglobin, releases oxygen to the fetal circulation & accepts both carbon dioxide & various byproducts of metabolism from the fetal circulation. These transfers result in a decrease in the maternal placental blood pH & a corresponding shift of the maternal oxygen dissociation curve to the right, which results in a lower affinity of the hemoglobin for oxygen & the release of additional oxygen to the fetal hemoglobin. The corresponding shift in the fetal oxygen - dissociation curve to the left allows the fetal hemoglobin to bind more oxygen. Fetal breathing, or chest wall & diaphragmatic movement, begins at approximately 11 weeks gestation & increases in strength & frequency throughout gestation. Fetal breathing is controlled by chemoreceptor located in the aorta & at the bifurcation of the common carotid. These areas sense both pH & partial pressure of carbon dioxide (pCO2). A reflex response to altered pH & pCO 2 is present at approximately 18 weeks gestation; however, the fetus is not able to regulate this response until approximately 24 weeks of gestation. As discussed above, the fetal airways & alveoli are filled with lung fluid that needs to be removed before respiration. Only a small portion of this fetal lung fluid is removed physically during delivery. During the thoracic squeeze, 25 - 33% of the fluid may be expressed from the oropharynx & upper airways, although this amount may be markedly less. Thoracic recoil allows for passive inspiration of air into the larger bronchioles. Effective transition requires that any remaining liquid be quickly absorbed to allow effective gas exchange. Labor is also associated with an increase in catecholamine levels
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Neonatal pulmonary physiology

that stimulate lymphatic drainage of the lung fluid. In addition, with the onset of labor, the fetus produces adrenaline & the mother produces thyrotropin - releasing hormone, which stimulates the pulmonary epithelial cells to begin reabsorption of fluid. These findings could account for the increased incidence of transient tachypnea of the newborn following birth by cesarean delivery without labor. After birth, lung fluid is removed by several mechanisms, including evaporation, active ion transport, passive movement from Starling forces & lymphatic drainage. Active sodium transport by energy - requiring sodium transporters, located at the basilar layer of the pulmonary epithelial cells, drive liquid from the lung lumen into the pulmonary interstitium where it is absorbed by the pulmonary circulation & lymphatics. Exposure to an air interface along with high concentrations of glucocorticoids & cyclic nucleotides reverses the direction of ion & water movement in the alveoli leading to highly selective sodium channels. This changes the fetal lung epithelial cells from a pattern of chloride secretion to one of sodium reabsorption accelerates reabsorption of fetal lung fluid. The first breath must overcome the viscosity of the lung fluid & the intra - alveolar surface tension. This first breath must also generate high transpulmonary pressure, which helps drive the alveoli fluid across the alveolar epithelium. With subsequent lung aeration, the intraparenchymal structures stretch & gasses enter the alveoli, resulting in increased paO2 & pH. The increased paO 2 & pH result in pulmonary vasodilatation & constriction of the ductus arteriosus. Lung expansion & aeration is also a stimulus for surfactant release with the resultant establishment of an air - fluid interface & development of functional residual capacity (FRC). Normally, 80 - 90% of FRC is established within the first hour

of birth in the term neonate with spontaneous respirations. Premature & critically ill infants with surfactant deficiency or dysfunction may have limited ability to clear lung fluid & establish a functional residual capacity. The pulmonary vascularity is stimulated to dilate by chemical mediators, nitric oxide & prostaglandins. Nitric oxide is released when pulmonary blood flow & oxygenation increases. The formation of certain prostaglandins, such as prostacyclin, is induced by the presence of increased oxygen tension. Prostacyclin acts on the pulmonary vascular smooth muscle bed to induce pulmonary vasodilatation. Prostacyclin has a short half - life in the bloodstream and, therefore, does not affect the systemic circulation. Soon after birth, fetal respiratory activity must transition to normal spontaneous breathing. To overcome the viscosity & resistance of fluid filled lungs & recoil & resistance of the chest wall, lungs & airways the infant must generate a negative pressure so that air moves from an area of higher pressure to one of lower pressure. Two major physiologic responses have been described for the initial lung inflation in the neonate. The first response is the rejection response, in which the neonate responds to positive pressure lung inflation with a positive intraesophageal pressure to resist the inflation. That is to say, the infant actively resists attempts to inflate the lungs by generating an active exhalation. This response acts to not only reduce lung inflation, but also may cause high transient inflation pressures. The second response is Heads paradoxical response in which the neonate responds to positive pressure lung inflation with an inspiratory effort, causing a negative intraesophageal pressure. This inspiratory effort, with the resultant negative, pressure produces a fall in inflation pressures but results in a transient increase in tidal volume.
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Of course, the neonate may demonstrate no response to the inflation attempt, not generating any change in intraesophageal pressure during the positive pressure inflation & passive inflation subsequently results. These physiologic responses to positive pressure inflation in the delivery room may cause large variability in the tidal volume & intrapulmonary pressures, despite constant delivery of inflation pressure. Stimuli for the first breath may be multifactorial. The environmental changes that occur with birth (e.g. tactile & thermal changes, increased noise & light) activate a number of sensory receptors that may help initiate & maintain breathing. Clamping of the cord removes the low resistance placenta, causing an increase in systemic vascular resistance & consequently causing an increase in both systemic blood pressure & pulmonary blood flow. Certain evidence also suggests that the increased arterial paO2 following the initial breaths may be responsible for the development of continuous breathing via hormonal or chemical mediators that are still undefined. When the newborn lungs fill with air, the paO2 should rise gradually. In term infants with a persistent hypoxia, an initial increase in ventilation occurs, followed by a decrease in ventilation occurs. This effect is even more profound in premature infants whose CNS is not as mature. The carotid bodies & peripheral chemoreceptor located at the bifurcation of the common carotids are stimulated during hypoxia to increase minute ventilation. In asphyxiated infants who cannot increase minute ventilation (e.g. because of extreme prematurity or sedation), profound bradycardia may result.

Cardiovascular Adaptation Fetal circulation

Neonatal circulation

The aeration of the lung results in an increase in arterial oxygenation & pH, with a resulting dilation of the pulmonary vessels. Decompression of the capillary lung bed further decreases the pulmonary vascular resistance. A corresponding decrease in right ventricular & pulmonary artery pressures is also noted. The decrease in pulmonary vascular resistance leads to an increase in blood flow to the lungs & in pulmonary venous return. Clamping of the umbilical cord removes the low resistance placental vascular circuit & causes a resultant increase total systemic vascular resistance with a resultant increase in left ventricular & aortic pressures. The increased systemic vascular resistance, combined with the decreased pulmonary vascular resistance, reverses the shunt through the ductus arteriosus (from right - to - left shunting to left - to - right shunting) until the ductus completely closes. All of these peripartum events result in closure of the other fetal shunts. With the decrease in right atrial pressure & the increase in left atrial pressure, the one - way flap - valve foramen ovale is pushed closed against the atrial septum. This functional closure at birth is followed by anatomical closure that usually occurs at several months of age. The ductus venosus closes because of the clamping of the umbilical cord, which terminates umbilical venous return. Functional mechanical closure of the ductus venosus is accomplished by the collapse of the thin - walled vessels. Anatomical closure subsequently occurs at approximately 1 2 weeks. Permanent closure of the ductus venosus may be delayed in preterm infants or infants with persistent pulmonary hypertension. The constriction & closure of the ductus arteriosus is accomplished by contractile tissue within the walls of this blood vessel. The contraction of this tissue is dependent on
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both the increase in arterial oxygen related to the onset of spontaneous respirations & a fall in circulating prostaglandin E2 (PGE2).
Response to Asphyxia

The fetus or newborn that is subjected to asphyxia begins a diving reflex (so termed because of certain similarities to the physiology of diving seals) in an attempt to maintain perfusion & oxygen delivery to vital organs. Hypoxia & acidosis leads to pulmonary arteriolar vasoconstriction. Pulmonary vascular resistance increases, leading to a decreased pulmonary blood flow & increased blood flow directly to the left atrium. Systemic cardiac output is redistributed, with increased flow to the heart, brain & adrenal gland & decreased flow to the rest of the body. Early in the course of asphyxia, systemic blood pressure increases. However, with ongoing hypoxia & acidosis, the myocardium fails & bradycardia occurs; this causes a decrease in blood pressure & tissue perfusion, leading to eventual tissue ischemia & hypoxia. Infants who are undergoing asphyxia have an altered respiratory pattern. Initially, they have rapid respirations. These respiratory efforts eventually cease with continued asphyxia (termed primary apnea). During primary apnea, the infant responds to stimulation with reinstitution of breathing. However, if the asphyxia continues, the infant then begins irregular gasping efforts, which slowly decrease in frequency & eventually cease (termed secondary apnea). Infants who experience secondary apnea do not respond to tactile or noxious stimulation & require positive - pressure ventilation (PPV) to restore ventilation. Primary & secondary apnea cannot be clinically distinguished. Therefore, if an infant does not readily respond to stimulation, PPV should be instituted as outlined in the Neonatal

Resuscitation Program guidelines. If an infant is experiencing primary apnea, the stimulation of the ventilatory efforts causes the infant to resume breathing. If the infant is in secondary apnea, PPV is required for a longer period. The longer the infant is asphyxiated, the longer the onset of spontaneous respirations is delayed following the initiation of effective ventilation through the use of PPV.

A large number of ante partum & intrapartum maternal conditions carry an increased risk for intrapartum asphyxia.
Equipment

Preparation for Resuscitation Rapid Assessment

Newborn infants who need extensive resuscitation should be rapidly identified. Term infants with clear amniotic fluid, adequate respiratory effort & good muscle tone should receive routine care. Routine care includes provision of warmth, clearing of airway (if needed), drying the infant & assessing the color. These infants should remain with their mothers during & after routine care. Infants who do not meet criteria for routine care need additional steps in their resuscitation. This includes the initial stabilization (provide warmth, position, clear the airway, dry, stimulate & reposition). It may also include ventilation, chest compressions & medications. The goals of resuscitation are to assist with the initiation & maintenance of adequate ventilation & oxygenation, adequate cardiac output & tissue perfusion & normal core temperature & serum glucose. These goals may be attained more readily when risk factors are identified early, neonatal problems are anticipated, equipment is available, personnel are qualified & available & a care plan is formulated.

Anticipation

Causes of Depression & Asphyxia

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The delivery room should be equipped with all the necessary tools to successfully resuscitate a newborn of any size or gestational age. The equipment should include a radiant warmer, warmed blankets, a source of oxygen, instruments for visualizing & establishing an airway, a source of regulated suction, instruments & supplies for establishing intravenous access, trays equipped for emergency procedures & drugs that may be useful in resuscitation. The minimum equipment necessary includes the following : Respiration - o Oxygen supply o Assorted masks o Neonatal AMBU bag & tubing to connect to an oxygen source o Manometer o Endotracheal tubes (2.5 - 4) o Tape & scissors o Laryngoscope (0 & 1 sized blades) o Extra bulbs & batteries o CO2 detectors o Stylettes for endotracheal tubes (optional) o Laryngeal mask Airway (optional) Suction - o Bulb syringe o Regulated mechanical suction o Suction catheters (6F, 8F, 10F) o Suction tubing o Suction canister o Feeding tube (8F catheter) o Syringe, catheter tipped, 20 mL o Meconium aspirator Fluids - o Intravenous catheters (22 g)

Drugs Procedures

Tape & sterile dressing material Dextrose 10% in water (D10W) Isotonic saline solution T - connectors Syringes, assorted (1 - 20 mL) Epinephrine (1 :10, 000) - o Umbilical catheters (2.5F, 5F) o Chest tube (10F catheter) o Sterile procedure trays (e.g. scalpels, hemostats, forceps)

o o o o o

Trained Personnel

For all deliveries, at least one person should be present who is skilled in neonatal resuscitation & has responsibility for only the infant. This person must be skilled in initiation of resuscitation, use of bag mask ventilation & performance of chest compressions. Additional personnel should be immediately available to assist in tasks that may be required as part of the resuscitation, including intubation, medication administration & emergency procedures, if needed. If the delivery is identified as high risk, 2 or more skilled individuals should be assigned for the infant at delivery.

Resuscitating Neonates Thermoregulation

Preventing heat loss during the resuscitation is essential. Intrauterine thermoregulation is passive, with no use of calories or oxygen by the fetus. This intrauterine thermoregulation therefore allows for maximal intrauterine growth without fetal energy expenditure for thermal homeostasis. Brown fat storage begins during the third trimester. Brown fat may be used for heat production in the newborn period. Several factors lead to increased heat losses in the newborn infant. The neonate has a large skin surface areatobody weight ratio, which increases heat & fluid evaporative loss.
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The fluid loss from the skin (not due to sweating but caused by direct transdermal water loss) results in massive heat loss. The thin skin with blood vessels that are near the surface provides poor insulation, leading to further heat loss. Additionally, the newborn infant (especially if premature) has a limited capacity to change body position for heat conservation. Animals ordinarily attempt to decrease heat loss by decreasing exposed surface area (i.e. curling up). This reduction in exposed surface area is accomplished by assuming a flexed position; however, premature, critically ill & depressed infants are unable to accomplish flexed positioning. Neonates have a very limited capacity for metabolic heat production. The newborn infant has limited energy stores, largely because of decreased subcutaneous fat & brown fat stores. This paucity of fat stores is more pronounced in premature & growth - retarded infants. Additionally, infants do not shiver effectively, which is a major source of heat production in the adult. The main source of heat production in the newborn is nonshivering thermogenesis. Thermo receptors in the face have a marked sensitivity to heat & cold. Stimulation by cold leads to norepinephrine production & thyroid hormone release causing brown fat to be metabolized. Brown fat is highly vascularized & stored in pockets around the neonates body. When brown fat is metabolized, triglycerides are hydrolyzed to fatty acids & glycerol. Additionally, glycolysis is initiated & glycogen stores are used, both processes resulting in glucose production. Heat is produced as a byproduct of the increased metabolic rate & oxygen consumption. Infants who experience heat loss have an increased metabolic rate & use more oxygen. Increased oxygen consumption can be dangerous in infants who are experiencing respiratory compromise. The addition of cold stress in infants who are poorly oxygenated

potentially can lead to a change from aerobic to anaerobic metabolism. This change in metabolism may lead to tissue hypoxia & acidosis because of the buildup of metabolic byproducts such as lactate. Because of the inefficiency of anaerobic metabolism, the infant uses up glucose & glycogen reserves rapidly & still produces only a limited amount of energy for heat production. Therefore, cold stress can lead to both metabolic acidosis & hypoglycemia. Infants with asphyxia have thermoregulatory instability & hypothermia delays recovery from acidosis. The environmental temperature is also important in controlling heat loss in the newborn. As a fetus, the thermal environment is precisely regulated by the mothers core temperature & heat losses are nonexistent. Following delivery, even when drying & a radiant heat source are used, infants continue to lose large amounts of heat. Heat losses are related to the differences both in water concentrations between the skin & the air as well as the absolute temperature gradient. The primary goal in neonatal thermoregulation is to prevent heat loss, as opposed to later rewarming a cold infant. Ideally, an area (e.g. a stabilization room) should be separate from the operating room or labor room; this allows special attention to the unusual thermal & environmental needs of the newborn high - risk infant. This stabilization area should be kept as warm as possible, balancing the requirements of the high - risk infant with the comfort of the adult staff in that area. Low delivery room temperatures can predispose to hypothermia & NRP guidelines recommend that if a preterm delivery is anticipated, the delivery room temperature should be increased. A potential approach to delivery room temperatures is to have a dedicated room in which ambient temperature can be well controlled Newborns should be dried with pre - warmed blankets or towels
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& placed on a pre - warmed heat source. Open bed warmers, which use radiant heat, are used in most delivery rooms. They provide warmth during resuscitation & for any subsequent invasive procedures. It is important for the practitioner to keep in mind that this source of heat does not protect the infant from evaporative heat loss but, instead, encourages evaporative heat losses. Continuous monitoring of temperature should occur as soon as possible after the delivery. Premature infants (< 1500 g) should be covered in plastic wrap (polyethylene) to prevent excessive heat loss. A full resuscitation, including line placement, can & should be performed with the plastic wrap in place. A woolen head cap should be used. Weights should be obtained on radiant warmer bed scales. Adequately warming the transport incubator is essential. The infants temperature should be documented as soon as possible after birth & every 10 - 15 minutes thereafter until continuous temperature monitoring has been established. Another common source of heat loss in the newborn infant undergoing resuscitation is the use of unheated non - humidified oxygen sources for the bag - valve - mask device. Inspired gasses that are sent to the lungs are subsequently heated & humidified by the infant, thus resulting in massive heat exchange due to evaporative heat losses & insensible water loss. Therefore, whenever possible, warmed & humidified gasses should be provided in the resuscitation area. Alternatively, the intubated & ventilated infant should be placed on a heated ventilator circuit as soon as is feasible.
Airway management

Once the infant is placed in a heated environment, the infant should be positioned to open the airway & the mouth & nose should be suctioned. A bulb syringe should be used for the initial suctioning. Infants have a vagal reflex response to sensory stimulation of the larynx, which may induce apnea, bradycardia, hypotension & laryngospasm. Therefore, the act of suctioning the posterior oral airway or the trachea with a catheter because of extremely

thick or meconium - stained fluids may cause profound central apnea, bradycardia & laryngospasm. This reflex bradycardia may be profound. Therefore, deep suctioning of the trachea should be limited to infants who have thick mucous that cannot be removed by bulb syringe or used for the aspiration of aspirate stomach contents, when necessary. The instillation of saline into the trachea also has been shown to stimulate the afferent sensory neurons leading to these sequelae & has no place in the immediate resuscitation period. Lung inflation has been shown to reverse the effects of vagal stimulation. Vigorous suctioning of the nares with a catheter can lead to edema of the nasal tissues with resulting respiratory distress after the infant leaves the delivery room. Wall suction should be set so that pressures do not exceed 100 mm Hg. Drying & suctioning often is enough stimulation to initiate breathing; however, if more vigorous stimulation is necessary, slapping the soles of the feet or rubbing the back may be effective. The back should be visualized briefly for any obvious defect in the spine before beginning these maneuvers. If there is no response to stimulation, it may be assumed the infant is in secondary apnea & PPV should be initiated. At this point, the infants respiratory rate, heart rate & color should be evaluated. Most infants do not require further intervention. This is considered routine care for most term infants with clear amniotic fluid who are actively breathing & crying & have good muscle tone. Infants who do not meet the criteria for routine care or have difficulties with respiratory effort, tone, or color need further intervention. Further resuscitative efforts should be guided by simultaneous assessment of respirations, heart rate & color.
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Stimulation

Most infants need observational care. Neonatal transition occurs over time. Infants who have a sustained heart rate of more than 100 beats per minute (BPM) & adequate respiratory effort but who remain cyanotic should receive blow - by oxygen via oxygen tubing or a mask. Supplemental oxygen should be initially provided, with a fraction of inspired oxygen (FiO2) of 1 at a flow rate of 8 - 10 L/ min. If supplemental oxygen is to be provided for a prolonged period, then heated humidified oxygen should be supplied via an oxy hood, with the FiO2 adjusted to result in pulse - oximetry saturations of 92 - 96% in the term infant & 88 - 92% in the preterm infant. Term infants may also be resuscitated with a FiO2 of less than 1, but it should be increased if the infant does not improve within 90 seconds. In premature infants, oxygen should be on a blender & blended up or down to keep the infants saturations around 90%. If a blender is not available, an FiO2 of 1 should be used & has not been shown to be detrimental to premature infants for a brief duration. For a number of reasons (discussed above), it can be difficult for the infant to clear fluid from the airways & establish air filled lungs. Initial respiratory efforts may need to be augmented by the addition of either continuous positive airway pressure (CPAP) or PPV. Post resuscitative care is the term used for infants who require a more extensive resuscitation. The addition of positive pressure aids in the development of functional residual capacity & is needed more commonly in premature infants. Mechanical lung inflation is also important to reverse persistent bradycardia in an apneic asphyxiated infant. Infants with adequate respirations who are having respiratory distress manifested by tachypnea, grunting, flaring, retracting,

