Hyperemesis gravidarum

Hyperemesis gravidarum (HG) is a pregnancy complication that is characterized

Hyperemesis gravidarum
by severe nausea, vomiting, weight loss, and possibly dehydration.[1] Signs and
symptoms may also include vomiting several times a day and feeling faint.[2] Specialty Gynecology
Hyperemesis gravidarum is considered more severe than morning sickness.[2] Often Symptoms Nausea and vomiting
symptoms get better after the 20th week of pregnancy but may last the entire such that weight loss
pregnancy duration.[2] and dehydration
occur[1]
The exact causes of hyperemesis gravidarum are unknown.[3] Risk factors include
Duration Often gets better but
the first pregnancy, multiple pregnancy, obesity, prior or family history of HG,
may last entire
trophoblastic disorder, and a history of eating disorders.[3][4] Diagnosis is usually
pregnancy[2]
made based on the observed signs and symptoms.[3] HG has been technically
defined as more than three episodes of vomiting per day such that weight loss of 5% Causes Unknown[3]
or three kilograms has occurred and ketones are present in the urine.[3] Other Risk First pregnancy,
potential causes of the symptoms should be excluded including urinary tract factors multiple pregnancy,
infection and high thyroid levels.[5] obesity, prior or family
history of hyperemesis
Treatment includes drinking fluids and a bland diet.[2] Recommendations may
gravidarum,
include electrolyte-replacement drinks, thiamine, and a higher protein diet.[3][7]
trophoblastic disorder,
Some women require intravenous fluids.[2] With respect to medications pyridoxine
history of an eating
or metoclopramide are preferred.[5] Prochlorperazine, dimenhydrinate, or
disorder[3][4]
ondansetron may be used if these are not effective.[3][5] Hospitalization may be
Diagnostic Based on symptoms[3]
required.[3] Psychotherapy may improve outcomes.[3] Evidence for acupressure is
method
poor.[3]
Differential Urinary tract infection,
While vomiting in pregnancy has been described as early as 2,000 BC, the first clear diagnosis high thyroid levels[5]
medical description of hyperemesis gravidarum was in 1852 by Antoine Dubois.[8]
Treatment Drinking fluids, bland
Hyperemesis gravidarum is estimated to affect 0.3–2.0% of pregnant women.[6]
diet, intravenous
While previously known as a common cause of death in pregnancy, with proper
fluids[2]
treatment this is now very rare.[9][10] Those affected have a low risk of miscarriage
but a higher risk of premature birth.[4] Some pregnant women choose to have an Medication Pyridoxine,
abortion due to HG's symptoms.[7] metoclopramide[5]
Frequency ~1% of pregnant
women[6]

Contents
Signs and symptoms
Causes
Pathophysiology
Diagnosis
Differential diagnosis
Investigations
Management
Intravenous fluids
Medications
Nutritional support
Alternative medicine
 Complications
Pregnant woman
Infant
Epidemiology
History
Etymology
Notable cases
References
External links

Signs and symptoms

[11]
When vomiting is severe it may result in the following:

Loss of 5% or more of pre-pregnancybody weight

Dehydration, causing ketosis,[12] and constipation
Nutritional disorders such as vitamin B1 (thiamine) deficiency, vitamin B6 deficiency or vitamin B12 deficiency
Metabolic imbalances such as metabolicketoacidosis[11] or thyrotoxicosis[13]
Physical and emotionalstress of pregnancy on the body
Difficulty with activities of daily living
Symptoms can be aggravated by hunger, fatigue, prenatal vitamins (especially those containing iron), and diet.[14] Many people with
HG are extremely sensitive toodors in their environment; certain smells may exacerbate symptoms. Excessive salivation, also known
as sialorrhea gravidarum, is another symptom experienced by some women.

Hyperemesis gravidarum tends to occur in the first trimester of pregnancy[12] and lasts significantly longer than morning sickness.
While most women will experience near-complete relief of morning sickness symptoms near the beginning of their second trimester,
some sufferers of HG will experience severe symptoms until they give birth to their baby, and sometimes even after giving birth.[15]

A small percentage rarely vomit, but the nausea still causes most (if not all) of the same issues that hyperemesis with vomiting does.

Causes
There are numerous theories regarding the cause of HG, but the cause remains controversial. It is thought that HG is due to a
combination of factors which may vary between women and include genetics.[11] Women with family members who had
[16]
Hyperemesis are more likely to develop the disease.

