 Jaundice = visible manifestation in skin and

sclera of elevated serum bilirubin

 Visible in adults at STB >2mg/dl

 In neonates if STB> 5 mg/dl
 Incidence of neonatal jaundice

Term : Occurs in60%

Preterm : 80% of preterm neonates

Jaundice is the most common condition that requires
medical attention in newborns.
Bilirubin metabolism
 Typesof bilirubin
Unconjugated bilirubin Conjugated bilirubin
(Indirect ) (Direct )

• Bind to albumen • Conjugated with glucoronic

acid

• Fat soluble • Water soluble

• Can cross blood brain barrier • Excreted in urine andstool

• Toxic in high level to brain • Not toxic

 Unconjugated hyperbiliruninemia
• TSB above normal and conjugated fraction < 15%
• Causes
• A) over production of bilirubin
1)Increase rate of hemolysis ( retic count high)
a) With positive coombs test
-Rh incompatibility
-ABO blood group incompatibilty
• b) with negative coombs test
• -sherocytosis
• -thalassemia
• -G6PD deficiency
• 2) non hemolytic causes (retic count normal)
• a. extra vascular hemorrhage
• cephalohematoma,extensive bruising
• internal hemorrhage (IC bleed)
• b. polycythemia : increase RBC load leads to
increase RBC turnover
• c. exaggerated enterohepatic circulation of
bilirubin : GI tract obstruction
•
• B ) Decrease Rate Of Conjugation
• Glucoronyl transferase enzyme may be
• a. absent – criggler najjar syndrom 1
• b.deficient-- criggler najjar syndrom 2
• gilbert syndrom
• c. Immature– physiologic jaundice
• d. under stimulated– hypothyroidism
,hypoxia,hypoglycemia
• e. inhibited – breast milk jaundice ,
• lucy driscoll syndrom
Clinical features :
Color of sclera and skin : bright yellow or orange
Color of urine : usually normal
Color of stool : may be dark
Risk of kernicterus
Risk of anaemia
• Timing of jaundice
In 1st day of life : Rh and ABO incompatibility
In 2nd -3rd day: physiologic jaundice
criggler najjar syndrom
After 1st week: breast milk jaudice
hemolytic anemia
Persistent during 1 month: criggler naggar syndrome
pronlonged physiologic jaundice in infant
with hypothyroidism or git obstruction
brest milk jaundice
-
 Physiologic jaundice

• Commonest cause
• Etiology : a.decrease glucuronyl transferase
activity
• b.short life span of neonatal RBC
• Unconjugated hyperbilirubinemia
• Rate of rise 1-3 mg/dl/day
• No pallor organomegaly ,no risk of kernicterus
 Full term preterm

incidence 40% 60%

onset 2nd –3rd day 3rd –4th day

Peak at 4th day 6th -8th day

disappear By end of 1st week By end of 2nd week

Peak level 12mg /dl 15mg/dl

• Diagnosis : by exclusion
• Treatment :fullterm ,usually no treatment
may be needed in
VLBW:phototherapy
 Pathological jaundice
• Criteria:
• at any time even 1st day (always pathological)
• Associated problem(anemia,organomegaly,sign of
sepsis,kernicterus)
• Persistent(>1 week in full term & 2 week in
preterm)
• Nonrespons to phototherapy
• Peak level >13mg/dl in FT & >15 mg/dl PT
• Rate of rise >5mg/dl/day or 0.5 mg/dl/hour
• Direct hyperbilirubinemia is always pathological
 Breast milk jaundice
• Incidence:- Affects 2-4 % of breast fed, healthy
full term.
• Clinical picture:Instead of the usual fall of serum
bilirubin by the end of first week it continues to
rise
• With a maximal level of 10-30 mg/dl.
• Peaking at 1 0-15 days of age
• Slowly decline by 3-12 weeks of age.
• If nursing is interrupted, bilirubin level fall quickly
• Etiology: Breast milk may contain
pregnandiole which inhibit glucoronyle
transferase enzyme
 Gilbert Disease

• Etiology -Autosomal dominant disorder.