Positive - pressure ventilation

Supplemental oxygen

or persistent central cyanosis may benefit from positive end expiratory pressure (PEEP), CPAP, or both. If the infant is apneic, have inadequate respiratory efforts (gasping), or a heart rate of less than 100 BPM, PPV should be initiated immediately. Infants who have continued central cyanosis despite supplemental oxygen should also receive PPV. The ideal bag is equipped to deliver positive end - expiratory pressure & the appropriately sized mask should be applied firmly to the face. Ventilation provided with a flow - inflating bag, a self inflating bag or a pressure - limited T - piece have been shown to be equally effective. A T - piece resuscitator device gives a measured pressure through a mask with a thumb occlusion & provides PEEP. It has been shown to be just as effective as flow - inflating & self - inflating bags. It allows for a more precise delivery of inflation pressure & inspiratory times. In term infants, a FiO2 of 1 should be used when PPV is started. If an FiO2 of less than 1 is used, the oxygen should be increased to 1 if the infant does not respond within 90 seconds. If supplemental oxygen is not available, room air should be used to deliver PPV. Premature infants (< 32 wk) who require PPV should begin with oxygen concentrations between room air & 100% to maintain an oxyhemoglobin concentration of around 90% based on pulse oximetry. If the oxyhemoglobin concentration rises to about 95%, oxygen should be weaned. Any infant who does not respond to PPV with a heart rate of about 100 BPM should be placed on an FiO2 of 1 & have the mask repositioned. Some infants respond to brief mechanical ventilation & subsequently begin independent ventilation; others need continued ventilatory support. Sufficient, but not excessive, initial pressure must be used to
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adequately inflate the lungs, or bradycardia & apnea will persist. A pressure manometer should always be used with a pressure release valve, limiting the positive pressure to 30 - 40 cm H2 O during the first breaths. This may need to be reduced to 20 - 24 cm H2 O in preterm infants with an increase in pressures if the chest does not rise or the heart rate does not rapidly increase. To provide adequate distending pressure, the infant must be properly positioned & the upper airway must be cleared of secretions; the mask must be the correct size & form a tight seal on the face. The primary measure of adequate initial ventilation when providing assisted breaths is a rapid increase in heart rate. A rise & fall in the chest wall movement is not always adequately assessed. If no chest rise occurs, either the airway is blocked or insufficient pressure is being generated by the squeezing of the bag. Ventilatory rates of 40 - 60 BPM should be provided initially, with proportionally fewer assisted breaths provided if the infants spontaneous respiratory efforts increase. At the moment of delivery & first breath, the neonatal lung is converting from a fetal, non aerated status to a neonatal status. The neonatal lung has a requirement for gas exchange & this requires the development of a functional residual capacity with the resorption of lung fluid & the resolution of most of the atelectasis. Therefore, initial slow ventilation with more prolonged inspiratory times may be useful to assist in this task, balanced with the avoidance of inappropriate inspiratory pressures. Flow - controlled, pressure - limited mechanical devices are acceptable for delivering PPV. These mechanical devices control flow & limit pressure & have been shown to be more consistent than bags. Self - inflating & flow - inflating bags remain a standard of care. Laryngeal mask airways have been shown to be effective

for assisted ventilation when bag mask ventilation & intubation are unsuccessful. Premature infants are at high risk for lung injury from large volume inflation. Monitoring the pressure used in these patients & providing consistent inflations without high pressures is essential. Initial inflation pressures of 20 - 25 cm H2 O is usually adequate. Higher pressures may be needed if no improvement in heart rate or chest movement is noted. CPAP may be beneficial in premature infants once they are breathing spontaneously. The effectiveness of assisted ventilation should be evaluated by observing an increase in heart rate. Other signs that should be monitored include improvement in color, spontaneous breathing & improvement in muscle tone. All of these signs should be assessed within 30 seconds of PPV administration. Infants may require tracheal intubation if direct tracheal suctioning is required, effective bag - mask ventilation cannot be provided, chest compressions are performed, endotracheal administration of medications is desired, congenital diaphragmatic hernia is suspected, or a prolonged need for assisted ventilation exists. An appropriate blade (Miller size 0 or 1) should be chosen depending on the size of the infant. Premature infants may be more easily intubated with a size 0 blade & term infants require a size 1 blade. An appropriate size of endotracheal tube should be chosen based on the weight of the infant. Upon insertion of the endotracheal tube, the tube should be advanced until the vocal cord guide mark near the distal tip of the tube is visualized to be slightly past the vocal cords. This guide mark is positioned a variable distance from the distal tip (depending on the endotracheal tube size) & is designed to result in the placement of the tube tip between the vocal cords
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Intubation

& the carina at the bifurcation of the right & left main stem bronchi. The endotracheal tube should then be secured & cut to an appropriate length to minimize dead space & flow resistance. Another estimate of correct placement of the endotracheal tube is to use the weight of the infant in kilograms plus 6 to arrive at the number of centimeters at which the tube should be secured at the lip. Before securing the endotracheal tube, the infant should be assessed for equal bilateral breath sounds with maintenance of oxygenation. An immediate increase in the heart rate is an excellent indicator of appropriate endotracheal tube placement. A CO2 detector can help confirm that the endotracheal tube is in the trachea & not the esophagus. The use of CO2 detectors is the only technique that has been evaluated for confirmation of endotracheal tubes in infants & should be used to confirm endotracheal intubation. An increase in the heart rate within 5 - 15 seconds of intubation is an indication of adequate ventilation & correct tube placement. Measurement of exhaled CO2 detector provides a secondary confirmation of endotracheal tube placement after intubation. CO2 detectors use a colorimetric change to indicate exhalation of CO2 gas. When CO2 detectors are used in infants with poor pulmonary blood flow with an inability to deliver sufficient CO2 to the lungs, a false negative result may occur leading to an unnecessary extubation. Ultimately, endotracheal tube position is confirmed with chest radiography. Free - flow oxygen should be provided throughout the procedure & effective ventilation should be provided via the bag or ventilator after the infant is intubated Endotracheal Tube Size & Measurement at Lip According to Infant Weight

Weight

Endotracheal Tube Size

Endotracheal Tube measurement at Lip

< 1000 g 1000 - 2000 g 2000 - 3000 g > 3000 g

2.5 endotracheal tube 2.5 - 3 endotracheal tube 3 - 3.5 endotracheal tube 3.5 - 4 endotracheal tube

7 cm at the lip 8 cm at the lip 9 cm at the lip 10 cm at the lip

Cardiovascular support & chest compressions

Most infants who present at delivery with a heart rate less than 100 BPM respond to effective ventilatory assistance with a rapid increase in heart rate to normal rates. In contrast, if an effective airway & effective ventilation is not established, further support is not effective. Chest compressions should be initiated following only 30 seconds of effective PPVs if the heart rate remains less than 60 BPM. An assessment of the heart rate can be obtained by palpating the umbilical stump at the level of insertion of the infants abdomen or by direct auscultation of the precordium. Chest compressions should be discontinued as soon as the heart rate is higher than 60 BPM. Chest compressions may be performed either by circling the chest with both hands & using a thumb to compress the sternum or by supporting the infants back with one hand & using the tips of the middle & index finger to compress the sternum. The thumb technique is preferred because of improved depth control during compressions. This technique may also generate higher peak systolic & coronary perfusion. The 2 - finger technique may be used when access to the umbilicus is required. Pressure should be applied to the lower portion of the sternum, depressing it to a depth approximately one third of the anterior - posterior diameter at a rate of 90 inches per minute. 1 ventilation should be interposed after every 3 chest compressions, allowing for 30 breaths per minute. The chest should fully reexpand during relaxation, but the rescuers thumbs should not remain in place.
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The recommended chest compressions/ventilations ratio is 3 :1 (120 events/min). Evaluate the heart rate & color every 30 seconds. Infants who fail to respond may not be receiving effective ventilatory support; thus, constantly evaluating ventilation is imperative. Chest compressions should be discontinued when the heart rate is 60 bpm or higher. Neonatal resuscitation drugs should be stocked in any area in which neonates are resuscitated, including each delivery & stabilization area, as well as the emergency room. Personnel should be familiar with neonatal medications, concentrations, dosages & routes of administration. Drugs currently recommended include epinephrine (1 :10, 000) & isotonic sodium chloride solution (0.9%) as an intra - vascular volume expansion agent. Epinephrine use should be considered only when the heart rate is less than 60 BPM & ventilation has been established & provided for at least 30 seconds. The only exception to this rule may be in infants who are born without a detectable pulse or heart rate. The current recommended dose for epinephrine is 0.01 - 0.03 mg/kg (0.1 - 0.3 mL of the 1 :10, 000 solutions) intravenously administered. Intravenous administration is the preferred route. Higher intravenous doses are not recommended & the post - resuscitation hypertension could put premature infants at risk for intraventricular hemorrhage. If vascular access cannot be obtained epinephrine may be given via the endotracheal tube but the dose should be increased to 3 times that of the intravenous dose. Ensure that the small volume is not deposited on the endotracheal tube connector or in the lumen of the tube. The administration of epinephrine may be followed with 0.5 1 mL of saline to ensure that the drug is delivered to the lung,

Medications

where it is absorbed & delivered to the heart. If an umbilical venous catheter is used for medication administration, the catheter should be inserted only until blood flow is obtained, usually 3 - 5 cm. Because the dosing recommendations for epinephrine have included the endotracheal route of administration, the need for emergent placement of umbilical venous catheters has been reduced markedly in the delivery room. In an editor s note commenting on an article entitled Cardiopulmonary Resuscitation in the Delivery Room, Catherine DeAngelis writes, .... check the airway (optimize
respiratory support) one more time before compressing the chest. More often than not, you & the infant can then take deep breaths & you can beat your own chest instead of the infants.

Sodium bicarbonate had previously been recommended in the delivery room to reverse the effects of metabolic acidosis related to hypoxia & asphyxia. However, recent studies show that 0.9% saline provides better cardiac & blood pressure support to correct both the acidosis & the underlying etiology of the metabolic acidosis. Use of sodium bicarbonate in the delivery room has been associated with an increased incidence of intraventricular hemorrhage in very low birthweight infants. Sodium bicarbonate, however, may be useful in prolonged arrest after adequate ventilation is established. A dose of 2 mEq/kg may be intravenously administered. If sodium bicarbonate is used in the face of a persistent respiratory acidosis & elevated pCO2, the acidosis is not corrected. Volume expansion may be used in neonates with evidence of acute blood loss or with evidence of shock of any etiology. In general, the neonatal heart responds well to the increase in preload at the atrial level caused by the volume expansion. Hypovolemia may be masked in a newborn infant because of the significant peripheral vasoconstriction caused by the elevated catecholamines following delivery. Systolic blood
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pressure also may be elevated falsely with pain. The current recommendations for volume expansion during resuscitation include isotonic sodium chloride solution or lactated ringers, 5% albumin, Plasmanate, or O - negative blood that has been cross matched with the mother. However, because of the advantages of long shelf life, low cost, ready availability & the lack of evidence of the superiority of other agents, isotonic sodium chloride solution is the most frequently used agent for volume expansion. The currently recommended dosage for volume expansion is 10 mL/kg intravenously over 5 - 10 minutes & it may be infused more cautiously in extremely preterm infants. When blood loss is known, consider use of O - negative packed RBCs. Restoring the critical oxygen - carrying capacity is essential.

The Immediate Post - resuscitation Period Maintenance of Airway & Ventilation

The goal of delivery room management is to stabilize the airway & assure effective oxygenation & ventilation. Once initial lung recruitment is obtained, avoiding overdistention is essential. Breaths delivered by bag - mask ventilation may be difficult to control & may result in overdistention & consequent pneumothorax or pneumomediastinum. Additionally, the unheated non - humidified oxygen can quickly cool the infant via the large surface area of the lungs, resulting in hypothermia. Therefore, mechanical ventilation should be initiated as soon as possible once the infant is stabilized. Although the ideal mode of assisted ventilation is controversial, providing adequate positive end - expiratory pressure to prevent atelectasis, while at the same time preventing overinflation. Once the appropriate functional residual capacity is obtained, it is essential to use the lowest support possible to allow for adequate oxygenation & ventilation.

Oxygen saturations should be monitored continually & arterial blood gas analyses performed as needed during the initial stabilization period. Saturations should be maintained in the 90 - 96% range for the term infant & 88 - 92% in the preterm infant after the initial stabilization. In utero, nutrients are provided in their basic form. Glucose is the major energy substrate of the fetus. Fetal glucose uptake parallels maternal blood glucose concentration. The liver, heart & brain receive the greatest cardiac output and, therefore, the greatest amount of glucose. The fetus uses glucose, lactate & amino acids to store fuels that are used during transition. Neonates must develop a homeostatic balance between energy requirements & the supply of substrate as they move from the constant glucose supply of fetal life to the normal intermittent variations in the availability of glucose & other fuels. With the clamping of the cord, the maternal glucose supply is cut off. A fall in blood glucose during the first 2 - 6 hours of life occurs in healthy newborns. The blood glucose usually reaches a nadir & stabilizes at 50 - 60 mg/dL. The immediate goal of fluid & electrolyte support following resuscitation is to maintain an appropriate intravascular volume & to provide glucose homeostasis & electrolyte balance. The neonatal cardiovascular system is very sensitive to preload, requiring adequate intravascular volume to maintain adequate cardiac output. Therefore, expansion of intravascular volume with appropriate solutions (e.g. isotonic sodium chloride solution) often is considered in the neonate with inadequate blood pressure or perfusion. Additionally, as discussed in previous sections, hypoglycemia may occur rapidly in critically ill or premature infants. Blood glucose determinations should be performed as soon as possible & a continuous infusion of glucose should be started at 4 - 6
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Fluid & Electrolyte Management

mg/kg/min for those infants who are not able to tolerate enteral feedings. Dextrose boluses should be limited to symptomatic infants because they may result in transient hyperosmolarity & rebound hypoglycemia. Electrolytes, such as sodium, potassium & chloride, should not be added initially because the fluid shifts from other body compartments allow for adequate electrolyte supply until adequate renal function is documented. The practitioner should monitor the weight, clinical hydration status, urine output & serum sodium concentrations closely because inappropriate fluid overload or restriction can lead to increased mortality & morbidity. Taking the infants environment into account when calculating fluid requirements is very important. Fluid rates may be started at 60 - 80 mL/kg/d for the infant in a humidified incubator, whereas fluid rates may be much higher for the infant in a dry radiant warmer environment. Preparation of the infant for transfer to a remote nursery for subsequent care requires several considerations. First, completing all the routine care that is required of newborn infants is essential. These basics of care may be neglected in the rush to prepare the infant for transport, with potentially disastrous results. Following resuscitation, care must be taken to secure all lines, tubes, catheters & leads for transport. Monitoring in the transport environment is only possible with functioning leads in place, which is frequently difficult. Rapid & complete documentation of the resuscitation & subsequent therapies also is required for future caretakers.

Preparation for Transport

Special problems during resuscitation

This section is devoted to congenital & other neonatal conditions that may present in the delivery room & that may alter the

resuscitation. The presentation of the disease & the immediate resuscitative efforts are discussed.
Extreme Prematurity

Premature infants have special needs that must be considered during the critical period immediately following delivery if mortality & morbidity are to be decreased in this group. This population of infants is at increased risk for respiratory failure, insensible water losses, hypoglycemia & intraventricular hemorrhages. Insensible water loss in the premature infant is increased secondary to the infants poorly cornified epidermis & an immature stratum corneum, which presents little barrier to evaporative heat loss. The stratum corneum is not functionally mature until 32 - 34 weeks gestation. Differences in skin maturity, prenatal nutritional status, ventilation requirements & environmental conditions all may influence the magnitude of insensible water loss that occurs following birth. The skin is the most important route for water depletion after delivery of the extremely immature infant. Transepidermal water loss (TEWL) is highest at birth in infants who are born before 28 weeks gestation & decreases slowly with advancing gestational age. Despite declines in TEWL with advancing age, infants born before 28 weeks gestation continue to have increased TEWL for 4 - 5 weeks following birth, compared to infants born at term. Because of high evaporative loss with the accompanying heat loss, the ability to achieve & maintain thermoregulation is compromised further. The skin barrier dysfunction increases the risk for infection, especially because of organisms that colonize the skin surface (e.g. staphylococcal species). This thin skin barrier also places the extremely immature infant at risk for toxicities from topically applied substances. Additionally, skin integrity is disrupted easily by the use of adhesives, which should be limited
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in premature infants. Premature infants need increased fluid administration rates initially if they are on radiant warmers for a prolonged period. With increased parenteral fluid administration using dextrose - containing fluids, the dextrose needs to be monitored closely to ensure euglycemia. Placing infants in a humidified environment decreases transepidermal water loss, improves the maintenance of body temperature & does not delay skin maturation. Measures to decrease insensible water loss should be initiated at delivery. Because radiant warmers are used routinely at deliveries because of a need for maximal patient access, infants less than 1000 g should have a plastic blanket or other barrier applied to decrease evaporative water loss until they can be placed in a humidified environment. However, care should be taken to ensure that the barrier does not block the transmission of the radiant heat source. Premature infants are at risk for intraventricular hemorrhages & periventricular leukomalacia (PVL) secondary to their immature cerebral vascular regulation & the persistence of the germinal matrix. Ventricular hemorrhage & periventricular leukomalacia often lead to serious permanent neurodevelopmental disabilities. Prevention or reduction of the severity of these disorders may begin in the delivery room. Mechanical ventilation & fluid administration must be managed cautiously in this group of infants. Volume expansion should only be administered in the face of true hypotension. Knowledge of normal blood pressure values for infants of various gestational ages is essential. Volume expansion in the face of normal blood pressure increases the risk of intraventricular hemorrhage. Additionally, when administering hyperosmolar medications (e.g. sodium bicarbonate), slow administration is important.

Mechanical ventilation may lead to harmful fluctuations in cerebral blood flow, especially when pCO2 & pH are rapidly altered. Rapid alterations in pCO2 & pH result in acute fluctuations in the cerebral blood flow of the premature infant with immature cerebral vascular autoregulation. Premature infants are also at high risk for volutrauma caused by poor lung compliance & overventilation following the administration of exogenous surfactants if changes in lung compliance are not monitored carefully. Overventilation with excessive tidal volumes & hypocarbia are associated with chronic lung disease. Stabilization of the infant using the lowest possible peak inspiratory pressure required to oxygenate & ventilate adequately is essential. Hand ventilation of an intubated infant, especially by inexperienced personnel, often leads to inconsistent tidal volumes & pressures. Use of a mechanical ventilator designed for infants offers the advantages of more consistent tidal volumes & a reduction of the heat losses because of the use of unheated non - humidified air with hand bagging. Although artificial surfactant administration is associated with a reduction of adverse sequelae in infants, its administration may lead to hyperventilation & overdistention when not administered by experienced attentive personnel. Following the instillation of artificial surfactant, rapid reaction to changes in pulmonary compliance to prevent the onset of hypocarbia & alkalosis is essential. Following the institution of mechanical ventilation, care should be taken with airway suctioning because vigorous or frequent airway suctioning is associated with hypoxia, intraventricular hemorrhage & periventricular leukomalacia. Prematurity with respiratory distress syndrome (RDS) is not associated with mucous production in the first 24 hours of life, thus suctioning protocols should be altered to provide minimal suctioning during this time.

Airway Problems Choanal atresia

Choanal atresia is caused by a failure of embryologic regression of nasal airway tissue, thereby resulting in a partial or complete occlusion of the nasal airway. These choanal defects may be bony or membranous, with most having a bony component. Complete bilateral stenosis usually results in a neonatal respiratory emergency at birth because infants generally are obligate nasal breathers during the first 6 - 8 weeks of life. At rest, these infants usually manifest severe apnea, retractions & respiratory distress that may be relieved with crying. Wheezing or stridor may be audible with inspiration & collapse of the small airways with vigorous inspiratory effort can occur. The infant in respiratory distress should be stimulated to cry & an artificial oral airway may be used to avoid intubation. The clinical diagnosis is achieved by the inability to pass a small caliber catheter through the nasal passages. However, the act of passing catheters, especially with repeated attempts, causes nasal passage swelling in any infant with the subsequent iatrogenic occlusion mimicking the congenital condition. An alternative noninvasive method of excluding the diagnosis of complete atresia is to place a glass slide under the nasal orifices & look for fogging with expiration. Supplemental oxygen should be administered to infants with choanal atresia & an oral airway may be of assistance. If the infant remains in significant respiratory distress, intubation is necessary. Intubation relieves the obstruction so that minimal ventilation (if any) is required. This syndrome presents with micrognathia & with a resultant displacement of the tongue into the posterior pharynx, which may occlude the upper airway. A central cleft of the soft palate is usually present. Respiratory distress & cyanosis are caused by the obstruction of the upper airway.

Pierre Robin syndrome

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In the delivery room, the infant should be given supplemental oxygen & placed in a prone position in an attempt to have the tongue move forward in a dependent fashion from the posterior pharynx, relieving the airway obstruction. If the infant continues to have persistent respiratory distress, an oral airway may be placed. Alternatively, an appropriately sized endotracheal tube may be passed through the nose into the hypopharynx.
Tracheal webbing

The pathogenesis of tracheal webbing originates in the tenth week of gestation when an arrest in the development of the larynx near the vocal cords results in a residual web of tissue persisting in the airway. Approximately 75% of tracheal webs occur at the level of the vocal cords. These lesions are critical if more than 50% of the airway diameter is occluded, but this is rare. These disorders may be relatively asymptomatic at birth, with the development of distress later when activity increases & the need for airway flow increases. If the infant is manifesting severe distress, a large bore needle or catheter may be placed into the trachea to allow for gas exchange while arranging for emergency treatment. Caution must be used because inexperienced personnel may confuse this rare disorder with simple inability to visualize the vocal cords. This condition rarely is considered a life - threatening emergency; however, early diagnosis is essential to prevent further complication. The types of esophageal atresia are as follows : Type I (Esophageal atresia with a distal fistula) : This is the most common type (85%). Air is present in the stomach. A blind end upper esophageal segment is present with the distal segment of the esophagus connected to the trachea via a fistula.
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Esophageal atresia with or without tracheoesophageal fistula

Type II (Esophageal atresia only) : A blind upper & lower esophageal segment is present. Air is absent from the lower GI tract, but an air - filled blind upper pouch may be observed. Type III (H - type esophageal atresia) : An isolated fistula connects the esophagus & trachea, usually occurring at the upper portion of the trachea & esophagus. Type IV (Esophageal atresia with a proximal fistula) : This type is rare. An upper esophageal segment is present with a fistula to the trachea & a blind lower esophageal segment. Air is absent from the lower GI tract. Type V (Esophageal atresia with a double fistula) : This type is rare. An upper esophageal segment is present with a fistula to the trachea & a second fistula connects the distal esophagus & trachea. Air is present in the stomach. The most common clinical symptoms of esophageal atresia with or without an esophageal - tracheal fistula include coughing, choking & cyanosis. Infants with isolated esophageal atresia usually do not demonstrate respiratory distress immediately in the delivery room but may have excess secretions. Because secretions or oral feedings are not capable of passage into the stomach, the contents of the esophageal pouch readily reflux, placing these infants at high risk for aspiration. If at all possible, PPV should be avoided in these infants. Any positive pressure applied to the airway results in inflation of the fistula, stomach & bowel, which then results in abdominal distention. This distending pressure cannot be relieved by esophageal reflux through the atretic esophagus. Relief of the distending pressure occurs with reflux of gastric contents into the lungs via the fistula. The continued application of PPV also may lead to massive gastric distention & possible rupture. In rare emergency situations, percutaneous gastrotomy may be required to decompress the stomach; however, controlled surgical placement of a gastrostomy tube is

preferable.
Cystic hygromas

of crying or bag - valve - mask ventilation.

Pneumothorax

This condition is the result of a congenital deformity of the lymphatic channels. Lymph accumulates & may compress the airway, depending on the size & location of the lymph accumulation. Approximately 80% of these lymphatic cystic accumulations occur in the neck & may compress the trachea. These infants may present with significant respiratory distress & require immediate intubation with deep positioning of the endotracheal tube to relieve the obstruction by stinting open the airway.

Pulmonary Compression Congenital diaphragmatic hernia

The pathogenesis of this disorder is caused by the incomplete formation of the diaphragm in the fetus, resulting in a migration of the abdominal viscera into the chest during development. If the defect is large & the abdominal viscera have caused long standing compression of the developing lungs, pulmonary hypoplasia may develop. The diagnosis of diaphragmatic hernia is established frequently by prenatal ultrasonography, which allows the management to be transferred to a perinatal referral center where pediatric surgery & appropriate medical support are available, including extracorporeal bypass. In the delivery room, the infant often presents with respiratory distress. Physical signs may include a scaphoid abdomen & a shift in heart sounds to the right hemithorax. Respiratory distress in the delivery room may be caused by either a pulmonary hypoplasia or may be secondary to an expansion of the bowel caused by swallowed air. The expansion of the bowel results in compression of the lung. Delivery room management includes immediate intubation & passage of a large catheter for gastric decompression. Intubation prevents distention of the stomach & bowel contents because
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Air leak syndromes are disorders produced when a rupture of pulmonary tissue occurs with the resultant escape of air into spaces in which air would not be present normally. The incidence of pneumothorax varies with gestational age, severity of pulmonary disease, need for assisted ventilation, mode of ventilation & expertise of delivery room personnel. Following the initial rupture of a small airway or an alveolus, air may enter the perivascular & peribronchial spaces & track along the lymphatic channels. Air that dissects into the hilum results in a pneumomediastinum. Air that tracks into the pleural space manifests as a pneumothorax. Spontaneous rupture of the lung directly into the pleural space is thought to occur rarely but may be caused iatrogenically with the percutaneous insertion of a chest tube. Pneumomediastinum frequently is an isolated disorder that occurs spontaneously in infants with minimal pulmonary disease. These infants usually are asymptomatic or minimally symptomatic because air in the mediastinum is capable of escaping to the tissues of the neck. Intrathoracic tension is relieved & circulation is not compromised. Infants with a pneumomediastinum should be observed. Intervention usually is unnecessary. Pneumothorax may occur immediately in the delivery room or later when significant pulmonary disease has developed. The occurrence of a pneumothorax often is associated with PPV, but it also may occur in infants who are not receiving assisted ventilation. Following the initial air leak, the subsequent expansion of intrathoracic spaces often rapidly results in an increase of intrathoracic pressure such that there is an inability to ventilate the lungs & an inability to return venous blood to the heart. This is termed a tension pneumothorax. Infants in acute distress should have a needle aspiration

performed to evacuate the extrapulmonary air while preparation is made to place a chest tube. Symptomatic pneumothorax is managed with the insertion of a chest tube until the pulmonary leak is resolved. A chest tube may not be required if the pneumothorax is small & does not involve an infant who is not receiving PPV. Supplemental oxygen (FiO2 = 1) often is administered for 6 - 12 hours to hasten reabsorption of the trapped intrapleural air.
Miscellaneous Multiple gestations

be available in the delivery room. Because of the excess fluid in the lungs, often using high pressures & oxygen are necessary initially.
Omphalocele & gastroschisis

The delivery & subsequent resuscitation of multiple infants presents a considerable challenge to the labor & delivery team. The first consideration to be addressed with the initial prenatal diagnosis of multiple gestations is to ensure that the care of such a pregnancy is at an institution capable of providing such support for the mother & multiple infants at delivery. A minimum of 2 experienced personnel should be available for each infant, as multiple gestation infants are often born prematurely (especially with higher order gestation) & more personnel may be required for each infant. Therefore, for higher order gestation involving triplets or more, preparation to ensure the presence of appropriate personnel & equipment must be planned well in advance of the delivery. When preparing for the resuscitation of a hydropic infant, a sufficient number of skilled personnel must be in the delivery room to ensure that the multiple needs of this significantly compromised neonate can be met. Equipment should be prepared before the delivery & all personnel in the room should be assigned specific procedures, such as a paracentesis or thoracentesis, if required. These procedures may need to be performed immediately if the fluid accumulation is causing difficulties in ventilation. If the hydrops is caused by anemia, blood for transfusion should
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Gastroschisis is an abdominal wall defect lateral to the umbilicus that does not have a sac or membrane covering the bowel. In contrast, an omphalocele involves the bowel herniating through the umbilical opening, with the bowel covered by a thin membrane, unless the membrane has been ruptured intrapartum. For both omphalocele & gastroschisis, maintain adequate intravascular fluid volume, to maintain thermoregulation & to prevent bowel ischemia. Preoperatively, these infants have increased fluid requirements unless the bowel is appropriately wrapped with an airtight material. If the infant is diagnosed with an omphalocele, the blood glucose should be assessed because this defect may be associated with Beckwith - Wiedemann syndrome. Trisomy 18 is associated with this anomaly. Therefore, if the condition is recognized prenatally, amniocentesis for chromosomal analysis should be offered to the family.
Congenital anomalies

Hydrops

Severe malformations observed in the delivery room should not change the resuscitative management unless skilled & experienced care providers are able to determine that the condition is incompatible with life. The family should be involved in any decision in which no resuscitation is to occur. Infants with severe malformations should be resuscitated & stabilized until an accurate diagnosis can be made.

Controversies in Resuscitation

Neonatal resuscitation has been standardized with the development of a certification program. Evaluation & recommendations for changes in the current standards is an ongoing

process. As new research is published, it is essential to evaluate the quality of the studies & make changes in practice based on evidence. This section outlines some of the current controversies & concerns in resuscitation.
Room Air Versus 100% Oxygen

Oxygen is a drug with the potential for serious adverse effects that must be considered. Oxygen free radicals are capable of tissue injury & have been implicated in several disease states in the neonate. The use of lower oxygen concentrations when resuscitating the neonate may decrease the number of oxygen free radicals & their damaging adverse effects. In one study, resuscitation with room air was shown to be as effective as 100% oxygen at lowering pulmonary vascular resistance. Currently, supplemental oxygen should be provided whenever PPV is required during resuscitation. Free - flowing oxygen should also be used in infants with central cyanosis. Clinicians may begin resuscitation with an oxygen concentration of less than 100% & may even consider starting with room air as new research data become available. Surfactant deficiency, the primary factor in the development of RDS, is the most common cause for persistent & progressive respiratory distress in premature infants. Prophylactic dosing of artificial surfactant is performed in the delivery room before the first breath or within 15 minutes following birth. Meconium staining of amniotic fluid occurs in 10 - 15% of all deliveries & rarely is seen before 34 weeks of gestation. Of newborns born with meconium stained fluid, 60% require stabilization and/or resuscitation. Of these infants that require stabilization and/or resuscitation, 3 - 4% are diagnosed with meconium aspiration syndrome.
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Meconium aspiration in a newborn can lead to atelectasis, overdistention of the alveoli, pneumothorax, pneumonitis, surfactant deficiency & persistent pulmonary hypertension. Depressed infants should be placed on a radiant heat source & no drying or stimulation provided until they are intubated & direct tracheal suctioning is performed. A meconium aspirator should be applied directly to the endotracheal tube & continuous pressure should be applied using 120 - 150 mm Hg as the tube is removed. If meconium is obtained, it is necessary to evaluate the heart rate before a second intubation is performed. With the second intubation, the practitioner may want to consider providing PPV through the endotracheal tube after suctioning is performed. Once an infant has been stabilized, intubation & suctioning can be performed again. The obstetric & neonatal team, as well as the parents, should decide when to withhold or discontinue resuscitative. Infants whose gestational age, birth weight & congenital anomalies are associated with certain death should not be resuscitated. This may include extreme prematurity (< 23 weeks gestation), extremely low birth weight (< 400 g) & chromosomal anomalies that are inconsistent with life (e.g. trisomy 13). In other situations in which the prognosis is uncertain but the associated morbidity rate is high, parenteral desires should be considered. Discontinuing resuscitation may be justified in infants who have not responded to continuous & appropriate resuscitation for a full 10 minutes & who have no heart rate or respiratory effort (no signs of life).

Withholding & Discontinuing Resuscitation

Timing of Artificial Surfactant Administration

Intubation & Suctioning for Meconium

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Examination of newborn Anthropometry of newborn Anthropometry Pre term Full term Post term

2.5 Average 50 cm Average 35 cm Average 32 cm 2.5 3.5 kg average 50 cm. average 35 cm average 32 cm (3 cm less than head circumference)

Weight Length Head circumference Chest circumference Weight Length Head circumference Chest circumference
Skin

Look for any masses or lump present Abdominal distension may be present due to obstruction, perforation, meconium ileus etc. Look for abdominal wall defects as in trisomy 18, bladder extrophy, exomphalus, umbilical hernia Excessive crying Excessive drooling of saliva from mouth Central cyanosis Seizures Refusal to feed Difficulty in feeding Vomiting/diarrhea No passage of meconium within 24 hrs & urine within 48 hrs. Icterus seen within 24 hrs after birth Blood loss from any opening Lethargy Imbalance in body temperature

Danger signs in a newborn

Acrocyanosis is the cyanosis of extremities which is normal & is present due to cold Erythema toxicum is small, vesiculopustular papules present after 2 - 4 days of birth. It may be seen on face, trunk & extremities. Mongolian spots are greenish blue areas of pigmentation commonly seen over buttocks, back & other body parts. These disappear within first year of life.

1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11) 12)

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Breast milk is thought to be the best form of nutrition for neonates & infants. This dynamic fluid provides a diverse array of bioactive substances to the developing infant during critical periods of brain, immune & guts development. The development of the mammary gland (mammogenesis), the process through which the mammary gland develops the capacity to secrete milk (lactogenesis), the process of milk production (lactation) & the specific properties of human milk those make it unique & appropriate for human infants.

Head Face

Neck

Face should be observed for any signs of dysmorphism like low set ears. Hypertelorism, depressed nasal bridge, mongoloid slant, epicanthal folds etc. Ears should be examined for any preauricular tags Mouth should be examined for presence of natal teeth, cleft lip or plate,

Pathophysiology Mammogenesis

Neck should be examined for presence of any swelling or tumor, laxity, webbing etc.
Abdomen
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The breast begins to develop in utero, undergoing the first of many developmental changes necessary for proper breastfeeding to

occur. A bulb - shaped mammary bud can be discerned in the fetus at 18 - 19 weeks gestation. The basic unit of the mammary gland is the alveolus or acinus cell that connects to a ductule. These lactiferous sinuses drain to 15 25 openings in the nipple, allowing milk to flow to the recipient infant.
Lactogenesis

In lactogenesis, the mammary gland develops the capacity to secrete milk. Lactogenesis includes all processes necessary to transform the mammary gland from its undifferentiated state in early pregnancy to its fully differentiated state sometime after pregnancy.
The stages of lactation can be summarized as

o
o

Mammogenesis : Mammary (breast) growth occurs. The size & weight of the breast increase. Lactogenesis Stage 1 (late pregnancy) : Alveolar cells are differentiated from secretory cells. Stage 2 (day 2 or 3 to day 8 after birth) : The tight junction in the alveolar cell closes. Copious milk secretion begins. Breasts are full & warm. Endocrine control switches to autocrine (supply - demand) control. Galactopoiesis (later than 9 d after birth to beginning of involution) : Established secretion is maintained. Autocrine system control continues.

Lactation

Production & secretion of milk is dependant on maternal hormonal reflexes & reflexes in the baby. Maternal reflexes Prolactin reflexes (milk secretion reflex) Oxytocin reflexes (milk ejection or letdown reflex) Neonatal reflexes Rooting reflex Sucking reflex Swallowing reflex
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Two essential hormones (prolactin & oxytocin) During the second stage of lactogenesis, the breast becomes capable of milk production. These signals, which are in direct response to stimulation of the nipple & areola (mammae), are then relayed to the central nervous system. This cyclical process of milk synthesis & secretion is termed lactation. Lactation occurs with the help of 2 hormones, prolactin (PRL) & oxytocin. Although PRL & oxytocin act independently on different cellular receptors, their combined actions are essential for successful lactation. Prolactin reflex Milk synthesis occurs in the mammary gland epithelial cells in response to PRL. The secretion of PRL appears to be both positively & negatively regulated. PRL stimulates mammary glandular ductal growth & epithelial cell proliferation & induces milk protein synthesis. Factors enhancing prolactin reflex frequent emptying of breast frequent suckling expression of milk Inhibiting factors Bottle feeding Incorrect feeding & positioning Painful breast conditions. Oxytocin reflex The other important hormone involved in the milk ejection or letdown reflex is oxytocin. When the neonate is placed at the breast & begins suckling, oxytocin is released. The suckling infant stimulates the touch receptors that are densely located around the nipple & areola. The stimulation of the nuclei causes the release of oxytocin down the pituitary stalk & into the posterior pituitary gland, where oxytocin is stored. The infants suckling creates afferent impulses that stimulate the posterior pituitary gland. This releases oxytocin in a pulsatile fashion to adjacent capillaries, traveling to the mammary

o o

myoepithelial cell receptors that, in turn, stimulate the cells to contract. Oxytocin causes the contraction of the myoepithelial cells that line the ducts of the breast. These smooth muscle like cells, when stimulated, expel milk from alveoli into ducts & subareolar sinuses that empty through a nipple pore. Factors enhancing oxytocin reflex Sight of baby, Sound of baby, Confident mother Factors inhibiting oxytocin reflex Anxiety, Emotional stress, Worry, Pain

The emptier breast produces milk faster than the fuller one. Milk production is responsive to maternal states of well - being. Thus, stress & fatigue adversely affect a womans milk supply. The mechanism for this effect is the down - regulation of milk synthesis with increased levels of dopamine, norepinephrine, or both, which inhibit PRL synthesis. Relaxation is key for successful lactation.

Factors that lessen milk production

Neonatal reflexes helpful in breast feeding 1) Rooting reflex When the mother holds the baby for breast

1) 2) 3)

2)

3)

feeding the nipple touches the lips, cheek or side of the mouth the baby turns its head towards the stimulus & searches the nipple. Sucking reflex After accepting the nipple baby starts to suck. It consists of Drawing the nipple & areola into the mouth to form an elongated teat Nipple & areola is pressed between jaws & tongue against the palate. Squeezing movements of tongue draws the milk from lactiferous sinuses. Swallowing reflex When the mouth is filled with milk, the baby swallows it & then breathes. The suck swallow breath cycle lasts for about 1 sec. The swallowing reflex develops early in foetal life but sucking reflex develops by 32 34 wks of gestation. Milk secretion directly correlates with synthesis The regulation of milk synthesis is quite efficient. Milk synthesis remains remarkably constant at approximately 800 mL/d. However, the actual volume of milk secreted is adjusted to the requirement of the infant by feedback inhibitor of lactation, a local factor secreted into the milk; therefore, the rate of milk synthesis is related to the degree of breast emptiness or fullness.
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Dummies, bottles, pacifiers Making baby wait for feeds Giving feeds like sugar, water, gripe water, honey, formula feed either as pre lacteals or anytime. 4) Certain medications like OCP, Methergine. 5) Painful breast conditions like sore/cracked nipples & congested breast. Do not give glucose/ jaggery/ sugar/ plain water or honey before the first breastfeed. This may cause infection in the babys digestive system. This may also prevent successful establishment of breastfeeding because a baby with a full stomach may not suckle at the breast.
Duration & frequency of feeding

Breastfeeding should be given baby is hungry without any restriction of time. Feeding should be given even during the night. Feed at one breast at a time till it is empty because the initial milk (foremilk) is watery (contains sugar & proteins) & quenches the babys thirst while the milk that is secreted later (hindmilk) is rich in fats & satisfies babys hunger. After the first breast is empty, shift to the second breast.
Before discharge from the maternity home

Before discharge from the maternity home, learn to hold & position the baby properly & comfortably while breastfeeding. You should be able to give nipple & maximum possible areola (dark portion behind the nipple) in babys mouth for optimal breastfeeding. Also learn to express breast milk & storage

The first contact & feed

Biochemistry of human milk

Hold your baby in close skin to skin contact within half of delivery. Start breastfeeding as soon as the baby shows readiness to suckle. Babies are very alert in the first hour after delivery & tend to suckle easily & vigorously. It has been proved that if the baby is breastfed earlier, then it is easier for the mother to establish regular breastfeeding. This ensures that breastfeeding can continue for a sufficiently long period of time
Exclusive breastfeeding

This unique fluid actually evolves to meet the changing needs of the baby during growth & maturation. For example, early milk or colostrum has lower concentrations of fat than mature milk but higher concentrations of protein & minerals. This relationship reverses as the infant matures.
Lactose, protein & total lipid concentrations in human milk

Give only breast milk till the baby is 6 months old. Water, top milk, honey, vitamins, almonds, fruit juices or any other item should not be given during this period. These will interfere with breastfeeding & may introduce infection. Mothers milk contains enough water. Hence
even in summer, an infant does not require water.

Gripe water, Balkadu, tonics for teething or any other similar preparations are unnecessary & can be dangerous. Hence these items should not be given.
Composition of breast milk

o o

Human milk is a unique, species - specific, complex nutritive fluid with immunologic & growth - promoting properties. 1) Proteins - lactalbumin, - lactalbumin, Caseins, Growth factors, Secretory IgA. 2) Carbohydrates Lactose, Oligosaccharides, Glycopeptides, Bifidus factor 3) Lipids Fat soluble vitamins, Fatty acids, Phospholipids, Triglycerides 4) Water soluble vitamins Biotin, Folate, Niacin, Vit. C, Vit. B12 & 6, Riboflavin 5) Minerals Calcium, Magnesium, Potassium, Sodium 6) Trace elements Chromium, Cobalt, Copper, Iron, Iodine, Selenium, Zinc 7) Cells Macrophages, Leukocytes, Epithelial cells, Neutrophils, Polymorphs, Plasma cells (B cells) 8) Probiotic substances Lactobacilli, Lactic acid
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In addition to the changes from colostrum to mature milk that mirror the needs of the developing neonate, variation exists within a given breastfeeding session. This hind milk is thought to facilitate satiety in the infant. Finally, the diurnal variations in breast milk reflect maternal diet & daily hormonal fluctuations. Specific enzymes to aid neonatal digestion Human milk contains various enzymes; some are specific for the biosynthesis of milk in the mammary gland (e.g. lactose synthetase, fatty acid synthetase, thio esterase), whereas others are specific for the digestion of proteins, fats & carbohydrates that facilitate the infants ability to break down food & to absorb human milk. Three - dimensional structure of human milk Under a microscope, the appearance of human milk is truly amazing. Although it is a fluid, human milk has substantial structure in the form of compartmentation. Proteins, carbohydrates & designer fats for optimal brain development Human milk provides appropriate amounts of proteins (primarily alpha - lactalbumin & whey), carbohydrates (lactose), minerals, vitamins & fats for the growing term infant. The fats are composed of cholesterol, triglycerides, short - chain fatty acids & long - chain polyunsaturated (LCP) fatty acids. The LCP fatty acids (18 - to 22 - carbon length) are needed for brain & retinal development. Large amounts of omega - 6 & omega - 3 LCP fatty acids are deposited in the developing brain

& retina during prenatal & early postnatal growth. An infant, particularly a preterm infant, may have a limited ability to synthesize optimal levels of AA & DHA from linoleic & linolenic acid. Therefore, these 2 fatty acids may be considered essential fatty acids. The unique blend of fatty acids in the breast milk has been linked to the development of innate & adaptive immune regulation. Rather than producing better vision or greater intelligence, breast milk may protects the developing neonatal brain from injury or less optimal development by providing necessary building materials & growth factors that act synergistically rather than in isolation.

Milk lipids, which damage membranes of enveloped viruses;

and
Mucins, which are present on the milk - fat globule membrane.

Immunologic properties of human milk

Human milk immunoglobulins Human milk contains all of the different antibodies (M, A, D, G, E), but secretory immunoglobulin A (sIgA) is the most abundant. Milk - derived sIgA is a significant source of passively acquired immunity for the infant during the weeks before the endogenous production of sIgA occurs. o The antigenic specificity of the mothers sIgA in her milk is directed against the same antigens in the neonate. Other immunologic properties of human milk o In addition to antibodies, human milk has numerous factors that can affect the intestinal microflora of the baby. These factors enhance the colonization of some bacteria while inhibiting the colonization by others. o The immunologic components include Lactoferrin, which binds to iron, thus making it unavailable to pathogenic bacteria; Lysozyme, which enhances sIgA bactericidal activity against gram - negative organisms; Oligosaccharides, which intercept bacteria & form harmless compounds that the baby excretes;
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Mucins adhere to bacteria & viruses & help eliminate them from the body. Interferon & fibronectin have antiviral activities & enhance lytic properties of milk leukocytes. Human milk leukocytes o Macrophages comprise 40 - 60% of the cells in colostrum, with the remainder of cells primarily consisting of lymphocytes & polymorphonucleocytes. By 7 - 10 days postpartum, with the transition from colostrum to mature milk, the percentage of macrophages then increases to 80 - 90% at a concentration of 104 - 105 human milk macrophages per milliliter of milk. Milk leukocytes can tolerate extremes in pH, temperature & osmolality. Passive immunity from mother to recipient breastfeeding infant o While awaiting endogenous maturation of the babys own immunologic systems, various immunologic & bioactive milk components act synergistically to provide a passive immunologic support system from the mother to her infant in the first days to months after birth. Ingested milk passively immunizes the neonate.
Bioactive properties of human milk

Human milk also contains growth modulators, such as epidermal growth factor (EGF), nerve growth factor (NGF), insulin like growth factors (IGFs) & interleukins. Transforming growth factor (TGF)alpha, TGF - beta & granulocyte colony - stimulating factor (G - CSF) are also identified in human milk. Certain bioactive substances & live cells in milk appear to influence neonatal gut maturation & growth through their transfer of developmental information to the newborn.
Types of breast milk

The content of nutrients within human milk changes over time as the recipient infant matures. It also changes during feeds to meet the thirst & hunger of the baby.
1) Colostrum

b)

Hind milk

Secreted towards the end of feed Rich in fat, provides energy Satisfies hunger of the baby.