• Decreased hepatic glucoronyle transferase
level.( was thought to be due to deficiency of
Z& Y proteins )
• Clinical picture - Mild hyperbilirubinemia
usually need no treatment
 Criggler-Naijar Syndrome Type I
Etiology -Autosomal recessive disorder.
Absent glucoronyle-transferase enzyme
• Clinical picture - Severe disease; very high
level of indirect bilirubin, in absence of
hemolysis , unresponsive to phenobarbitone
• Diagnosis - No glucoronyl conjugated bilirubin
in duodenal aspirate
• Enzyme assay in liver biopsy
 Criggler-Naijar Syndrome Type II
Etiology - Autosomal dominant disorder.
Partial deficiency of glucoronyl-transferase
enzyme
Clinical picture - Responsive to phenobarbitone
(i.e. less severe than type I
 Investigations of indirect
hyperbilirubinemia
Total bilirubin & direct fraction (direct fraction is below 15 %
of total)
Coomb's test: -If positive-- blood group of infant & mother.
Hemoglobin value: -If high-- polycythemia.
If normal or low {<13gm/dl) --check reticulocyte count.
Reticulocyte count: - Normal --extravascular hemorrhage.
High(> 6%) --Check RBCs shape & osmotic fragility
-- G6PD enzyme assay.
Others - Serum T4 & TSH for hypothyroid.
-Phenobarbitone trial for Criggler-Najjar type II.
 Treatment of indirect hyperbilirubinemia

• 1. Phototherapy
Indications: 1- Rise of bilirubin Below the critical levels.
- In healthy full term  at 15-20 mg/dl.
- In preterm and sick neonates  at lower levels.
2- During waiting for exchange transfusion.
3- Prophylactic in: - Very low birth weight.
- Severely bruised neonates.
- Immediate after birth if Rh incompatibility
is suspected
• Avoided - In direct hyperbilirubinemia 
Bronzed baby syndrome
• Exposure to blue or white light with wave
length 425- 475nm
• convert insoluble unconguated bilirubin to
non toxic, soluble forms by
photoisomerization & photooxidation 
execreted in bile & urine
 Side effects
• Loose stool due to excretion ofbile salts &
unconjugated bile
• Skin rash and tanning of skin
• Hyperthermia or hypothermia
• Dehydration due to insensible water loss
• Damage to exposed eye or genitalia.
• Upset maternal - infant interaction
 2 . Exchange transfusion
• Indications 1- In Rh-incompatibility:
- Cord bilirubin > 5 mgldl(normally <3 mg/dl)
- Cord hemoglobin < 1 0 gm/dl.
-Rapid rise of bilirubin(> 1 mgldl/hour)
despite phototherapy.
- Bilirubin level exceeding:
- 1 0 mg/dl at first day.
- 15 mg/dl at second day.
- 20 mg/dl at any time.
-History of kernicterus in a sibling.
2- In other causes: if serum bilirubin exceeds
critical values:
-Healthy full term> 20 mg/dl(some consider
it above25 mg/dl.)
- Preterm and sick neonates --+ at lower
levels.
• - Remove excess unconjugated lipid soluble
bilirubin.
• -Correct anemia
• - Remove antibodies from the circulation
• - Provide albumin
• Procedure
• -Blood used is:
* 0 negative compatible with both maternal and
neonatal blood
* Fresh, warm.
* Amount= double the neonate blood volume (2x80
mllkg).
• -Small amounts (10-20 ml) are removed and replaced
by equal amounts of the new blood.
• - I.V Glucose and calcium gluconate are given at 100 ml
blood intervals
• Drawback
-Of umbilical catheterization e.g. embolism,
thrombosis, sepsis & portal hypertension in
later life.
-Heart failure (volume overload on the heart).
-Hazards of blood transfusion.
- Hypocalcaemia, hypoglycaemia, hyperkalemia
Indications for exchange transfusion other than
hyperbilirubinemia:
1- Neonatal sepsis.
2- Necrotizing enterocolitis.
3- Anemic heart failure --+ use packed RBCs.
4- Respiratory distress syndrome.
5- Congenital cyanotic heart diseases with marked
polycythemia --+ use plasma
6- Sickle all anemia Crises.
• 3. Special Cases
• Intra venous immunoglobulin
- Can reduce rate of hemolysis and need for
exchange transfusion in ABO and Rh
incompatibility
- Dose : 0.5-1 gmlkg /dose repeat in 12 hours
• Criggler Najjar Syndrome type II
- Phenobarbitone 5 mglkg/d oral.
-Role: Stimulates glucoronyl transferase
enzyme( enzyme inducer).
- Side effect: sedation ~ poor feeding
* Criggler Najjar Syndrome type I
- Repeated exchange transfusion &
phototherapy to keep bilirubin < 20 mgldl in 1st
2-4 weeks.
- Oral agar block enterohepatic circulation of
bilirubin.
- Metalloporphyrinblock heme oxygenase.
-Hepatic transplantation, gene therapy & enzyme
replacement are future therapies
• Breast milk jaundice
- Stop breast feeding for 48 hours (jaundice will
disappear and not recur).
• * Treatment of the cause
- Treat hypothyroidism.
- Avoid drugs which displace bilirubin from
plasma protein binding sites.
- Avoid steroids( competitive inhibition of
glucoronyl transferase enzyme)
 Conjugated Hyperbilirubinemia
• Definition: Rise of total serum bilirubin with
the conjugated fraction> 15% of total or > 2
mg/dl.
• Cholestasis: retention of conjugated bilirubin
as well as other constituents of bile (e.g. bile
salts)
 Causes
• A).Defective secretion of conjugated bilirubin
by hepatocytes
a .Genetic -Rotor and Dubin Johnson
syndrome
- Bile acid synthesis defects
-Progressive familial intrahepatic
cholestasis (PFIC)
b. Acquired: (Neonatal hepatitis) due to:
* Infections : - TORCH.
-Sepsis.
- Viral hepatitis :Echo,Herpes,Ebstein
Barr, Rarely HBV, HCV.
- Idiopathic hepatitis
*Metabolic: - a 1 antitrypsin deficiency
- Galactosemia
- Tyrosinemia
2.Defective excretion due to bile flow obstruction
a. Intrahepatic:
- Congenital intrahepatic biliary atresia.
- Intrahepatic biliary paucity (hypoplasia) e.g.
Allagile syndrome
b. Extrahepatic:
- Congenital extrahepatic biliary atresia.
- Inspissated bile syndrome (Bile plug); may
follow severe hemolytic attack.
- Biliary stones or tumours
 Clinical features