4)

Pre term milk

It is a viscous, yellow colored secretion that is secreted for about 3 5 days after birth.
Composition

Milk produced by pre maturely delivered mother More calories, high concentration of fat, proteins & sodium as needed by the pre term baby.
Benefits of breast feeding 1) To baby

Higher protein content (IgA coats immature) Low carbohydrate & fat content. High concentration of vit. ADEK Low vit B, vit C & potassium. Cells like polymorphonuclears, macrophages & T & B lymphocytes in high concentration. High mineral content.

Advantages

Antibodies & cells help in immune mechanism. Laxative action due to large fat globules helps in passage of meconium & reduces the risk of jaundice. Hence should be never discarded.
2) Transitional milk

2)

Secreted 2 wks after delivery. Changes in composition & quantity. Fat & sugar content increases. Protein & immuno globin content decreases.
3) Mature milk

Complete food Available in right quality & right time, right temp. Easily digestible & well absorbed. Low acidic pH Hygienic as passes straight into infants mouth. Protects against illnesses (otitis media, respiratory, GIT diseases, probably from heart diseases, HTN in adulthood, obesity) Prevent allergies Develops emotional bonding & security Free fatty acids promote brain growth & source of energy. Decrease the chance of infant botulinium. Breast fed babies have better visual development, cognition & IQ score in later life.
To mother

3)

It follows transitional milk. Thinner & watery.

According to phase of feeding

a)

Fore milk Secreted at start of the feed. Low fat, high lactose, protein, vitamins, mineral & water content. Satisfies thirst of the baby.
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Natural contraception due to lactational amenorrhoea. Helps in uterine involution as oxytocin produced for milk production also contracts the uterus & prevents PPH. Incidence of breast cancer, ovarian cancer & osteoporosis is decreased. Decreases mother workload by saving time & energy. Burning off unwanted fat & thus useful for cosmetic purpose.
To society

Higher child survival decreases Healthcare load by preventing illness & allergies.

Helps in population control by natural contraception.

Conclusion

Human milk, in addition to its numerous nutrients that make it an ideal food source for the growing term infant, is a bioactive fluid that evolves from colostrum to mature milk as the infant matures. This bioactive fluid contains numerous factors & live cells that, in concert, promote the growth & well - being of the breastfeeding infant. Oliver Wendell Holmes said it best when he stated, A pair of substantial mammary glands has the advantage over the two hemispheres of the most learned professors brain, in the art of compounding a nutritious fluid for infants. With the ever - expanding knowledge resulting from current research, commercial formula clearly cannot replicate all of the valuable properties that are inherent in human milk.

Infants development is influenced by genetic factors, environment & nutrition. Good nutrition & healthy environment helps in normal development, while in under - nourished babies development can be delayed. Good nutrition also helps in proper development of brain & its functional aspect. There is no reason why an infant getting positive emotional support & protective environment should not develop normally.
Genetic factors

A)

63
Growth & development Growth - It is increase in size or mass of tissues which occurs due to

B) 1)

multiplication of cells leading to quantitative or physical maturation.

Physical Development (growth)

Genetic makeup (genotype) Physical expression (phenotype) parenteral characteristics Race Sex Biorhythm & maturation Genetic disorders (anomalies like trisomy21, trisomy 13, turner syndrome) Genetic mutations like metabolic defects (e.g. galactosemia, mucopolysaccharoidoses)
Environmental factors Prenatal causes

Basically, as a child grows it will have a height, a weight, head circumference, etc. With each of these measurements, there is a normal range of growth & then an abnormal deviance from this. If a child is under growing, it is referred to as failure to thrive. Development - It is maturation of functions or qualitative growth leading to mental maturation. It is dependent upon maturation & myelination of the nervous system.
Physiological development

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The key is to check that the child has reached the appropriate milestones for its age. This can be assessed from just watching the child & getting them to do stuff.
Factors affecting growth & development

Maternal malnutrition is related to IUGR &LBW babies. Maternal infections like TORCHS, chicken pox, syphilis & HIV. Maternal medications thalidomide leads to phocomelia Maternal irradiation during pregnancy causes severe fetal damage & anomalies. Maternal stress adversely affects the foetus. Maternal endocrinal diseases like DM leads to LGA babies & other congenital anomalies. Placental & uterine disorders like insufficiency, polyhydramnios, APH can adversely affect the foetus. Multiple pregnancies is associated with increased morbidity & mortality.

2)

Postnatal causes

Neonatal hypoxia leads to brain damage. SGA babies have grave prognosis than preterm. Availability of good nutrition, breast feeding Age of mother as maternal age advances there is greater incidence of anomalies like Downs syndrome. Age of father as paternal age advances it is associated with achondropoasia, craniostenosis, osteogenesis imperfecta. Physical factors like climate & pollution Biological factors infections lower the growth velocity. Exercise Accidents Emotional factors mother infant bonding, mother child interaction, anxiety & insecurity affect growth.

???? ???????? ??? (factors enhancing body elements) ???? ???? ??? : ?????? ???????? :???? ????????, ????????????!! ?. ?? 6/12 ???? ??? growth occurs as time passes. ?????? ???????? natural instinct of growing/genetic coding for growth. ???? ???????? nutritional factors like maternal nutrition, breast feeding & good weaning practices, supplementary feeding. ?????? physical & biological factors. ?? ?????? ??? ???? ???? ?????? ???? ????, ???? ?????? ???? ?, ?????? ?????? : ??? ?????????????????, ???? ???????, ? Laws of growth & development

4) Different tissues grow at different rates. Somatic growth very fast in first 2 - 3 yrs of life & then slows. Second spurt occurs in adolescence. It is maximum in later pregnancy & in first Brain growth two years of life. Almost 90% is completed at two years of age. Gonadal growth Noted around puberty. Lymphoid growth Especially tonsils, lymph nodes growth is prominent at mid - childhood (4 8yrs) as they act as organs of immunity in children. 5) Development is related to maturation of nervous system. 6) Certain primitive reflexes like grasp reflex & walking reflexes must be lost before achievement of corresponding voluntary movements. e.g. reflexes like asymmetric tonic neck reflex should be lost before voluntary movements like rolling over can be achieved. 7) Generalized mass activity of infants is replaced by specific responses e.g. on seeing a toy an infant shows interest by moving arms, legs & trunk, while older child merely smiles & opts for the object. 8) Delay in achieving single milestone is called isolated delay & it is of not much significance. 9) Global delay or gross development delay is highly pathological. 10) In case of preterm babies corrected age (conceptional age) = chronological age period of prematurity, should be considered up to infancy.
Stages of growth

1) 2) 3)

It is a continuous & orderly process. In each individual it has a unique pattern. General pattern is cephalocaudal i.e. head control is achieved first which is followed by ability to grasp, crawl, sit, stand, walk etc.

1) 2) 3)
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Prenatal Ovum Embryo Foetus Perinatal Postnatal Newborn

0 14 days 14 days to 9 wks 9 wks until birth. 28 wks of gestation to 7 days after birth.

first 4 wks (28) days

First 7 days early neonate Infancy first year of life Toddler 1 3 yrs Pre - school 3 6 yrs School age 6 to 10 yrs (girls) 6 to 12 yrs (boys) Adolescence Prepubescent 10 12 yrs (girls) 12 14 yrs (boys) Pubescent 12 - 14 yrs (girls) 14 16 yrs (boys) Post pubescent 14 18 yrs (girls) 16 20 yrs (boys)

2 yr quadriples the BW (12) 3 yr five times the BW (15) 5 yr BW * 6 (18) 10 yrs BW *10 (30) Newborn loses about 10% of birth wt. in first few days of life due to loss of edema & fluid. Regaining of wt. starts by 10th day of life.25 30 gm/day for 1st 3 mts. then, 400gm/mth up to 1 year of age.
Formula for calculating wt.

Importance of study of growth

It is an indicator of general indicator of general health & nutrition 2) Screening in public health 3) Clinically, early diagnosis can be made of moderate to severe mental disorders, cerebral palsy, hearing defects, neurological disorders, congenital anomalies like dislocations etc., birth trauma like fractures, dislocations. Assessment of growth it can be assessed by following means, 1) Anthropometry i.e. body measurements 2) Skeletal maturation 3) Growth charts 4) Percentile charts 5) Growth velocity 6) Predicted ht. in child based on mid parenteral height (MPH) 1) Anthropometry it includes height, weight, head circumference, chest circumference & mid arm circumference (MAC)
a) Weight

1)

At birth 2.5 1 to 6 yrs > To 12 yrs Up to 1 yr

b) Height

3.5 kg age * 2 + 8 age 3 or age 7/2 5 age in mts. + 9/2

Length for babies up to 2 yrs with infantometer Above 2 yrs height is measured by stadiometer. Formulae for calculating height After 2 yrs (2 12) yrs = age + 77 Birth length doubles by 4 yrs (100) Birth length triples by 12 yrs (149) Thereafter 5cm/yr up to 10 yrs. At birth 50 cm 1 yr 75 cm 2 yr 87 cm 3 yr 95 cm 4 yr 100 cm 12 yr 150 cm
Head circumference

It should be recorded with child unclothed. In neonates & infants detectometer (beam type) In older children spring machines or bathroom scales. Electronic scales or dial weight machines. At birth 2.5 3.5 kg 5 mts double of birthweight (6) 1 yr triple of birthweight (9)
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c)

It is a very important measurement in infants & children. It is measured with help of non stretchable, plastic tape encircling the prominent areas of forehead & occiput. Normal at birth 33 35 cm. Then increases 2 cm/month for first 3 mts. then 1cm/mth for next 3mts. then 0.5 cm/month for next 6 mts.

Birth 1yr 2yr 5yrs 10 yrs 12 yrs Up to 1 yr

d)

35cm 45cm 48cm 49cm 50cm 52cm. length in cm /2 + 9.5 (+/ - 2.5cm)

Chest circumference

care. They are useful for growth monitoring. Definition it is a visible graphical display of childs physical growth & development useful to monitor growth. The wt. measurements of a child are plotted on the growth chart & any deviation from the normal pattern can be visualized & interpreted. An upward curve in road to health is desirable. A flat curve & downward curve is not desirable. 1) 3) WHO charts ICDS charts 2) Govt. of India & IAP charts 4) UNICEF rainbow charts

It is measured at the level of nipples midway between inspiration & expiration. It is lower than head circumference at birth. Equals with head circumference at 1 yr of age. Then it exceeds the head circumference.
Mid arm circumference

Types of growth charts

Uses of growth charts

e)

2)

It is measured with help of non stretchable plastic tape, midway between the olecranon process & the acromion. It is constant between 1 4 yrs of age (about 13 to 17 cm) in healthy children.
Skeletal maturation

1) 2) 3) 4) 5)
4)

3)

In full term newborn babies, five ossification centers namely lower end of femur, upper end of tibia & three tarsal bones talus, calcaneus, cuboid appear. Head of humerus is present by 1 month. Head of femur by 4 6 mts. Carpal bones viz. capitates & hamate at 5 - 6 mt. The ossification centers appear first on left side of the body & then on the right side of the body. Bone age is delayed in hypopituitarism, hypothyroidism, severe malnutrition & constitutional delay It is advanced in precocious puberty.
Growth charts

Growth monitoring Diagnostic tool to identify high risk children, malnutrition. Education tool with the help of visual/color charts even mother can be educated to monitor growth. Planning & policy making by grading malnutrition it is possible to make a plan in relation to child health Other information identification, birth date, weight, immunization history, H/O sickness etc. are available.
Percentile charts

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These were first designed by David Morley. These are also known as road to health charts or passport to child health

When the anthropometric measurements of a large number of child populations of normal health are arranged in ascending order, we will get a bell shaped curve. The curve will be symmetrical on both sides & most of the observations will fall around the centre of the curve. This is called the Gaussian Distribution or bell shaped curve. Median is 50% value (average/mean) (standard value) SD is the degree of dispersion of the observations away from the mean. Median indicates that 50% of observations lie above & 50% lie below this point. 68.3% (app.2/3) of observations lie within 1 SD.

95.4% of observations lie within 2 SD around mean. Values beyond 2 SD are unusual. 99.7% fall beyond 3SD Allowable normal range of variation in observations is conventionally taken between 3rd & 97th percentile curve or mean +/ - 2 SD. 1 SD = observations between 16th (1 SD below mean) & 84th (1 SD above mean) percentile.
5) Growth velocity

5) 6)

Trivandrum developmental screening test (TDSC) Developmental observation card (DOC)

Developmental quotient (DQ) = developmental age/chronological age 100

Developmental age is the average of the motor & mental performances. In premature babies corrected age should be used. The story of transformation of a single cell in the womb (few micrometers) to a newborn that is 50 centimeters long, weighing around 2.5 kg (or more) is a very fascinating one. Development after the baby is born is another captivating journey that all children traverse to become an adult. This development is not only physical but also includes growth of these elements fine motor, language, cognitive & social. Milestones are changes in specific physical & mental abilities (such as walking & understanding language) that mark the end of one developmental period & the beginning of another. For stage theories, milestones indicate a stage transition. However, there is considerable variation in the achievement of milestones, even between children with developmental trajectories within the normal range. It is all very challenging since the child has to learn to move, sit & stand against gravity. He has to accustom his eyes to look & recognize objects, parents & everything in immediate environment & then he has to learn fine functions like holding, writing & eating etc. It signifies the control of body. Newborn - Limbs flexed - Symmetrical posture - Head lag on pulling the child up to the sitting position 6 - 8 weeks - Whilst lying on stomach, raises head 45 degrees 6 - 8 months - Sits without support, with a round back at 6 months & with a straight back at 8 months

Physical development of newly - born

It is the weight gain or height gain over a unit period of time. It is better indicator of growth. Wt. velocity 6 kg in first year. 1 kg/yr in pre - school child 2 kg/yr up to puberty. Height velocity 25 cm in first year 12.5 cm in second year 6 cm/yr till puberty.
MPH

6)

MPH (cm) for boys = (paternal ht. + maternal ht.)/2 +13 MPH (cm) for girls = (paternal ht. + maternal ht.)/2 - 13

Assessment of development

Largely based on works by Arnold Gessel. 1) Nancey Baley scale of development it measures motor & mental maturation. 2) Denver development screening test (DDST) gross motor, fine motor, social & linguistic 3) The Woodside system refers to social, language, vision, fine motor & gross motor areas. Developmental assessment can be done by any of the following set of tests 1) The Denver developmental screening test (DDST) 2) Bayley scale of infant development 3) Gessel development schedule (GDS) 4) Baroda developmental screening test (BDST)
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Gross motor

8 - 9 months - Crawling 10 months - Walks around with support from furniture 12 months - Walks unsteadily; broad - base gait 15 months - Walks steadily 18 months creeps upstairs & downstairs 2 yrs climbing stairs, running walks backwards 3 yrs rides tricycle 4 yrs goes downstairs, skips on one foot 6 yrs skips on both feet

4 years - Able to draw a square 5 years - Able to draw a triangle or multiplication sign 6 years - copies a hexagon/diamond 7 yrs - copies a kite 8 yrs - Copies a double lined cross 9 yrs copies a cylinder 11 yrs copies a cube.

Speech, language & hearing Newborn - Startles at loud noises

Fine motor & vision This includes eye coordination, hand eye coordination, hand mouth coordination & hand skills.

Newborn - Follows face in midline (but does not turn head) 6 weeks - Fix & follow - follows moving object by turning head 12 wks grasp reflex disappears, watch movement of own hands (hand regard) 4 months - Reaches for objects e.g. toys 6 months - Transfers objects from one to the other - Palmar grasp - grips object in palm 10 months - Pincer grip - can grip objects between a single finger & thumb 13 months can turn 2 pages of book 14 months - Scribbles with a pencil on a piece of paper 15 months can drink with a cup 18 months - Tower of 3 cubic building blocks, 2 years - Tower of 6 blocks, can draw horizontal or vertical lines Handedness is established at around 2 yrs. 2 years - Tower of eight building blocks OR - Train with four bricks - L - shape with the long side on the floor 3 years can build a tower of 9 blocks, Able to draw a circle, can dress & undress himself 4 years - Steps made from building blocks (after demonstration) - Able to draw a cross/rectangle
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1 month responds to sound of bell/rattle 3 months - Vocalizes alone, when spoken too, laughs, cooing (aah - aah) 6 months babbling da da ma ma. 7 months - Turns to soft sounds out of sight 9 months responds to name. 10 months speaks one word with meaning. 12 months - 2 to 3 words other than dada/mama 15 to 18 months child jargon. 18 months - 10 words - Can point to four parts of the body 20 - 24 months - Uses two or more words to make a simple phrase. 2 - 3 years - knows age & sex, Talks constantly in 3 - 4 word sentences. 4 years can tell a story, can tell experience of recent events. 5 years can speak atleast 10 word sentence. Names atleast 4 colors. 6 years knows right from left. 4 wks looks eagerly at face of mother or examiner 8 weeks social smile, Smiles responsively 3 months recognizes mother 6 months smiles at mirror image, imitation. 8 months - Separation anxiety, puts food in mouth, responds to no.

Social

10 months - Waves bye - bye, plays peek - a - boo. 12 months pulls clothes to attract mother 18 months - Holds a spoon & gets food safely to mouth Symbolic play, mimics others. Toilet training begins. 2 years - Dry by day wears simple garments/shoes/socks.. 3 years - Interactive play - Takes turns. 4 years plays with other children 5 years domestic plays, dresses without supervision, imaginative plays with doll.

5) 6)

Good enough draw a man test for Indian children Piagets theory of cognitive function IQ test is generally done in dyslexia or suspected MR. The child is asked to draw a man. The basic age of three years is required for this test

Draw a man test

Following important milestones should be achieved at age limits indicated below

Social smile Head holding Sitting with support Sitting without support Standing Walking

2 months 3 4 months 7 8 months 9 months 1 year 1 year.

Assessment of intelligence

It is the ability to know, understand & reason properly. Intelligence learning is not teaching or reading at early period but is motivating the child to find pleasure in learning, learn how to learn. Intelligence test can be employed in children above 3 yrs of age. These tests include several brain functions including hearing, vision, memory, receptive capacity & ability of expression through language. IQ above 85 is considered normal. Intelligence tests commonly used are Stanford Binet intelligence scale Binet Kamat test Wechsler intelligence scale for children (WISC) Malin intelligence scale for children (MISC)
197

Intelligence quotient (IQ) mental age/chronological age 100

1) 2) 3) 4)

Overview of motor, speech, vision & hearing development Developmental Milestones Age Motor Speech Vision & hearing Additional Notes

46 weeks Smiles at parent 68 weeks Vocalizes 1220 weeks

3 months

Prone : head held up for prolonged periods. No grasp reflex Holds head steady. Goes for objects & gets them. Objects taken to mouth Enjoys vocal play

Makes vowel noises

Hand regard : following Serves to practice the hand with the eyes emerging visual skills Also observed in blind children. Follows dangling toy Squeals with delight from side to side. appropriately. Turns head round Discriminates smile. to sound

5 months

198

6 months

Double syllable Localizes sound sounds such as 45 cm lateral to mumum & dada either ear

May show stranger shyness

Transfers objects from one hand to the other. Pulls self up to sit & sits erect with supports. Rolls over prone to supine. Palmar grasp of cube 910 months Wiggles & crawls. Sits unsupported. Picks up objects with pincer grasp 1 year

Babbles tunefully

Looks for toys dropped

Apprehensive about strangers

Stands holding furniture. Babbles 2 or 3 Stands alone for a words repeatedly second or two, then collapses with a bump

Drops toys & Cooperates with watches where they go dressing, waves goodbye, understands simple commands

18 months

Can walk alone. Picks up Jargon. toy without falling over. Many Gets up/down stairs intelligible words holding onto rail. Begins to jump with both feet. Can build a tower of 3 or 4 cubes & throw a ball Joins 23 words in sentences Parallel play. Dry by day

Demands constant mothering. Drinks from a cup with both hands. Feeds self with a spoon. Most children with autism are diagnosed at this age.

2 years

3 years

Able to run. Walks up & down stairs 2 feet per step. Builds tower of 6 cubes Goes up stairs 1 - foot per step & downstairs 2 feet per step. Copies circle, imitates cross & draws man on request. Builds tower of 9 cubes Constantly asks questions. Speaks in sentences.

Cooperative play. Undresses with assistance. Imaginary companions

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4 years

Goes down stairs one foot per step, skips on one foot. Imitates gate with cubes, copies a cross Copies a diamond. Knows right from left & number of fingers

Dresses & undresses with assistance. Attends to own toilet needs

6 years

Questioning at its height. Many infantile substitutions in speech Fluent speech

Physical specifications Age Average Length/height (cm) 14 months 48 months

Length growth

Average weight

Weight gain

Respiration Normal Heart Rate body rate per min. temp. pulse/ min.

Visual acuity (Snellen chart)

5070 cm (2028 in) 7075 cm (2830 in)

48 kg (8.818 lb) (doubling birth weight)

100200 g per week 500 g per month

30 to 40

35.7 37.5C 25 to 50

2.5 cm (0.98 in) per month 1.3 cm (0.51 in) per month

812 months

Approx.1.5 times birth length by 1st birthday 22 to 40

500 g per month

20 to 45

35.7 37.5 C (96 100 F)

20/100

12-24 months 2 years

8090 cm (3135 in) 8595 cm (3337 in) 1 kg per year 20 to 35

58 cm (2.03.1 in) per year 713 cm (2.85.1 in) per year 1215 kg (2633 lb) about 4 times birth weight 1317 kg (2937 lb) 1.42.3 kg per year 20 to 30

9.6 kg (21 lb) Nearly triple the birth wt. by 1st birthday 913 kg (2029 lb) 130250 g per month 80 to 110

20/60

3 years

35 37 C

90 to 110

20/40

4 years

95100 cm 58 cm (3739 in) (2.03.1 in) Nearly double per year birth length 101.6114 cm 56.5 cm (40.045 in) (2.02.6 in) per year 14.517 kg (3237 lb)

1.82.3 kg per year

2030

36.6 90 to 37.4C 110

20/30

200

5 years

105115 cm (4145 in)

1721 kg (3746 lb)

1.82.3 kg per year

2030

90 to 110

20/20

> 5 years 105120 cm

(4147 in)

56.5 cm (2.02.6 in) per year 57 cm (2.02.8 in) per year

1722 kg (3749 lb)

2 kg per year

Specifications sorted by reached age 14 months Physical

Upper body parts are more active : clasps hands above face, waves arms about, reaches for objects.

48 months Physical

Head & chest circumference are nearly equal to the part of the abdomen. Head circumference increases approximately 2 cm per month until two months, then increases 1.5 cm per month until four months. Increases are an important indication of continued brain growth. Continues to breathe using abdominal muscles. Posterior fontanel closes by the second month. Anterior fontanel closes to approximately 1.3 cm. Skin remains sensitive & easily irritated. Legs may appear slightly bowed. Cries with tears. Eyes begin moving together in unison (binocular vision). Rooting & sucking reflexes are well developed. Swallowing reflex & tongue movements are still immature; continued drooling & inability to move food to the back of the mouth. Grasp reflex gradually disappears. Landau reflex appears near the middle of this period; when baby is held in a prone (face down) position, the head is held upright & legs are fully extended. Grasps with entire hand; strength insufficient to hold items. Holds hands in an open or semi - open position. Muscle strength & control improving; early movements are large & jerky; gradually become smoother & more purposeful. Raises head & upper body on arms when in a prone position. Turns head side to side when in a supine (face up) position; near the end of this period can hold head up & in line with the body.
201

Motor development

Head & chest circumferences are basically equal. Head circumference increases approximately 1 cm per month until six to seven months, then 0.5 cm per month; head circumference should continue to increase steadily, indicating healthy, ongoing brain growth. Breathing is abdominal; respiration rate depending on activity; rate & patterns vary from infant to infant. Teeth may begin to appear, with upper & lower incisors coming in first. Gums may become red & swollen, accompanied by increased drooling, chewing, biting & mouthing of objects. Legs may appear bowed; bowing gradually disappears as infant grows older. Fat rolls (Baby Fat) appear on thighs, upper arms & neck. True eye color is established. Reflexive behaviors are changing : Blinking reflex is well established Sucking reflex becomes voluntary Moro reflex disappears When lowered suddenly, infant throws out arms as a protective measure. Swallowing reflex appears & allows infant to move solid foods from front of mouth to the back for swallowing. Picks up objects using finger & thumb (pincer grip). Reaches for objects with both arms simultaneously; later reaches with one hand or the other. Transfers objects from one hand to the other; grasps object using entire hand (palmar grasp). Handles, shakes & pounds objects; puts everything in mouth. Able to hold bottle.

Motor development

Sits alone without support, holding head erect, back straightened & arms propped forward for support Pulls self into a crawling position by raising up on arms & drawing knees up beneath the body; rocks back & forth, but generally does not move forward. Lifts head when placed on back. Can roll over from back or stomach position. May accidentally begin scooting backwards when placed on stomach; soon will begin to crawl forward. Looks for fallen objects by 7 months Plays peek - a - boo games Cannot understand no or danger

812 Months Physical

Respiration rates vary with activity Environmental conditions, weather, activity & clothing still affect variations in body temperature. Head & chest circumference remain equal. Continues to use abdominal muscles for breathing. Anterior fontanel begins to close. More teeth appear, often in the order of 2 lower incisors then 2 upper incisors followed by four more incisors & two lower molars but some babies may still be waiting for their first. Arm & hands are more developed than feet & legs (cephalocaudal development); hands appear large in proportion to other body parts. Legs may continue to appear bowed. Baby Fat continues to appear on thighs, upper arms & neck. Feet appear flat as arch has not yet fully developed. Both eyes work in unison (true binocular coordination). Can see distant objects (4 to 6 mt. or 13 to 20 ft. away) & points at them.

Reaches with one hand leading to grasp an offered object or toy. Manipulates objects, transferring them from one hand to the other. Explores new objects by poking with one finger. Uses deliberate pincer grasp to pick up small objects, toys & finger foods. Stacks objects; also places objects inside one another. Releases objects or toys by dropping or throwing; cannot intentionally put an object down. Beginning to pull self to a standing position. Beginning to stand alone, leaning on furniture for support; moves around obstacles by side - stepping. Has good balance when sitting; can shift positions without falling. Creeps on hands & knees; crawls up & down stairs. Walks with adult support, holding onto adults hand; may begin to walk alone. Watches people, objects & activities in the immediate environment. Shows awareness of distant objects (4 to 6 mt. or 13 to 20 ft. away) by pointing at them. Responds to hearing tests (voice localization); however, loses interest quickly and, therefore, may be difficult to test informally. Follows simple instructions. Reaches for toys that are out of reach but visible Recognizes objects in reverse Drops thing intentionally & repeats & watches object Imitates activities like playing drum

Toddlers (1224 months) Physical

Motor development
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Weight is now approximately 3 times the childs birth weight. Respiration rate varies with emotional state & activity.

Rate of growth slows Head size increases slowly; grows approximately 1.3 cm every six months; anterior fontanel is nearly closed at eighteen months as bones of the skull thicken. Chest circumference is larger than head circumference. Rapid eruption of teeth; six to ten new teeth will appear. Legs may still appear bowed. Toddler will begin to lose the Baby Fat once he/she begins walking. Body shape changes; takes on more adult - like appearance; still appears top - heavy; abdomen protrudes, back is swayed. Crawls skillfully & quickly. Stands alone with feet spread apart, legs stiffened & arms extended for support. Gets to feet unaided. Most children walk unassisted near the end of this period; falls often; not always able to maneuver around obstacles, such as furniture or toys. Uses furniture to lower self to floor; collapses backwards into a sitting position or falls forward on hands & then sits. Enjoys pushing or pulling toys while walking. Repeatedly picks up objects & throws them; direction becomes more deliberate. Attempts to run; has difficulty stopping & usually just drops to the floor. Crawls up stairs on all fours; goes down stairs in same position. Sits in a small chair. Carries toys from place to place. Enjoys crayons & markers for scribbling; uses whole - arm movement. Helps feed self; enjoys holding spoon (often upside down) & drinking from a glass or cup; not always accurate in getting utensils into mouth; frequent spills should be expected.
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Helps turn pages in book. Stacks two to six objects per day. Enjoys object - hiding activities Early in this period, the child always searches in the same location for a hidden object (if the child has watched the hiding of an object). Later, the child will search in several locations. Passes toy to other hand when offered a second object (referred to as crossing the midline - an important neurological development). Manages three to four objects by setting an object aside (on lap or floor) when presented with a new toy. Puts toys in mouth less often. Enjoys looking at picture books. Demonstrates understanding of functional relationships (objects that belong together) : Puts spoon in bowl & then uses spoon as if eating; places teacup on saucer & sips from cup; tries to make doll stand up. Shows or offers toy to another person to look at. Names many everyday objects. Shows increasing understanding of spatial & form discrimination : puts all pegs in a pegboard; places three geometric shapes in large form board or puzzle. Places several small items (blocks, clothespins, cereal pieces) in a container or bottle & then dumps them out. Tries to make mechanical objects work after watching someone else do so. Responds with some facial movement, but cannot truly imitate facial expression. Most children with autism are diagnosed at this age. Produces considerable jargon : puts words & sounds together into speech - like (inflected) patterns. Holophrastic speech : uses one word to convey an entire

Cognitive development

Motor development

Language

thought; meaning depends on the inflection (me may be used to request more cookies or a desire to feed self). Later; produces two - word phrases to express a complete thought (telegraphic speech) : More cookie, Daddy bye - bye. Follows simple directions, Give Daddy the cup. When asked, will point to familiar persons, animals & toys. Identifies three body parts if someone names them : Show me your nose (toe, ear). Indicates a few desired objects & activities by name : Bye bye, cookie; verbal request is often accompanied by an insistent gesture. Responds to simple questions with yes or no & appropriate head movement. Speech is 25 to 50 percent intelligible during this period. Locates familiar objects on request (if child knows location of objects). Acquires & uses five to fifty words; typically these are words that refer to animals, food & toys. Uses gestures, such as pointing or pulling, to direct adult attention. Enjoys rhymes & songs; tries to join in. Seems aware of reciprocal (back & forth) aspects of conversational exchanges; some turn - taking in other kinds of vocal exchanges, such as making & imitating sounds. Less wary of strangers. Helps pick up & put away toys. Plays by themselves Enjoys being held & read to. Often imitates adult actions in play. Enjoys adult attention; likes to know that an adult is near; gives hugs & kisses. Recognizes self in mirror. Enjoys the companionship of other children, but does not play
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cooperatively. Beginning to assert independence; often refuses to cooperate with daily routines that once were enjoyable; resists getting dressed, putting on shoes, eating, taking a bath; wants to try doing things without help. May have a tantrum when things go wrong or if overly tired or frustrated. Exceedingly curious about people & surroundings; toddlers need to be watched carefully to prevent them from getting into unsafe situations. Autonomy vs. Shame & Doubt (will) Psychosocial stimulation is vital during the toddler years. Play begins to become interactive. Toddlers begin to learn & exhibit independence, but ironically they enjoy sharing this discovery with others. Another important advancement is active social play with adults including mirroring & repeating. Songs, rhymes & finger plays (e.g. incy wincy spider, little teapot, etc.) are a great way to encourage & stimulate this area of development.

Psychological

2 year old Physical

Social

Posture is more erect; abdomen still large & protruding, back swayed, because abdominal muscles are not yet fully developed. Respirations are slow & regular Body temperature continues to fluctuate with activity, emotional state & environment. Brain reaches about 80 percent of its adult size. 15 baby teeth almost finished growing out Can walk around obstacles & walk more erect Squats for long periods while playing. Climbs stairs unassisted (but not with alternating feet).

Motor development

Balances on one foot (for a few moments), jumps up & down, but may fall. Often achieves toilet training during this year (depending on childs physical & neurological development) although accidents should still be expected; the child will indicate readiness for toilet training. Throws large ball underhand without losing balance. Holds cup or glass (be sure it is unbreakable) in one hand. Unbuttons large buttons; unzips large zippers. Opens doors by turning doorknobs. Grasps large crayon with fist; scribbles enthusiastically on large paper. Climbs up on chair, turns around & sits down. Enjoys pouring & filling activities - sand, water, styrofoam peanuts. Stacks four to six objects on top of one another. Uses feet to propel wheeled riding toys. Eyehand movements better coordinated; can put objects together, take them apart; fit large pegs into pegboard. Begins to use objects for purposes other than intended (may push a block around as a boat). Does simple classification tasks based on one dimension (separates toy dinosaurs from toy cars). Stares for long moments; seems fascinated by, or engrossed in, figuring out a situation : where the tennis ball has rolled, where the dog has gone, what has caused a particular noise. Attends to self - selected activities for longer periods of time. Discovering cause & effect : squeezing the cat makes her scratch. Knows where familiar persons should be; notes their absence; finds a hidden object by looking in last hiding place first. (This is what Piaget termed object permanence, which usually occurs during the sensorimotor stage of Piagets childhood theory of
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cognitive development) Names objects in picture books; may pretend to pick something off the page & taste or smell it. Recognizes & expresses pain & its location. Is expected to use magical thinking, such as believing that a toy bear is a real bear. Enjoys being read to if allowed to participate by pointing, making relevant noises, turning pages. Realizes that language is effective for getting others to respond to needs & preferences. Uses fifty to three hundred different words; vocabulary continuously increasing. Has broken the linguistic code; in other words, much of a two - year - olds talk has meaning to him or her. Receptive language is more developed than expressive language; most two - year olds understand significantly more than they can talk about. Utters three - & four - word statements; uses conventional word order to form more complete sentences. Refers to self as me or sometimes I rather than by name : Me go bye - bye; has no trouble verbalizing mine. Expresses negative statements by tacking on a negative word such as no or not : Not more milk. Repeatedly asks, Whats that? Uses some plurals; tells about objects & events not immediately present (this is both a cognitive & linguistic advance). Some stammering & other dysfluencies are common. Speech is as much as 65 to 70 percent intelligible. Is able to verbalize needs. Shows signs of empathy & caring : comforts another child if hurt or frightened; appears to sometimes be overly affectionate in offering hugs & kisses to children

Language

Cognitive

Social & emotional

Continues to use physical aggression if frustrated or angry (for some children, this is more exaggerated than for others); Physical aggression usually lessens as verbal skills improve. Temper tantrums likely to peak during this year; cannot be reasoned with while tantrum is in progress. Impatient; finds it difficult to wait or take turns. Enjoys helping with household chores; imitates everyday activities : may try to toilet a stuffed animal, feed a doll. Bossy with parents & caregivers; orders them around, makes demands, expects immediate compliance from adults. Watches & imitates the play of other children, but seldom interacts directly; plays near others, often choosing similar toys & activities (parallel play); solitary play is often simple & repetitive. Offers toys to other children, but is usually possessive of playthings; still tends to hoard toys. Making choices is difficult; wants it both ways. Often defiant; shouting no becomes automatic. Ritualistic; wants everything just so; routines carried out exactly as before; belongings placed where they belong.

baby teeth stage over. Needs to consume approximately 6, 300 J (1, 500 calories) daily. Walks up & down stairs unassisted, using alternating feet; may jump from bottom step, landing on both feet. Can walk on one foot, balance momentarily. Can kick big ball - shaped objects. Needs minimal assistance eating. Jumps on the spot. Pedals a small tricycle. Throws a ball overhand; aim & distance are limited. Catches a large bounced ball with both arms extended. Enjoys swinging on a swing (not too high or too fast). Shows improved control of crayons or markers; uses vertical, horizontal & circular strokes. Holds crayon or marker between first two fingers & thumb (tripod grasp), not in a fist as earlier. Can turn pages of a book one at a time Enjoys building with blocks. Builds a tower of eight or more blocks. Enjoys playing with clay; pounds, rolls & squeezes it. May begin to show hand dominance. Carries a container of liquid, such as a cup of milk or bowl of water, without much spilling; pours liquid from pitcher into another container. Manipulates large buttons & zippers on clothing. Washes & dries hands; brushes own teeth, but not thoroughly. Usually achieves complete bladder control during this time. Listens attentively to age - appropriate stories. Makes relevant comments during stories, especially those that relate to home & family events. Likes to look at books & may pretend to read to others or

Motor development

3 year old Physical

Growth is steady though slower than in first two years. Adult height can be predicted from measurements of height at three years of age; males are approximately 53% of their adult height & females, 57%. Legs grow faster than arms, Circumference of head & chest is equal; head size is in better proportion to the body. Baby fat disappears as neck appears. Posture is more erect; abdomen no longer protrudes. Slightly knock - kneed. can jump from low step can stand up & walk around on tiptoes
206

Cognitive development

explain pictures. Enjoys stories with riddles, guessing & suspense. Speech is understandable most of the time. Produces expanded noun phrases : big, brown dog. Produces verbs with ing endings; uses - s to indicate more than one; often puts - s on already pluralized forms : geeses, mices. Indicates negatives by inserting no or not before a simple noun or verb phrase : Not baby. Answers What are you doing?, What is this? & Where? questions dealing with familiar objects & events.

Paints & draws with purpose; may have an idea in mind, but often has problems implementing it so calls the creation something else. Becomes more accurate at hitting nails & pegs with hammer. Threads small wooden beads on a string. Can run in a circle Can recognize that certain words sound similar Names eighteen to twenty uppercase letters. Writes several letters & sometimes their name. A few children are beginning to read simple books, such as alphabet books with only a few words per page & many pictures. Likes stories about how things grow & how things operate. Delights in wordplay, creating silly Language. Understands the concepts of tallest, biggest, same, & more; selects the picture that has the most houses or the biggest dogs. Rote counts to 20 or more. Understands the sequence of daily events : When we get up in the morning, we get dressed, have breakfast, brush our teeth & go to school. When looking at pictures can recognize & identify missing puzzle parts (of person, car & animal). Very good storytellers. Counts 1 to 7 objects out loud, but not always in order follows two to three step directions given individually or in a group May put the ed on the end of words such as I goed outside & I played. Uses the prepositions on, in, & under. Uses possessives consistently : hers, theirs, babys. Answers Whose?, Who?, Why? & How many? Produces elaborate sentence structures : The cat ran under

Cognitive

4 year old Physical Development

Head circumference is usually not measured after age three. Requires approximately 1, 700 calories daily. Hearing acuity can be assessed by childs correct usage of sounds & Language also, by the childs appropriate responses to questions & instructions. Walks a straight line (tape or chalk line on the floor). Hops on one foot. Pedals & steers a wheeled toy with confidence; turns corners, avoids obstacles & oncoming traffic. Climbs ladders, trees, playground equipment. Jumps over objects 12 to 15 cm (5 to 6 in) high; lands with both feet together. Runs, starts, stops & moves around obstacles with ease. Throws a ball overhand; distance & aim improving. Builds a tower with ten or more blocks. Forms shapes & objects out of clay : cookies, snakes, simple animals. Reproduces some shapes & letters. Holds a crayon or marker using a tripod grasp.
207

Motor Development

Language

the house before I could see what color it was. Speech is almost entirely intelligible. Begins to correctly use the past tense of verbs : Mommy closed the door, Daddy went to work. Refers to activities, events, objects & people that are not present. Changes tone of voice & sentence structure to adapt to listeners level of under - standing : To baby brother, Milk gone? To Mother, Did the baby drink all of his milk? States first & last name, gender, siblings names & sometimes own telephone number. Answers appropriately when asked what to do if tired, cold, or hungry. Recites & sings simple songs & rhymes. Outgoing; friendly; overly enthusiastic at times. Moods change rapidly & unpredictably; laughing one minute, crying the next; may throw tantrum over minor frustrations (a block structure that will not balance); sulk over being left out. Imaginary playmates or companions are common; holds conversations & shares strong emotions with this invisible friend. Boasts exaggerates & bends the truth with made - up stories or claims of boldness; tests the limits with bathroom talk. Cooperates with others; participates in group activities. Shows pride in accomplishments; seeks frequent adult approval. Often appears selfish; not always able to take turns or to understand taking turns under some conditions; tattles on other children. Insists on trying to do things independently, but may get so frustrated as to verge on tantrums when problems arise : paint that drips, paper airplane that will not fold right. Enjoys role - playing & make - believe activities. Relies (most of the time) on verbal rather than Physical aggression; may yell angrily rather than hit to make a point; threatens : You cant come to my birthday party
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Name - calling & taunting are often used as ways of excluding other children. Establishes close relationships with playmates; beginning to have best friends.

5 year old Physical

Head size is approximately that of an adults. May begin to lose baby (deciduous) teeth. Body is adult - like in proportion. Requires approximately 7, 500 J (1, 800 calories) daily Visual tracking & binocular vision are well developed. Walks backwards, toe to heel. Walks unassisted up & down stairs, alternating feet. May learn to turn somersaults (should be taught the right way in order to avoid injury). Can touch toes without flexing knees. Walks a balance beam. Learns to skip using alternative feet. Catches a ball thrown from 1 m (3.3 ft) away. Rides a tricycle or wheeled toy with speed & skillful steering; some children learning to ride bicycles, usually with training wheels. Jumps or hops forward ten times in a row without falling. Balances on either foot with good control for ten seconds. Builds three - dimensional structures with small cubes by copying from a picture or model. Reproduces many shapes & letters : square, triangle, A, I, O, U, C, H, L, T. Demonstrates fair control of pencil or marker; may begin to color within the lines. Cuts on the line with scissors (not perfectly). Hand dominance is fairly well established.

Social development

Motor development

Cognitive

Forms rectangle from two triangular cuts. Builds steps with set of small blocks. Understands concept of same shape, same size. Sorts objects on the basis of two dimensions, such as color & form. Sorts a variety of objects so that all things in the group have a single common feature (classification skill : all are food items or boats or animals). Understands the concepts of smallest & shortest; places objects in order from shortest to tallest, smallest to largest. Identifies objects with specified serial position : first, second, last. Rote counts to 20 & above; many children count to 100. Recognizes numerals from 1 to 10. Understands the concepts of less than : Which bowl has less water? Understands the terms dark, light & early : I got up early, before anyone else. It was still dark. Relates clock time to daily schedule : Time to turn on TV when the little hand points to 5. Some children can tell time on the hour : five oclock, two oclock. Knows what a calendar is for. Recognizes & identifies coins; beginning to count & save money. Many children know the alphabet & names of upper - & lowercase letters. Understands the concept of half; can say how many pieces an object has when its been cut in half. Asks innumerable questions : Why? What? Where? When? Eager to learn new things. Vocabulary of 1, 500 words plus.
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Tells a familiar story while looking at pictures in a book. Defines simple words by function : a ball is to bounce; a bed is to sleep in. Identifies & names four to eight colors. Recognizes the humor in simple jokes; makes up jokes & riddles. Produces sentences with five to seven words; much longer sentences are not unusual. States the name of own city or town, birthday & parents names. Answers telephone appropriately; calls person to phone or takes a brief message Speech is almost entirely intelligible. Uses would & could appropriately. Uses past tense of irregular verbs consistently : went, caught, swam. Uses past - tense inflection (- ed) appropriately to mark regular verbs : jumped, rained, washed. Enjoys & often has one or two focus friendships. Plays cooperatively (can lapse), is generous, takes turns, shares toys. Participates in group play & shared activities with other children; suggests imaginative & elaborate play ideas. Shows affection & caring towards others especially those below them or in pain Generally subservient to parent or caregiver requests. Needs comfort & reassurance from adults but is less open to comfort. Has better self - control over swings of emotions. Likes entertaining people & making them laugh. Boasts about accomplishments.