• Color of sclera : olive green.

Color of urine : dark (bilirubinuria).
Color of stool :pale (or clay).
• Possible concurrent associations:
-Hepatosplenomegaly.
- Liver cells dysfunction.
- Malabsorption and failure to thrive
- Underlying systemic disease e.g. sepsis,
TORCH, inborn error of metabolism
- No risk of kernicterus.
• Timing of appearance of jaundice
* In 1st day of life - TORCH infection
( or in the 1st week)
* Late in the 1st week of life - Neonatal sepsis
* Persistent during 1st month -Neonatal
hepatitis (metabolic or infections )
- Congenital biliary atresia.
- Inspissated bile syndrome
 Investigations

-Liver function tests.

- Liver scan (HIDA scan).
- Liver biopsy.
- Metabolic screen for inborn errors of
metabolism.
- TORCH screen.
- Sepsis screen.
 Treatment

a. Curable causes
- Sepsis : antibiotics.
- Galactosaemia : lactose free milk.
-Extra hepatic biliary atresia: Kasai operation ( hepato-porto-
enterostomy)
b. Supportive
-Formula with medium chain triglycerides.
- Fat soluble vitamins.
-Water soluble vitamines
- Chloretics e.g. urso deoxy cholic acid
-Bile acid binders (Cholestyramine) oral ~..1-serum chlosterol & bile acids.
- Minerals (calcium, phosphate, zinc).
- Liver transplantation for end stage liver failure.
 Kernicterus
• Definition
• Yellowish staining of the cerebellar & cerebral nuclei
(especially basal ganglia) due to deposition of
unconjugated bilirubin resulting in neuronal necrosis.
• Etiology
• 1- Level of serum unconjugated bilirubin exceeding
critical values
-> 1 0 mg/dl in 1st day
-> 15 mg/dl in 2"d day
-> 25 mg/dl afterwards.
• kernicterus may occur at a lower levels in
presence of risk factors :
a.Increase blood brain barrier permeability
-Prematurity & low birth weight
- Acidosis
-Sepsis
-Hypoxia
-Anemia
• b. Displace bilirubin from albumin:
-Drugs (ampicillin, sulpha, aspirin)
- Hypothermia
-Hypoalbuminemia
The longer the duration the more risk of
kernicterus
• Clinical picture
• 1. Acute bilirubin encephalopathy : passes in 3 phases:
• Phase 1: In the 1st – 2nd days
- Poor suckling, lethargy, loss of Moro reflex
- Hypotonia and seizures
-Apnea
Phase 2: In the middle of the 1 week
- Hypertonia, opisthotonos
-Fever
- High pitched cry
Phase 3 : After the 1st week
- Hypertonia and stiffness
• 2. Lucid interval: Survivors from previous phase go into
lucid interval for few months  there's apparent
recovery or few symptoms.
• 3. Chronic bilirubin encephalopathy: Picture of
Cerebral Palsy:
* Type : chorio asthetoid or spastic.
* Associations: - Mental retardation.
- Sensorineural deafness.
-Squint & upward gase plasy.
- Defective speech.
- Recurrent convulsions.
 Management

• a- Prophylaxis:
* Treatment of indirect hyperbilirubinemia
* Prevention of other risk factors: e.g. sepsis,
acidosis, hypoxia, .....
• b- Treatment of established cases: not curable,
need only supportive treatment for cerebral
palsy.