Social development

Language development

6 year old Physical

Weight gains reflect significant increases in muscle mass. Heart rate & respiratory rates are close to adults. Body may appear lanky as through period of rapid growth. Baby teeth beginning to be replaced by permanent ones, starting with the two upper front teeth 20/20 eyesight; if below 20/40 should see a professional. The most common vision problem during middle childhood is myopia, or nearsightedness. (Berk, 2007). Uses 6, 700 J to 7, 100 J (1, 600 to 1, 700 calories) a day. Gains greater control over large & fine motor skills; movements are more precise & deliberate, though some clumsiness persists. Enjoys vigorous running, jumping, climbing & throwing est. Has trouble staying still. Span of attention increases; works at tasks for longer periods of time, though Can concentrate effort but not always consistently. Understands time (today, tomorrow, yesterday) & simple motion (things go faster than others). Recognizes seasons & major activities done in the times. Has fun with problem solving & sorting activities like stacking, puzzles & mazes Enjoys the challenge of puzzles, counting & sorting activities, paper - & - pencil mazes & games that involve matching letters & words with pictures. Recognizes some words by sight; attempts to sound out words In some cases the child may be reading well. Functioning which facilitates learning to ride a bicycle, swim, swing a bat, or kick a ball. Making things is enjoyed. Reverses or confuse certain letters : b/d, p/g, g/q, t/f. Able to trace objects. Folds & cuts paper into simple shapes. Can Tie Laces, string (like shoes).
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Language

Motor development

Can identify right & left hands fairly consistently. Holds onto positive beliefs involving the unexplainable (magic or fantasy) Arrives at some understanding about death & dying; expresses fear that parents may die. Talks a lot. Loves telling jokes & riddles; often, the humor is far from subtle. Experiments with slang & profanity & finds it funny. Enthusiastic & inquisitive about surroundings & everyday events. Able to carry on adult - like conversations; asks many questions. Learns 5 to 10 words a day; vocabulary of 10, 00014, 000. Uses appropriate verb tenses, word order & sentence structure. Uses language rather than tantrums or physical aggression to express displeasure : Thats mine! Give it back, you dummy. Talks self through steps required in simple problem - solving situations (though the logic may be unclear to adults). Has mood swings towards primary caregiver depending on the day Friendship with parent is less depended on but still needs closeness & nurturing. Anxious to please; needs & seeks adult approval, reassurance & praise; may complain excessively about minor hurts to gain more attention. Often cant view the world from anothers point of view Self - perceived failure can make the child easily disappointed & frustrated. Cant handle things not going their own way Does not understand ethical behavior or moral standards especially when doing things that have not been given rules Understands when he or she has been thought to be bad; values are based on others enforced values.

Social & emotional

May be increasingly fearful of the unknown like things in the dark, noises & animals.

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All parents wish their children to be healthy & theres a great deal you can do to give your child the best start in life as well as good health in later years. The first few years are of vital importance, for this is the crucial time when the foundations for future good health are laid. Food & nutrients are the building blocks in a good diet, which help them to form strong teeth & bones, muscles & healthy tissues. A good diet can also help to protect against illness. A childs diet needs special care & planning - the requirements for energy & nutrients are high, but appetite is small & eating habits are likely to be finicky. The diet therefore needs to be : Made up of small frequent meals, Diet to be Nutrient & energy Dense - providing plenty of nutrients in small volume of food.
Particularly important nutrient include Iron - Iron deficiency is common in this age group as iron requirements

calcium) & can be synthesized through the action of sunlight on the skin. In winter & if your child is always covered, make sure that you include dietary sources of vitamin D, along with vitamin D in tablet or liquid form.

are high but dietary intake is often low, especially if little or no meat is eaten. Foods rich in Vitamin C such as orange or tomato with evening meal eaten at the same time help maximize iron absorption. Calcium - This is vital for the growth of bones & teeth. Requirements will be met as long as the child consumes enough milk & dairy products. Vitamin A, C, D - Vitamin A is needed for healthy skin & cell development & can be often be lacking in diets of this age group. Vitamin C is important for the immune system & growth. It also helps in the absorption of iron, especially iron from non - meat sources (non heme iron). Vitamin intakes are often low in children who eat little. Vitamin D is essential for calcium metabolism (breakdown of
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Key nutrients & dietary sources Nutrient Iron Important for Dietary sources

Needed to make red blood cells & carry oxygen to the body as part of hemoglobin the blood.

Calcium

Essential for strong bones & teeth, blood clotting & nerve cells.

Meat based (heme) sources - eggs, lamb, meat, liver & kidney. Plant (non heme) sources fortified cereals like cornflakes, bread, dried fruits, beans, pulses & green leafy vegetables (cabbage, spring onions, palak, methi, green beans) Non - Dairy based Fish with soft edible bones, dark leafy vegetables, sesame seeds (Til). Dairy based products-milk, yoghurt (dahi) cheese, paneer

Vitamin A Formation & maintenance of skin, hair &

membranes, needed for bone & teeth growth & help us see in the dark Vitamin C Essential for structure of bones, cartilages & muscles.
Vitamin D Aids in bone & tooth formation &

helps the heart & nervous system

Yellow & orange fruits & vegetables (peppers, tomatoes mango & apricots), dark leafy vegetables & dairy products Helps the immune system & the absorption of iron Citrus fruits, berries & vegetables (make sure you dont cook too soft) potatoes & fruit juice. Fishes like mackerel, Bombay duck & dairy products.

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Tasty snacks

Milk & dairy foods :

4 Major Food Groups

Yoghurt (dahi)

Cornflakes Popcorn Toast, Bun, Potato pattice Upma, Poha Pancakes (Made from rice flour & Gram flour (Chana Atta) Palak Puri, Thepla.

More substantial meals

Aim for 500-600 ml of milk each day. It will provide energy for growth & calcium for strong bones & teeth. Milk Cheese

Bread, other cereals & potatoes

Ragi porridge/cornflakes with milk Vermicelli cooked in milk Rice pudding, custard Rawa or Sago kheer Bread pudding Cheese on Bread Cubes of Cheese Cheese on Vegetables Soup with grated Cheese Paneer in curries Add fresh fruit to Yoghurt Yoghurt with Sugar or Honey Yoghurt made into Lassi drink / Fruit Lassi To serve as Kadhi

Starchy staples form an important part of anyones diet. They are also called as fillers. They provide energy, various nutrients & fibre. One can choose from variety of breads, cornflakes, maize, jowar, bajra, potatoes, yam (suran), rice, chapatti & rotlas.

Suitable foods are divided into Four Major Groups & a fifth Minor - or occasional group. If childs intake includes these groups it certain that all the important nutrients are provided.


3)

Chapatti or Stuffed Paratha with Paneer or Dal or Potato Pulav or Khichri with Yoghurt Noodles or rice mixed with shredded omelet & vegetables Chapattis or Rotlas with vegetables or dal. Omelet with bread or sandwiches. Omelet with bread or sandwiches.
Fruits & vegetable group

5th group the occasional foods group - It consists of

They contain lot of vitamins, minerals & fibre & also add variety to meals by adding coloring textures & flavors. Try & introduce lots of different types from early age. Stuffed parathas with vegetables Spinach cutlets or Vegetable cutlets. Theplas (Wheat flour mixed with Methi or Spinach) Give Carrot sticks, Apple slices, Banana slices, Cucumber Slices, Tomato Slices, or Pineapple Slices as snacks. Mix chopped or mashed vegetables with rice or Dal. Use fruits in puddings
4) Meat, fish & veg. alternatives

Sugar : A small amount of sugar as mild sweetening is fine with foods in MILK Group. Fatty & sugary foods : This group includes butter, ghee, oil sugar, biscuits, cakes, wafers, sweets, chocolates, ice cream, soft drinks & other sugary drinks. - These foods should not be given too often & when they are, only in small amounts. Too much will impair the intake of more nutritious foods from the other food groups & compromise the quality of diet. Children between this age group require around 25 gm of fat per day. When teeth are in constant contact with sugary foods & drinks, they will decay. Therefore avoid using foods like cakes, biscuits, chocolate & such foods as reward.
Possible Solutions

Some Common problems Problems

Food refusal

Protein is needed by young children to grow & develop. Meat, Fish, Eggs, Nut, Pulses, Beans, Lentils, Peas & Soya Granules are good sources of proteins. If you are vegetarian, give at least 2 portions of vegetable servings to ensure enough proteins & iron in the diet.
Meat & fish

Boiled Egg, omelet Sandwich made with shredded chicken Egg on toast Lentil soup Sprouts boiled & made into chat. Dal or lentil curry with chapatti or rice. Fish curry with rice Mince meat cutlets. Or meat soup VEG. ALTERNATIVES Dal khichri Lentil soup
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Structured meal pattern3 meals & 2 - 3 small nutritious snacks Offer variety of foods with some favorites Offer small portions & praise your child for eating even a little Do not force feed Family mealtimes Happy, relaxed environment Do not offer sweets or favorite foods as reward instead reward them with a trip to park, zoo or taking out to museum Refuses to Offer in small fun cup or through a colored straw drink milk Add milk or cream (malai) to foods Include milk - containing foods like kheer, porridge, custard, homemade ice cream & lassi. Try flavored milk or milkshakes. Refuses Try mixing vegetables in other foods to eat Include small amount of fruits or vegetables at

fruits & each mealtime to allow opportunity to try vegetables Children learn by example - if parents & other family members eat fruits & vegetable then they are more likely to do so. Blend fruit drinks or milk shakes added fruit To prepare kheer or porridge with added fruits Excessive Limit milk intake to 500 - 600 ml per day milk Give milk after meals or at snacks time drinking Use cup not bottle Offer milk in small cups

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The word weaning is derived from the word wenian which means to accustom. It is defined as the systematic introduction of suitable food at right time with addiction to mothers milk in order to provide nourishment to the infant. It is a gradual process of replacement of breast feeding by introduction to a wide range of non milk suitable food mainly semisolid foods. The baby is taken away gradually from the from the habit of sucking at the breast which is the second most step towards independent existence. The first step is cutting of the umbilical cord. Weaning the baby from the breast or the bottle starts from about 4 - 6 months for following reasons Breast milk provides essential nourishment up to 6 mt. of age hence most babies grow well on breast milk. By 6 mt. breast milk production is on its peak after which it starts to decrease in quantity. During 6 - 7 mt. gum hardening & tooth eruption takes place which is an indication for introducing semisolid food. Weight of the baby doubles at about 5 mt. of age From about 4 - 6 months old, baby needs more iron & other nutrients like Vitamin D & Vitamin C that milk alone cannot
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give. Hand & mouth coordination is established at about 5 - 6 mt. Head control is achieved at about 4 mt. of age. Hence baby can be fed in upright position. 8) Amylase enzyme appears in the gut which is necessary for digestion of starch. 9) Breast milk & cows milk is unable to provide enough energy & other nutrients to maintain growth velocity in infants after 4 mt. of age. 10) Late weaning leads to growth failure & malnutrition. Weaning is a transition from breast milk or formula milk to solid foods. It is divided into the following stages : Initial period - Babies are usually ready to start on solid foods between 4 - 6 months. 6 - 9 months. 9 - 12 months. 6) 7)
Initial period : From 4 - 6 months

1) 2) 3) 4) 5)

Baby should be still having 600ml of breast or infant formula milk daily. Starchy foods : Initially cereal is used such as baby rice or sago (sabudana). Cereal based gruel (khichidi, kanji) can be given. Mashed, potato, banana, carrot, sweet potato, yam (suran) can be given. Vegetables & fruits : soft cooked vegetables & fruits are suitable e.g. : apple, pear, mango & chickoo. Fruit juices & mashed seasonal fruits can be given to provide vit. C & provitamin A. Pulses provide protein, iron & B - complex. Non fibrous vegetables e.g. cauliflower, pureed spinach, lauki (bottle gourd, dudhi)
Remember

1)

The aim is to get the baby used to taking food from a spoon Start with teaspoonful (quantities will be small) & milk will

2) 3) 4)

still be major sources of nutrients) Foods should not be salted or sweetened. Dont force food on the baby - If the food doesnt seem to be wanted, wait & try again another day. To try the food after a milk feed or in the middle of one By this age the baby should be fed with most of the food cooked in the house. Gradually increase amount of food to give either before or after milk feed. Dairy products : Cows milk may be used to mix solids. Cheese may be given as finger foods. Introduce wheat based cereals - khichri (gruel of rice & pulses) sooji halwa / porridge nachni mixed with milk (porridge). Soft cooked strips of carrot, cooked green beans, soft banana & pear, Apple stew, Spinach & tomato soup. Other cooked vegetables & fruits may now be coarser in texture. Porridge of rice or suji (rava) or nachni or dahlia or mashed banana, mashed boiled sweet potato with carrots with cauliflower. Food should not be salted or sweetened Solid, chewable foods should be introduced. To continue to use cows milk to mix with solids. Hard cheese used as finger foods. Encourage lightly cooked or raw foods. Meat soup can be introduced. Baked fish can be given. Self - feeding should be encouraged. At this age growth velocity is decreased. Physiological anorexia may be seen due to loss of interest in eating & more interest in playing.
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From 6 - 9 months

For this reason feeding should be made interesting by combining it with playing, exploring & interacting with environment. Whole cows milk may be now used as a drink. Energy dense food items like egg, potato, banana, oil, ghee should be used. Child may now take almost all that is cooked for regular meals at home. Weaning is bridge between liquid & solid diet. Hence weaning should be introduced properly to avoid malnutrition. Allow plenty of time for feeding which helps the infant & his bowel to get used. It should be started slowly with small quantities of food increasing gradually. One type of food should be introduced at one time for about 7 days & then another type of food item should be introduced. Introduce new foods mixed with familiar foods Time of the day when you both are relaxed. It should be cheap & easily available. Food items should be culturally accepted. It should be easy to prepare at home. It should provide all necessary nutrients & energy. Over consciousness of parents can lead to overfeeding. Unhygienic preparations can lead to infections. In infants lack of burping can lead to regurgitation, aerophagy or abdominal colic. In toddlers physiological anorexia can lead to refusal of child to accept food. Rumination due to psychological disorder.

Methods of weaning

Type of weaning food

From 9 - 12 months

Problems during weaning

Toddlers (1 - 3 yrs)

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Vaccination ?????????????? ??? ?????????????????? ????????????? ???????????????? ???????? ??????? ???????????????? ????????? ??????? ?????????????????? ?. ?? 26/81

Natural

Artificial Natural (active (passive immunization) immunization)

Artificial

Immunization is the process of making the body resistant to certain prevalent diseases & it is achieved by means of vaccination. Vaccination or immunizations are the terms used interchangeably. Both the terms mean process of giving vaccines to children so that they develop immunity or resistance against that particular disease. Vaccination - It is administration of any vaccine or toxoid for prevention of disease. (active) Immunization - It is a process of inducing immunity artificially or either by vaccination (active) or administration of antibody (passive).
Vaccines Live Killed

F/b exposure to microbe. Antigen recognition by b & t cells, leads to antibody secretion by plasma cells (B) & (T) CD4 cells &B&T memory cells. (Smallpox, TB)

Antigens From mother introduced through by vaccination placenta stimulate cell IgG from mediated & breast milk IgA antibody mediated response

Intravenous immuno globulins i.e. antibodies & antitoxins

Herd immunity (or community immunity)

Bacterial Viral
Types

BCG, Typhoid Polio. MMR, Yellow fever

Cholera Pertusis, Tetanus, Diphtheria, Pneumococcal Polio (Salk), Rabies, Hepatitis b, Japanese encephalitis

Natural acquired

Species Racial Individual Active Passive Natural Artificial Natural Artificial

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The success rate of vaccination program depends on the vaccination status of a community. Higher the number of vaccinations, healthier is the community for that particular disease. This is why incidence of measles, Diphtheria, Pertussis & Poliomyelitis has been minimized to a great extent. It usually takes 14 days to one month for the child to develop immunity after the vaccination. Any child acquiring infection during this period will not be protected. Most of the vaccines give 80 - 100% protection. But, in a community if all children are vaccinated the risk of transmission is reduced & thus incidence of disease becomes very low (e.g. pulse polio vaccination). It describes a type of immunity that occurs when the vaccination of a portion of the population (or herd) provides protection to unprotected individuals. Herd immunity theory proposes that, in diseases passed from individual to individual, it is more difficult to maintain a chain of infection when large numbers of a population are immune. The higher the proportion of individuals who are immune, the

lower the likelihood that a susceptible person will come into contact with an infectious individual. Vaccination acts as a sort of or firewall in the spread of the disease, slowing or preventing further transmission of the disease to others. Unvaccinated individuals are indirectly protected by vaccinated individuals, as the latter will not contract & transmit the disease between infected & susceptible individuals. Hence, a public health policy of herd immunity may be used to reduce spread of an illness & provide a level of protection to a vulnerable, unvaccinated subgroup. Since only a small fraction of the population (or herd) can be left unvaccinated for this method to be effective, it is considered best left for those who cannot safely receive vaccines because of a medical condition such as an immune disorder or for organ transplant recipients. The proportion of immune individuals in a population above which a disease may no longer persist is the herd immunity threshold. Its value varies with the virulence of the disease, the efficacy of the vaccine & the contact parameter for the population. No vaccine offers complete protection, but the spread of disease from person to person is much higher in those who remain unvaccinated. It is the general aim of those involved in public health to establish herd immunity in most populations. Complications arise when widespread vaccination is not possible or when vaccines are rejected by a part of the population. As of 2009, herd immunity is compromised in some areas for some vaccine - preventable diseases, including pertussis & measles & mumps, in part because of parental refusal of vaccination. Herd immunity only applies to diseases that are contagious. It does not apply to diseases such as tetanus (which is infectious, but is not contagious), where the vaccine protects only the vaccinated person from disease.
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Herd immunity should not be confused with contact immunity, a related concept wherein a vaccinated individual can pass on the vaccine to another individual through contact.

Immunization Active

It includes stimulation of the immune system to produce antibodies (B cells) & cellular (T cells) immune response that protect against the infectious agents. - usually prior to infection These Antibodies developed by false infection then fights when real infection occurs, hence avoiding illness. Vaccines are antigens that provoke a response in the body to produce antibodies that fight infection & reserve it in the body. Whenever a disease causing body strikes a vaccinated child, the immune system (from that reserved stimuli) has the ability to protect body & hence does not allow infection to grow & cause disease. This type of immunity is called Active Immunity. It provides temporary protection through administration of exogenously produced antibody such as immunoglobulin & antibody It also occurs transplacentally usually prior to infection. Passive immunization is where pre - made antibodies are given to a person. Passive immunization is naturally acquired when antibodies are being transferred from mother to fetus during pregnancy, to help protect the fetus before & shortly after birth. Sometimes, when young children are exposed to dangerous diseases for which they are not vaccinated, then they are given immunoglobulin. This is artificial passive immunization & is normally given by injection as a emergency treatment option. Immunoglobulin are readymade antibodies given to protect the baby for sometime till they are vaccinated & their active immunity starts to work.

Passive

Whenever disease causing bacteria/virus strikes us for the first time, we fall sick because our body is not prepared to deal with such infection. But slowly body learns to fight this infection by producing specific antibodies. These antibodies are the main defense - line of our body combating external forces. Therefore second time when such infection occurs, the body behaves smartly & uses antibodies (outcome of pervious infection) to fight it. Hence we dont fall ill the second time.

Active immunization

Active immunization entails the introduction of a foreign molecule into the body, which causes the body itself to generate immunity against the target. This immunity comes from the T cells & the B cells with their antibodies. Active immunization can occur naturally when a person comes in contact with, for example, a microbe. If the person has not yet come into contact with the microbe & has no pre - made antibodies for defense (like in passive immunization), the person becomes immunized. The immune system will eventually create antibodies & other defenses against the microbe. The next time, the immune response against this microbe can be very efficient; this is the case in many of the childhood infections that a person only contracts once, but then is immune. Artificial active immunization is where the microbe, or parts of it, is injected into the person before they are able to take it in naturally. If whole microbes are used, they are pre - treated, attenuated vaccine.
Passive immunization

Passive immunization occurs physiologically, when antibodies are transferred from mother to fetus during pregnancy, to protect the fetus before & shortly after birth. Artificial passive immunization is normally administered by injection & is used if there has been a recent outbreak of a particular disease or as an emergency treatment for toxicity (for example, for tetanus). The antibodies can be produced in animals (serum therapy) although there is a high chance of anaphylactic shock because of immunity against animal serum itself. Thus, humanized antibodies produced in vitro by cell culture are used instead if available.
Autoimmune diseases

Passive immunization is where pre - synthesized elements of the immune system are transferred to a person so that the body does not need to produce these elements itself. Currently, antibodies can be used for passive immunization. This method of immunization begins to work very quickly, but it is short lasting, because the antibodies are naturally broken down & if there are no B cells to produce more antibodies, they will disappear.
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To function properly, t cells must have two characters Self recognition - They must be able to recognize own MHC (Major histocompatibility) antigens. 2) Self tolerance - They must lack reactivity to peptide fragments from your own proteins. Loss of self tolerance leads to autoimmune diseases. Vaccines are agents derived from bacteria or viruses either as part or as a whole such that they lose the ability to produce disease but retain the ability to induce antibodies in response. The purpose of vaccines is to boost immunity of the body to fight infection. Normally in many diseases the disease - forming germ enters the body, produces the disease & subsequently the body mounts immune response or fighting power against the germ & lastly one recovers from the disease. Here immunity against disease is produced after one has suffered from the disease. A vaccine is nothing else but whole or part of the disease germ, which has been processed or modified in such a way than it has lost its capacity to produce disease but it can still induce immunity or fighting power by body when administered in the body. Hence by vaccination one develops immunity without suffering from the disease. 1)
Types of vaccines

Vaccines can be oral vaccines like oral polio vaccine or oral typhoid vaccine or it can be injectable vaccine like DPT vaccine

or hepatitis B vaccine. Vaccines can be single vaccine like the measles vaccine or combination of more than one vaccine like the MMR vaccine (which acts against measles, mumps & rubella) or the DPT vaccine (which acts against diphtheria, pertussis & tetanus). Injectable vaccines can be given subcutaneously i.e. below the skin like the measles vaccine or given intramuscularly i.e. in the muscle like DPT vaccine. Lastly vaccines are usually given prophylactically i.e. before the exposure to the disease germs like most of the vaccines e.g. polio vaccine, DPT, vaccine etc. Some vaccines work when given even after the exposure to the disease germ like the rabies vaccine, which is given after the dog bite.
Live attenuated Killed or inactivated detoxified agents. Live attenuated

Age Birth - 15 days

Vaccine

6 weeks - 8 weeks

10 weeks - 12 weeks 14 weeks - 16 weeks 6 months - 9 months

Active 1) 2) 1)

15 months - 18 months

5 years 10 years 15 16 years Vaccine

Organisms multiply in the recipient until desired immune response occurs, similar to that with natural infection. Thus live attenuated viral vaccines are likely to confer lifelong protection with single dose. They contain live bacteria/virus that has been altered so it cant cause disease. e.g. BCG, Polio, Mumps, Measles. Exception OPV oral feeding does not always result in infection.
Killed agents

BCG, OPV zero dose, Hepatitis B Vaccine 1st dose. DPT 1st dose, OPV 1st dose, Hepatitis B Vaccine 2nd dose. DPT 2nd dose, OPV 2nd dose. DPT 3rd dose, OPV 3rd dose. OPV 4th dose Hepatitis B Vaccine 3rd dose Measles vaccine. MMR (Measles, Mumps, Rubella) DPT 1st Booster dose, OPV 1st Booster dose. DPT 2nd Booster, OPV 2nd Booster. TT (Tetanus Toxoid)3rd Booster dose, Hepatitis B Vaccine Booster dose. TT 4th Booster dose.
Disease Prevented

Diseases prevented by vaccines

2)

Do not multiply in the recipient. Many killed vaccines which have a lesser antigenic mass require booster vaccinations. They contain bacteria Killed with chemicals. E.g. Typhoid, Cholera, Hepatitis A, Plague & injectable poliomyelitis. The schedule recommended by the Indian Academy of Pediatrics is as follows :
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BCG OPV (Oral Polio Vaccine) DPT (Triple Vaccine)

Hepatitis B Vaccine Measles Vaccine MMR Vaccine

Tuberculosis Poliomyelitis. D : Diphtheria, P : Pertussis (Whooping Cough), T : Tetanus. Hepatitis B Measles M : Mumps, M : Measles, R : Rubella (German Measles).

Precautions

It specifies a condition in which a vaccine may be indicated if the benefit to an individual outweighs the risk & consequence of adverse event. OPV dose can be given during diarrhea but should not be counted & an extra dose in the schedule should be given One can feed the child including breast feeds before & after any vaccination.
Contraindication

hyperpyrexia (fever > 1050C) with DPT, which must be reported immediately to the doctor.
Other considerations

It indicates that the vaccine should not be administered Anaphylactic reaction to previous dose of same vaccine. Live vaccines are generally contraindicated in immunocompromised persons. Immunosuppressive therapy Corticosteroid therapy Encephalopathy following DPT vaccination. Severe egg allergy in measles vaccine prepared in chick fibroblast cells. Minor illness like mild cough, cold, loose stools, vomiting or even mild fever is not a contraindication for vaccination Common fever, temporary swelling, redness, pain, induration at site. Mild pruritis, urticaria & angioedema. Serious broncospasm, laryngeal edema, shock, CVS collapse. Patient can get pain, redness, swelling at the injection site. Rarely a nodule may form which remains for few weeks especially following DPT. Rarely child can develop fussiness, irritability, anorexia, vomiting, diarrhea, excessive crying etc. especially after DTP injection Lastly there could develop severe reaction like convulsion, depressed responsiveness, altered consciousness, shock,
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Cold chain is important to maintain vaccine potency. Minimum interval between two doses should be at least 1 month. Antibodies appear after 1 - 2 wks of immunization. 2 - 3 i.e. BCG +OPV+DPT vaccines can be given at same time. Different vaccines should not be mixed together. If child misses one dose, whole schedule is not to be repeated.

Minimum gap between 2 vaccines

any number of vaccines can be given on same day at separate sites but if not given on same day there should be gap of 4 weeks between two vaccines in general. One should not give one vaccine today, second 7 day & 3rd vaccine after another 7 days. Extra doses of OPV like in pulse immunization or ring immunization is notable exemption to this rule. Some vaccines like rabies vaccine have schedule where 5 doses are given in 1 months time. Again rabies vaccine or tetanus toxoid when indicated should be started as soon as possible irrespective of vaccines received in recent past
Precautions to be taken after vaccination

Side effects

Keep firm pressure for few minutes at the injection site with a spirit swab. Do not massage or rub at the injection site. Wait in the consulting room for another 30 minutes should any reaction develop following vaccination. Note down carefully when to come back for next vaccination. Inform the doctor immediately if the child develops any reaction or abnormal behavior or habits following vaccination in the next few days.
Immunizing agents Active

1)

Vaccines - A suspension of proteins, polysaccharides or nucleic agents of live attenuated or killed pathogens that induce specific responses that inactivate, destroy or suppress the pathogen.

2)

Toxoid - A purified or modified bacterial toxin that has been made non toxic but retains capacity to stimulate the formation of antitoxin. They contain Toxins/poisons produced by germs which are made harmless. e.g. Diphtheria & Tetanus.

Vaccine carriers

Passive

3)

Immunoglobulin - pre - formed antibodies derived from human blood & primarily used for maintenance of immunity in immunodeficient persons or for passive immunization available in I. M. & I. V. preparations. 4) Anti - toxin - pre - formed antibodies derived from serum of animals after stimulation with specific antigens. Used for passive immunization. Adjutants - agents used to increase immune response e.g. aluminum salts in toxoids.
Cold chain

1) 2) 3) 4) 5)

The equipment & the system of keeping the vaccines cold at right temperature from the manufacturer at the centre to the beneficiary in the periphery is called as cold chain. All vaccines must be stored at +20 to 8o c. If not stored properly vaccine loses its potency. Heat, sunlight & prolonged power failure can damage vaccines. t series vaccines damaged by freezing. These are lined with pipes of ice. Act as buffer in case of power failure. No freezer compartment in ILR. In ordinary refrigerators Freezer - storage of ice packs. Top compartment OPV, measles, MMR. Middle compartment - BCG, T - series & diluents. Lower compartment - IPV, bottles of water Door compartment no vaccines stored.
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Used to bring vaccines for a days use at peripheral centre. Contains frozen ice packs. Can carry 8 10 vials of vaccine for a 6 - 8 hrs session. Reverse cold chain it is the system for sending vaccines cold at right temperature from the periphery to the laboratory for potency checking. Unimmunized child of age 1 - 5 yrs Primary immunization - should receive 3 doses of OPV & DPT with BCG at first visit. Measles at 3 rd visit. Age > 5yrs DT replaces DPT only 2 doses of OPV & DT BCG if montoux is negative. Minimum doses to be given in age < 5yrs 2 doses of TT to pregnant women 1 dose of BCG 5 doses of OPV 4 doses of DPT 1 dose of DT 1 dose of MEASLES.
BCG - Bacilli Calmette Guerine (live)

ILR (ice lined refrigerator)

BCG vaccine is a live bacterial vaccine given for protection against tuberculosis, mainly severe forms of childhood tuberculosis. BCG should be given as early as possible in life, before child comes in contact with tuberculosis. It can be given up to 5 years of age. If it is given beyond 6 months it is preferable to do a prior Mantoux test to see if the patient is already sensitized to tuberculosis. If patient is already sensitized as shown by positive MT, BCG is not necessary India - India introduced BCG mass immunization in 1948, the

first non - European country to do so.

WHO BCG policy WHO recommends that BCG be given to all children born in

countries highly endemic for TB because it protects against miliary TB & TB meningitis. Initially given orally 1921 - 1925. intradermally given since 1927. - given to induce benign, artificial primary infection of tuberculosis. Types - 1) Liquid fresh vaccine 2) Freeze dried vaccine Composition freeze dried vaccine is packed in dark colored ampoules & wrapped in black paper. each ampoule is 20 dose & should be prepared by diluting with 2 ml normal saline. Dosage 0.1 ml (o.1mg) =0.1 to 0.4 million bacilli. below 4 wks of age 0.05ml Route intradermal. At the insertion of deltoid muscle in left arm. Given only in left arm for universal identification By convention BCG scars are looked for over the left arm & hence it is easier to recognize for the doctor when parents do not remember whether BCG was given in the past or not. Hence BCG should only be given over left arm & nowhere else. A wheal or swelling of 6 mm is raised above the surface. No spirit or antiseptic should be applied over the site before injection.
Local care at injection site

BCG can be given with other vaccines except Measles & MMR. In fact, BCG is given along with zero doses of OPV & 1st Dose of Hepatitis B vaccine at birth. BCG should not be given along with measles or MMR Reaction - ID BCG given Development of papule at site (indication of multiplication of bacteria) (5 wks) Size increases to 5 8 mm (6 wks) Ulcer formation (8 - 12 wks) Heals with permanent, rounded scar of 4 - 8 mm diameter.
Normal reaction to BCG vaccine

Injection site should not be pressed or rubbed. It should not be fomented. Nothing needs to be applied locally. Infact, bath with soap & water should suffice even when it has ulcerated. BCG does not lead to fever. Hence search for another cause & treat accordingly. Formation of scar is neither necessary nor is the only indication of success of BCG vaccine. However it is the only simple & convenient way of determining success of BCG vaccine. It may take 3 - 6 months for the scar to form. If no scar is visible at all after 6 months one needs to do Mantoux test. If negative, one should give repeat BCG
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Immediately after the BCG vaccine there is a small swelling at the injection site, which persists for 6 - 8 hours. After that the swelling disappears & the injection site looks normal. After 6 - 8 weeks a swelling reappears, which looks, like a mosquito bite. It grows in size & forms a nodule, which breaks open & discharges some fluid & forms an ulcer. The ulcer should be kept dry & cleaned with soap & water. No ointment/cream is required. There may be an associated swelling in the armpit or in some cases on the neck. It is nothing to be worried about, but if the swelling increases more than 1 cm in diameter or becomes red or soft or attached to the overlying skin, consult your doctor. The ulcer heals by forming a scar. The whole process takes 2 - 5 weeks. Sometimes this process of ulceration & healing recurs 2 - 3 times. Ultimately the typical puckered scar is formed which remains for lifetime. If ulceration occurs within 7 days of injection, it may be a sign of tuberculosis in the child. BCG significantly decreases the risk of tuberculous meningitis (Brain TB) & other widespread forms of tuberculosis. If no reaction occurs it may be due to faulty administration, loss of potency, measles, immunodeficient states, disseminated T. B.

Accelerated BCG response occurs within 4 days. It occurs if child is previously exposed to mycobacterium tuberculi infection or disease. Except in neonates, a tuberculin skin test should always be done before administering BCG. A reactive tuberculin skin test is a contraindication to BCG. If someone with a positive tuberculin reaction is given BCG, there is a high risk of severe local inflammation & scarring. It is a common misconception that tuberculin reactors are not offered BCG because they are already immune & therefore do not need BCG. People found to have reactive tuberculin skin tests should be screened for active tuberculosis. If BCG is accidentally given subcutaneously, then a local abscess may form (a BCG - oma) that may ulcerate & often requires treatment with antibiotics. If given subcutaneously, BCG causes a local skin infection that may spread to the regional lymph nodes causing a suppurative lymphadenitis. However, it is important to note that an abscess is not always associated with incorrect administration & it is one of the more common complications that can occur with the vaccination. BCG immunization leaves a characteristic raised scar that is often used as proof of prior immunization. The scar of BCG immunization must be distinguished from that of small pox vaccination which it may resemble. BCG is one of the most widely used vaccines in the world, with an unparalleled safety record. BCG immunization causes pain & scarring at the site of injection. The main adverse effects are keloid - large, raised scars. The insertion of deltoid is most frequently used because the local complication rate is smallest when that site is used. If BCG is accidentally given to an immunocompromised patient (e.g. an infant with SCID), it can cause disseminated or life - threatening infection. The documented incidence of this happening is less than 1 per million immunizations given.
Efficacy of BCG vaccine
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In a country like ours where tuberculosis is endemic, children are infected early in life & develop primary TB. In children younger than 3 - 5 years of age, this can spread & lead to severe & serious forms of childhood tuberculosis. BCG being live vaccine itself induces a benign primary infection, which leads to some immunity. Such a child when comes in contact with a patient with tuberculosis can still catch the wild germ & develop primary TB, but the spread will be mostly prevented by previous BCG immunity. Hence such children will not develop serious forms of childhood tuberculosis. Such children when they grow as adults can catch tuberculosis again & develop adult form of tuberculosis which is a different type of tuberculosis altogether. Thus BCG does not prevent adult type of
tuberculosis. DPT (diphtheria, pertusis, tetanus) (killed

DPT is a combination vaccine to protect against Diphtheria, Tetanus & Pertussis (whooping cough). DT protects against diphtheria & Tetanus & TT protects against tetanus.
Types Composition Dosage 0.5 ML Route Site intramuscular (deep) anterolateral aspect of thigh

After receiving the DPT injection, swelling & pain at the injection site & fever up to 72 hours is common. Paracetamol is given for 48 72 hours after DPT to reduce the severity of the effects. Applying ice wrapped in handkerchief over the injection site helps to reduce swelling & pain to some extent Age 68 wks after birth.3 primary doses of DPT vaccine are given at 4 weeks interval starting at 6 - 8 weeks of age along with the 3 primary doses of oral polio vaccine. It is recommended routinely for each & every child. Schedule 3 doses for primary immunization at48 wks interval between each dose.

Booster 15 - 18 mt. & 5 yrs. First booster dose of DPT is given at the age of 15 - 18 months along with the 1st booster dose of OPV. Govt. of India under EPI recommends only DT as the second booster at the age of 4 - 6 years whereas Indian Academy of Pediatrics recommends DPT & OPV as the 2nd booster at 4 - 6 years of age.
Side effects Local side effects : It includes pain, swelling, redness & difficulty

The recommendations differ from authority to authority regarding 2nd booster dose

Indian Academy of Pediatrics feels that the immunity against pertussis & poliomyelitis will wear off by 5 years as will happen for diphtheria & tetanus. This will lead to increased risk of whooping cough & poliomyelitis in adolescents & adults. Hence IAP recommends OPV & DPT & not only DT as the 2nd booster at 4 - 6 years.
The efficacy of DPT vaccine

in walking. It is seen in 30 - 40% of vaccinees. It persists for 24 - 72 hours & responds to paracetamol. Sometimes a nodule forms at the injection site, which may persist for several days to weeks. It may soften & form a sterile abscess. It does not merit any treatment except analgesics. If it shows fluctuation, it can be drained. Systemic side effects : It includes fever, lassitude, anorexia, vomiting, irritability, excessive crying etc. seen in 30 40 % of patients. Fever is usually mild to moderate, lasts for 2 - 3 days & responds to paracetamol Sometimes, Pertussis component of DPT is responsible for fever more than 1050 F, excessive crying & screaming spells lasting for more than 4 hours & convulsions. If a patient develops any of those adverse reactions it is a contraindication to further use of DPT & instead only DT should be used. Such reactions should be immediately reported to doctor.
Treatment of side effects following DPT

Efficacy of diphtheria toxoid & tetanus toxoid is excellent. The protection is seen in nearly 100% of vaccinees with good long - term protection after primary & booster doses of DPT. The pertussis component is a weak candidate & the protective efficacy is seen in 70 - 90% of cases.
Acellular pertussis DPT vaccine

As seen before, the severe adverse side effects seen with DPT are due to pertussis component. It was realized that the reactions were due to components of cell wall of pertussis organism, which are not required for efficacy of vaccine. An acellular pertussis vaccine that does not have whole cell wall of pertussis has been developed that can be routinely used for immunization.
Whole - cell pertussis

Paracetamol or ibuprofen can be used to treat pain, swelling, redness, difficulty in walking & fever. It takes 2 - 3 days for the symptoms to disappear. In case abscess has formed, treat with antibiotics & drainage. Persistent nodule should be left alone, as it does not lead to any other symptoms. Complications encephalopathy, convulsions Contraindications progressive neurological symptoms uncontrolled seizures successive doses of DPT not given if convulsions, encephalopathy, anaphylactic reaction, hyperpyrexia, persistent & high pitched cry for more than 3 hrs.
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Vaccines consist of whole bacteria that have been inactivated & are nonviable. These vaccines contain lipo - oligosaccharide & other cell - wall components that result in a high incidence of adverse effects.
Acellular pertussis

Vaccines contain one or more Bordetella pertussis proteins that serve as immunogens. All acellular pertussis vaccines contain at least detoxified pertussis toxin & most contain other antigens as well, including filamentous hemagglutinin, fimbrial proteins & pertactin. The acellular vaccines are associated with a much lower incidence of side effects.
DT vaccine

It is used in patients where pertussis component is contraindicated & as 2nd booster. DT vaccine has 1/10th dose of diphtheria toxoid than present in DT/DPT. If full dose of diphtheria toxoid is given as present in DT/ DPT in children above 10 years of age, it can lead to serious side effects like heart toxicity, serum sickness like reactions etc. With lack of natural boosting due to mass vaccination, diphtheria can occur beyond 10 - 15 years of age in vaccinees. One needs to give booster of diphtheria at 10 years & maybe every 10 years thereafter to maintain protective titres. DT is useful in such cases as a booster at 10 years (instead of TT).
TT vaccination

desirable or safe to give TT for each & every injury every now & then in such a protected person.
TT administration in an injured child

TT is routinely used for children > 10 years of age as they do not need both Diphtheria & pertussis components. It is given as a booster dose at 10 years & 16 years to children who have received their primary doses/boosters of DPT/DT before. It can be then taken every 5 - 10 years to maintain protection lifelong
TT to pregnant women

A child who has received 3 primary doses of DPT/DT is protected till 15 months of age & does not need TT. If he is 15 - 18 months of age he should receive his first 1st booster of OPV + DPT which will also boost up anti - tetanus immunity. Such a child is protected till 4 years & does not need a TT till that age. If he is between 4 - 6 years he should receive his 2nd booster of DT or OPV + DPT which will boost up his anti - tetanus immunity too. Such a child is now protected till 10 years of age. After this a booster of TT is given at 10years, 16 years & every 5 years thereafter. In between such doses there is no need to give TT for injury.
Effect of frequent TT administration

If TT is given frequently, it will hyper - immunize the patient. Such a patient can develop arthus like phenomenon with development of fever, rash, joint pain, joint swelling etc. Hence it is not desirable to give frequent injections of TT in an otherwise immunized patient.
Immunization in a child already suffered from diphtheria, tetanus & pertusis

A lady who is previously un - immunized should receive 3 doses of TT during pregnancy at 1 - month interval starting the first dose at 28 weeks. The last dose should be at least 30 days prior to the expected date of delivery so that there is enough time for good antibody titres to develop in mother & for it to be passed on to the fetus to prevent tetanus in newborn. During repeat pregnancy, 2 doses of TT are given at 4 weeks interval. Again the last dose is given at least 30 days before delivery.
TT to an adult with injury

An adult who has never received or has received incomplete course of TT before in life should be given 3 doses of TT at 4 weeks interval followed by a booster after 1 year & then every 5 years. If he then develops any injury or requires any surgery there is no need to take anymore TT as he is protected in between the doses. If such an adult has taken the last TT beyond 4 - 5 years in past, he can be given one dose of TT, which acts as a booster. It is neither required nor
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Neither of diphtheria, tetanus or pertussis disease leads to strong immunity. Hence, a person who has recovered from such diseases should receive 3 primary doses & boosters of DPT/DT/TT as appropriate for his age. Measles vaccine is usually without any side effects. However, fever, measles like rash, cough & cold are commonly seen post vaccination. These symptoms do not need any treatment except paracetamol to control the fever. Measles Measles vaccine is given for protection against measles, the typical fever with rash of childhood so well known to most of the people. Route It is given subcutaneous (in the fat just below the skin) over the thigh or the arm.

Age It is given at the age of completed 9 months (270+ days of life). During epidemics of measles the vaccine can be given as early as 6 months, but this should be followed by one more measles vaccine at 9 months. Hence we advise measles vaccine at 9 months followed by MMR at 15 months. Booster dose of measles vaccine

MMR (measles, mumps, rubella) (live)

MMR vaccine is given for protection against 3 common childhood viral diseases namely measles, mumps & rubella (German measles).
Composition Dosage - 0.5 ML Route - sub cutaneous Site - upper arm or anterolateral aspect of thigh. Age - 15 - 18 mt. it is recommended to give measles vaccine at

A booster in form of MMR vaccine is given at 15 - 18 months of age.

Immunization in a child suffered from measles

A child who suffers from measles develops life long immunity. Hence such a child does not need measles vaccine. When in doubt it is better to give measles vaccine as no harm is done even if patient has suffered from measles in past.
The efficacy of measles vaccine

Measles vaccine is an excellent vaccine with more than 90% efficacy with a booster given in form of MMR. Even if a patient who is vaccinated develops measles, it is usually modified & mild with quick recovery & without serious complications.
Side effects of measles vaccine

Measles vaccine is a very safe vaccine. If at all, it leads to mild pain, swelling, induration or fever. It is seen in less than 10% of patients, is transient & mild, lasts for < 24 hours & responds well to paracetamol. It can occur from the day of injection till 5 - 7 days. Sometimes a patient can develop measles like infection with cough, cold, red eyes & rash over skin. Again it lasts for 2 - 5 day & is self limiting.
Measles vaccine contraindications

9 months, which will protect early against measles followed by MMR vaccine at 15 months of age, which will act best against mumps & rubella & will act as a booster for measles. Schedule single dose. Side effects mild fever & rash. Measles though a mild disease in children can occasionally lead to pneumonia & brain damage (SSPE). Mumps is a common cause of morbidity in children with occasional chances of complications like encephalitis & pancreatitis. Rubella or German measles though a benign disease can lead to congenital rubella syndrome if it occurs during pregnancy. Such a child will have cataract, deafness, heart disease, small head, mental retardation & many other complications. Hence MMR vaccine is essential.
Booster dose of MMR vaccine

In patients, with mild egg allergy, measles vaccine can lead to allergic reactions. In cases of severe egg allergy, measles & MMR vaccines are contraindicated. In case with mild egg allergy, measles or MMR vaccines can be given but with strict medical supervision & all the measures of resuscitation & drugs kept ready should the patient develop reaction.
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As of today there is no need to give booster dose of MMR vaccine in India. This is because the routine coverage by measles & MMR vaccine is poor. Therefore naturally occurring subclinical measles, mumps & rubella are common which act like natural booster in vaccinees. A time may come in coming years when the routine coverage of MMR will go up which will lead to drastic reduction in natural infections & hence decrease natural boosting against measles, mumps & rubella. This has been the experience in western countries. At such time a booster of MMR at 5 years (school entry) or 15 years (school exit) is recommended, as is practiced by USA.

Side effects of MMR vaccine

MMR vaccine is a very safe vaccine. If at all, it leads to mild pain, swelling, induration or fever. It is seen in less than 10% of patients are transient & mild, lasts for < 24 hours & responds well to paracetamol. It can occur from the day of injection till 5 - 7 days. Sometimes a patient can develop measles like infection with cough, cold, red eyes & rash over skin. Again it lasts for 2 - 5 days & is self - limiting.
Contraindications of MMR vaccine

OPV far outweigh the rare risk of paralysis. In west, though, it can become a medico legal problem. Hence in west, people use first IPV to induce systemic antibodies & then use OPV, which will lead to local gut immunity without the risk of vaccine induced paralysis due to the partial immunity conferred by prior IPV. IPV can lead to local side effects like pain, swelling, redness & tiredness in 10 20 % of vaccinees. It can lead to fever, which is mild & lasts for 24 48 hours.
Contraindications of polio vaccine

In patients, with mild egg allergy MMR vaccine can cause allergic reactions. In cases of severe egg allergy, measles & MMR vaccines are contraindicated. In case with mild egg allergy, measles or MMR vaccines can be given but with strict medical supervision & all the measures of resuscitation & drugs kept ready should the patient develop reaction.
OPV

OPV is contraindicated in patients with low immunity especially if IPV is available. OPV can be given to a patient with diarrhea, but that dose should not be counted & should be followed by an extra dose. IPV is contraindicated if patient has developed severe adverse effect to its use in past.
Child comes late for polio vaccine

OPV given at the time of birth is called zero polio. Total 5 polio doses are given in the first year of life. Over & above that pulses
polio doses are administered at least twice a year (usually in winter) to all children below 5 years of age, irrespective of number & time of previous polio doses. Availability

Paralytic poliomyelitis can occur till 15 years of age. Most of the children are immune by 5 years naturally due to subclinical infections. Hence, OPV is given to any child who presents till 5 years of age. Such a child should receive 3 primary doses followed by 1st booster 1 year after 3rd primary dose & a second booster 3 years 4 years after the 1st booster dose provided the child is still less than 5 years old then.
Pulse polio immunization

OPV is available as vial containing multi doses. The dose is 2 drops per dose. IPV is available as a single dose vial containing 0.5 ml of vaccine. It is also available as combination vaccines containing IPV+DPT or IPV+DPT +Hepatitis B or IPV + DPT + Hib or IPV + DPT + Hepatitis B + Hib.
Side effects of polio vaccines

OPV has minimum side effects. It can lead to GI upset like diarrhea, vomiting. It does not lead to fever. Most of the side effects seen with OPV +DPT are due to the DPT vaccine. The most important but extremely rare side effect with OPV is vaccine - associated paralysis (VAP). It occurs in 1 in million doses. Massive benefits of
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It is a strategy of mass immunization by which one can eradicate poliomyelitis. Extra doses (pulses) of OPV are given to all children below 5 years of age in an area (like country, state, city) at a time on a given day. Such pulses are repeated every year. The aim is to achieve 100% coverage. Wild poliovirus can survive either in the intestines of a susceptible host (usually children < 5 years of age) or in the sewage water. In the sewage water it can survive only for 48 72 hrs & hence it has to find shelter into another susceptible host for it to survive & to continue cycle of transmission. When you give pulse OPV to all

the children of < 5 years of age, the intestines of these children are flooded by vaccine virus & hence wild poliovirus cannot get entry into it. As wild poliovirus cannot survive for more than 48 - 72 hrs in environment, its circulation will drastically fall. When such pulse is repeated after 6 weeks it still further reduces transmission. Such pulses done every year will ultimately eradicate the wild poliovirus from nature. Additional doses of polio may be given in a particular area if a case of polio is found in that area.
Type Characteristic Composition Age Schedule IPV (SALK) OPV (SABIN)

Inactivated/killed 8 wks initiation 3 doses at 6 wks interval 1st booster 18 mts 2nd - 4 - 5 wks 0.5 ml IM/SC Produce humoral IgM, IgG. IgA in serum. No local immunity prevents paralysis, not reinfection Almost no contraindication

Live attenuated 6, 10, 14 wks Zero dose at birth 6, 10, 14 wks 1st booster 18 mts 2nd 5 yrs 2 drops Oral Both humoral& local immunity. prevents paralysis & intestinal infection useful in epidemics Acute infection, diarrhea, dysentery, leukemia, malignancy, steroid therapy, pregnancy Vaccine induced polio (1/5 million cases) Easy administration, no trained persons required, induces both types of immunity, useful in epidemics, cheap,
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No local immunity, costlier, trained persons required, antibody production slower, difficult to manufacture, more than 1 dose required to induce immunity Contraindications - immunocompromised child.
Disadvantages Polio vaccines General considerations

antibody production even with single dose. Cannot be used in immunocompromised, > 50 yrs, pregnancy, steroid therapy, vaccine induced polio & vaccine failure may occur.

Dose Route Immunity

Repeat OPV administration if child spits Avoid hot liquids, food & breast feeding hour before &after vaccination. Intramuscular injections & tonsillectomy should be avoided during epidemic of polio.

VVM vaccine vial monitor

Contraindications

It is a small square made up of heat sensitive material. It is placed on outer colored circle printed on label of OPV vial. Due to temperature & prolonged storage the color of square changes from pink &becomes darker. It is compared with the color of outer circle to check potency.
Hepatitis B

Complications Advantages

Safe in immunocompromised steroid therapy, 1st vacation, pregnancy

Hepatitis B (HBV) is a type of virus that leads to jaundice & infective hepatitis. HBV leads to acute hepatitis & most of the patients recover.5 10% develop chronic carrier state. Again of these carriers, 30% will develop chronic liver disease & some will develop liver cancer.1 2% of patients with HBV infection develop fulminant hepatitis which carries > 80% mortality.
Modes of transmission of HBV

Vertical transmission occurs from Hepatitis B positive pregnant

women to their babies during the perinatal period. Transmission may also occur due to close contact e.g. amongst family members or at day care centers. It can also spread via blood products, contaminated needles, surgical instruments, IV drug abuse, tattooing, acupuncture needles, ear piercing etc. Last is the sexual route of transmission, which occurs when one partner is infected.
Hepatitis B vaccine

Typhoid

Hepatitis B vaccine protects against infection by HBV. Ideally it should be given to every individual. What is the schedule of Hepatitis B immunization? Schedule consists of giving 3 doses at birth, 6 weeks along with OPV/DPT & 3rd dose can be given at 14 weeks. A booster is not required for 5 - 10 years.
If the child comes late for subsequent doses

Considering the high incidence of typhoid in our country, it would be worthwhile to administer this vaccine. Newer vaccines now available are administered as a single dose injection after two years of age. Boosters are necessary every 3 years. In a child more than 6 years old, an oral (capsule) preparation is available. This is given as a single capsule every alternate day for 3 doses. The oral vaccine also needs to be taken every 3 years for continued protection.
Types of typhoid vaccine Vi antigen vaccine : It is an inactivated vaccine available as Oral ty21a vaccine Availability

injectable form. : This is an oral live vaccine.

There is no need to restart the course. Instead just complete the remaining doses as per original schedule. However such delays are not desirable as the child remains unprotected till the course of 3 doses is completed.
Side effects of Hepatitis B vaccine

The Vi antigen vaccine is available as single dose ready to use vials containing 0.5 ml of vaccine or as multi dose bulbs containing 4 10 doses (2 5 ml) depending on brand used. Some brands are available as 0.5 ml containing mono dose prefilled syringes. The ty21a oral vaccine is available as a pack of 3 capsules.
Schedule

The side effects of the vaccines are very few if any. Local reactions including redness, pain & swelling at injection site.
Immuno compromised children

Children with leukemia, on chemotherapy, multi transfused thalassemics, patients on high dose long - term steroids & patients on hemodialysis have poor seroconversion following conventional schedule. Hence it is recommended to double the dose of vaccine. Even children with Downs syndrome show poor seroconversion & titres & should be given double the normal doses should Hepatitis B vaccine be given to a carrier or to a patient who has recovered from HBV infection? Neither the carrier nor the patient who has recovered needs Hepatitis B vaccine. In fact, a patient of HBV infection develops protective antibodies to surface antigen (anti HBs) on recovery. There is no risk associated with vaccination, but it is a total waste of such an expensive vaccine.
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Vi antigen vaccine is given in the dose of 0.5 ml intramuscularly either on thigh or arm. It is given as a single dose. Oral ty21a vaccine is a course of 3 capsules given orally on alternate days. The capsules should be swallowed intact & not opened or chewed. In most, the pack contains 4 capsules & such 4 capsules are given on alternate days. Liquid form of oral ty21a vaccine in sachet form is more effective than the capsule form. But sachet form is not available in India. Typhoid fever can occur at any age.10% of cases occur in infants < 1 year of age. The most common group to be affected is school going children & adolescents. Hence earlier the vaccine is given better it is. The Vi antigen vaccine can be given only after completing 2 years of age. Oral ty21a vaccine is in form of capsules & the capsules need to be swallowed intact. Though the vaccine is effective after 2

years of age, practically a child above 46 years of age can swallow capsules. Hence it is recommended after the age of 46 years.
Side effects of typhoid vaccines Vi antigen vaccine : It can lead to local side effect like pain, swelling,

redness, tenderness etc. The side effects are very mild & are seen in < 10% of vaccinees, last for 24 hours & respond to paracetamol. Systemic side effects are rarely seen & include mild fever lasting for 24 hours, which responds well to paracetamol. Oral ty21a vaccine : It leads to mild GI discomfort like pain in abdomen, vomiting, diarrhea & occasionally mild fever. Again, the reactions are less common, mild & self - limiting. Typhoid is an endemic disease in India with estimated incidence of 5 million cases per annum. The currently available vaccines are safe & efficacious. It must be given to all food handlers, travelers to endemic areas, those who eat outside open food frequently. It should also be given to those who have suffered typhoid fever as typhoid does not lead to protective immunity & relapses are known to occur. In such cases, it is given 4 weeks after complete recovery from typhoid fever.
Contraindications to typhoid vaccine

i) ii)

iii)

Oral ty21a vaccine is contraindicated in immune compromised host, as it is a live vaccine. Antibiotics that act against typhoid should not be given 5 days before, during & after vaccination with oral ty21a vaccine. Lastly, any child who has shown severe reactions to previous typhoid vaccine should not be given the same vaccine again.
Varicella zoster

iv)

Varicella or chickenpox is a highly contagious disease with peak age at 5 - 9 years leading to rash. It is a self - limiting disease & occasionally leads to fever, pneumonia, liver damage & brain infection. Chicken pox can be very severe in immunocompromised patients e.g. in patients with cancer & can even lead to death. If it occurs during pregnancy, there are 25% chances of transmission of the virus to fetus. If it occurs in first half of
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pregnancy it will lead to fetal varicella syndrome characterized by scarred skin, limb defects & eye defects. If it occurs in 2nd half of pregnancy, the child has chances of developing herpes zoster at an early age. If it occurs within 21 days of delivery, there are 25% chances of newborn developing chicken pox. Varicella vaccine is definitely indicated in certain high - risk groups : Immuno - compromised host : Varicella can be very severe in immunocompromised host as seen before. Hence such children should be immunized irrespective of age. One needs to give 2 doses of injections. Care should be taken to stop chemotherapy/ steroids for at least 2 weeks before & after vaccination or at least for the first dose of vaccination. Non - pregnant women of childbearing age. Adults in contact with children who are at high risk of complications of chicken pox e.g. family members of a child with leukemia. Those at high risk of exposure to chickenpox like teachers of young children, college students, day - care nursery workers, military personnel etc. Health personnel. A normal child who develops chickenpox suffers for 1 - 2 weeks of disease. The complications are rare & mortality even more rare. But there are occasional cases of complications like encephalitis, pneumonia & even death in normal children. More important, it leads to social problems like the child missing school or even final exams as it usually occurs in months of Jan - March every year. Even the parents will have to take leave & lose wages for 7 - 14 days.

Schedule

It is to be given subcutaneous over left arm or thigh. It is given at 12 - 15 months of age. In children < 13 years, only one dose is required. In children > 13 years & adults, 2 doses are given at 6 - 8

weeks interval. Immuno - compromised patients need 2 doses irrespective of age.

Side effects

it occurs in immuno - compromised patients like HIV, it can lead to complications like pneumonia & brain damage.
EPI schedules as recommended by Govt. of India

It is a very safe vaccine. Local side effects seen include pain, redness, swelling in < 5% of vaccines. Systemic side effects like fever are rare.3 - 7% of vaccines can develop varicella like rash, which are very mild with rapid recovery. It can occur within 6 weeks of vaccination.
Contraindications

Firstly it is not indicated in those who have definite history of chickenpox in the past. It is contraindicated in - patients with neomycin hypersensitivity as the vaccine contains traces of neomycin. It is contraindicated in patients with immunodeficiency including symptomatic HIV & in children with acute leukemia on chemotherapy. For patients with leukemia in remission, chemotherapy should be withheld for at least 2 weeks before & after the first dose of vaccine. Similarly patients on high dose of long - term steroids should be given the vaccine when steroids are temporarily withheld for at least 2 weeks before & after vaccine. It is contraindicated during pregnancy & in fact pregnancy should be avoided for at least 6 - 8 weeks after vaccination.
Herpes zoster

Birth - 15 days 6 weeks - 8 weeks 10 weeks - 12 weeks 14 weeks - 16 weeks 6 months 9 months (completed) 15 months - 18 months 4 years - 6 years 10 years 16 years

BCG + OPV (ZERO DOSE) + Hep B1 OPV1 + DPT1 + Hep B2 OPV2 + DPT2 OPV3 + DPT3 Hep B3 Measles vaccine 1st booster of OPV/ DPT DT vaccine Tetanus Toxoid Tetanus Toxoid

Vaccination schedule recommended by Indian Academy of Pediatrics (IAP) IAP Time Schedule of routine vaccination Optional vaccines

Varicella & herpes zoster are manifestations of the same virus i.e. varicella virus. When a person comes in contact with the virus for the first time, he develops chickenpox. Even when he recovers, the virus remains latent in the nerves for years. In 15 - 20% of them, the virus is able to spread albeit locally along the nerve root causing herpes zoster. This occurs due to natural fading of immunity & hence occurs after the age of 40 - 50 years. Herpes zoster, though usually a benign disease lasting for 7 10 days can lead to complications. Firstly, it can lead to pain, which can go on for months to years. Secondly, if it involves the face, it could also involve the eyes & unless one takes proper precaution, this can lead to permanent damage to vision. Lastly, herpes zoster if
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These include typhoid vaccine & Hib vaccine. These are costly vaccines. But for the cost, they are recommended as routine vaccines for all children. The currently available typhoid vaccines given are after 2 years of age & repeated every 3 - 5 years thereafter. Common childhood diseases like hepatitis A & chicken pox lead to more suffering but very less chance of death. These diseases are usually mild & self - limiting in children & hence option of routine vaccination of children is left to parents. This makes their use optional as per wishes of parents. Chickenpox & Hepatitis A vaccine can be given after 1 year of age.

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Diaper dermatitis

It is caused by over hydration of the skin, maceration, prolonged contact with urine & feces, retained diaper soaps & topical preparations & is a prototypical example of irritant contact

dermatitis. Signs & symptoms are restricted in most individuals to the area covered by diapers. Diaper rash affects the areas within the confines of the diaper. Increased wetness in the diaper area makes the skin more susceptible to damage by physical, chemical & enzymatic mechanisms. Wet skin increases the penetration of irritant substances. Super hydration urease enzyme found in the stratum corneum liberates ammonia from cutaneous bacteria. Urease has a mild irritant effect on non intact skin. Lipases & proteases in feces mix with urine on non intact skin & cause an alkaline surface pH, adding to the irritation. (Feces in breastfed infants have a lower pH & breastfed infants are less susceptible to diaper dermatitis) The bile salts in the stools enhance the activity of fecal enzymes, adding to the effect. Candida albicans has been identified as another contributing factor to diaper dermatitis Diaper dermatitis commonly affects infants, with peak incidence occurring when the individual is aged 9 - 12 months. Children with a previous medical history of eczema or atopic dermatitis may be more susceptible to diaper dermatitis. Nutritional history may also be an important factor to consider in diaper dermatitis. A biotin - poor diet, such as occurs with elemental formula alone, may result in perioral erythema, developmental delay, loss of hair & hypotony (in addition to diaper dermatitis). Lack of zinc - binding ligands in the intestine, such as in the autosomal recessive disorder acrodermatitis enteropathica, may result in a triad of hair loss, dermatitis & diarrhea.
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Physical

Pathophysiology

Patients with diaper dermatitis present with an erythematous scaly diaper area often with papulovesicular or bullous lesions, fissures & erosions. The eruption may be patchy or confluent, affecting the abdomen from the umbilicus down to the thighs & encompassing the genitalia, perineum & buttocks. Genitocrural folds are spared in irritant dermatitis, but often involved in primary candidal dermatitis. Children with diaper dermatitis have marked discomfort from intense inflammation.
Causes

Age

The following causes have been noted : Over hydration of the skin Maceration Prolonged contact with urine & feces Retained diaper soaps Topical preparations More than 3 diarrheal stools per day Side effects of oral antibiotics Contact Dermatitis Herpes Simplex Virus Infection Histiocytosis Scabies Syphilis Varicella

Differential diagnosis

Acrodermatitis Enteropathica Atopic Dermatitis Biotin Deficiency Candidiasis Child Abuse & Neglect : Physical Abuse& Sexual Abuse
Laboratory Studies

Diagnosis of candidal dermatitis can be established by potassium hydroxide (KOH) preparation or culture, but is usually not necessary in patients with diaper dermatitis.
Treatment

Provide education regarding diaper dermatitis to patient,

o o o

parents, and/or caregivers Ideally, the first - line therapy for individuals with diaper dermatitis is zinc oxide ointment. Zinc oxide is an inexpensive treatment with the following properties : Antiseptic & astringent Significant role in wound healing Low risk for allergic or contact dermatitis The safest OTC emollient available for newborns is pure white petroleum ointment, which acts by trapping water beneath the epidermis. Another safe alternative is Aquaphor ointment, which is composed principally of white petrolatum, mineral oil & wood wax alcohol. It is more expensive than pure white petrolatum ointment.

that is both a skin protectant & has a drying effect on vesicular or wet dermatoses. Pediatric - Apply to diaper area after every diaper change Nystatin - Fungicidal & fungistatic antibiotic obtained from Streptomyces noursei. Pediatric - Apply sparingly over affected area bid Econazole - Effective in cutaneous infections. Pediatric - Apply to the affected skin & surrounding areas q12 - 24h for 2 - 4 wk Hydrocortisone, topical - An adrenocorticosteroid derivative suitable for application to skin or external mucous membranes. It has mineralocorticoid & glucocorticoid effects resulting in anti inflammatory activity. Pediatric - Apply sparingly to diaper area bid

Activity

The diaper area may be left open to air or covered with a topical emollient. Medical therapy for diaper dermatitis includes the use of protective topical agents, topical anticandidal agents, and, possibly, topical low - potency steroids.
Protective topical agents

Ideally, first - line therapy for diaper dermatitis is zinc oxide ointment. The safest over - the - counter (OTC) emollient available for newborns is pure white petroleum ointment. Another safe alternative is Aquaphor ointment, which is principally composed of white petrolatum, mineral oil & lanolin. It is more expensive than pure white petrolatum ointment. Petrolatum - Traps water beneath the epidermis. Pediatric - Apply to diaper area after every diaper change Zinc oxide - Have antiseptic & astringent properties. Plays significant role in wound healing with low risk for allergic or contact dermatitis. Pediatric - Apply to diaper area after every diaper change Petrolatum, zinc oxide, aluminum acetate solution - Combination product
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