One factor is an adverse reaction to the hormonal changes of pregnancy, in particular, elevated levels of beta human chorionic
gonadotropin (hCG).[17][18] This theory would also explain why hyperemesis gravidarum is most frequently encountered in the first
trimester (often around 8–12 weeks of gestation), as hCG levels are highest at that time and decline afterward. Another postulated
cause of HG is an increase in maternal levels of estrogens (decreasing intestinal motility and gastric emptying leading to
nausea/vomiting).[11]

Pathophysiology
Although the pathophysiology of HG is poorly understood, the most commonly accepted theory suggests that levels of hCG are
associated with it.[5] Leptin may also play a role.[19]

[20]
Possible pathophysiological processes involved are summarized in the following table:
 Source Cause Pathophysiology

Distention of
Placenta gastrointestinal tract
hCG Crossover with TSH,
Corpus
luteum causing gestational
thyrotoxicosis[5]

Decreased gut
mobility
Elevated liver
enzymes
Morning sickness
Estrogen Decreased lower
Placenta esophageal
Progesterone
sphincter pressure
Increased levels of
sex steroids in
hepatic portal
system[21]

Gastrointestinal Helicobacter Increased steroid levels

tract pylori in circulation[22]

Diagnosis
Hyperemesis gravidarum is considered a diagnosis of exclusion.[11] HG can be associated with serious problems in the mother or
baby, such as Wernicke's encephalopathy, coagulopathy, peripheral neuropathy.[5]

Women experiencing hyperemesis gravidarum often are dehydrated and lose weight despite efforts to eat.[23][24] The onset of the
.[11]
nausea and vomiting in hyperemesis gravidarum is typically before the twenty-second week of pregnancy

Differential diagnosis
Diagnoses to be ruled out include the following:[20]
 Type Differential diagnoses

Infections Urinary tract infection

(usually accompanied by fever or associated neurological Hepatitis
symptoms) Meningitis
Gastroenteritis

Appendicitis
Gastrointestinal disorders Cholecystitis
Pancreatitis
(usually accompanied by abdominal pain)
Fatty liver
Peptic ulcer
Small bowel obstruction

Thyrotoxicosis (common in Asian

subcontinent)[5]
Metabolic Addison's disease
Diabetic ketoacidosis
Hyperparathyroidism

Drugs Antibiotics
Iron supplements

Gestational trophoblastic diseases (rule out with urine β-hCG) Molar pregnancy
choriocarcinoma

Investigations
Common investigations include blood urea nitrogen (BUN) and electrolytes, liver function tests, urinalysis,[24] and thyroid function
tests. Hematological investigations include hematocrit levels, which are usually raised in HG.[24] An ultrasound scan may be needed
.[25]
to know gestational status and to exclude molar or partial molar pregnancy

Management
Dry bland food and oral rehydration are first-line treatments.[26] Due to the potential for severe dehydration and other complications,
HG is treated as an emergency. If conservative dietary measures fail, more extensive treatment such as the use of antiemetic
medications and intravenous rehydration may be required. If oral nutrition is insufficient, intravenous nutritional support may be
needed.[12] For women who require hospital admission, thromboembolic stockingsor low-molecular-weight heparin may be used as
measures to prevent the formation of a blood clot.[20]

Intravenous fluids
Intravenous (IV) hydration often includes supplementation of electrolytes as persistent vomiting frequently leads to a deficiency.
Likewise, supplementation for lost thiamine (Vitamin B1) must be considered to reduce the risk of Wernicke's encephalopathy.[27] A
and B vitamins are depleted within two weeks, so extended malnutrition indicates a need for evaluation and supplementation. In
addition, electrolyte levels should be monitored and supplemented; of particular concern are
sodium and potassium.

After IV rehydration is completed, patients in general progress to frequent small liquid or bland meals. After rehydration, treatment
focuses on managing symptoms to allow normal intake of food. However, cycles of hydration and dehydration can occur, making
continuing care necessary. Home care is available in the form of a PICC line for hydration and nutrition (called total parenteral
nutrition).[28] Home treatment is often less expensive than long-term or repeated hospitalizations.
Medications
A number of antiemetics are effective and safe in pregnancy including: pyridoxine/doxylamine, antihistamines (such as
diphenhydramine), and phenothiazines (such as promethazine).[29] With respect to effectiveness, it is unknown if one is superior to
another for relieving nausea or vomiting.[29] Limited evidence from published clinical trials suggests the use of medications to treat
hyperemesis gravidarum.[30]

While pyridoxine/doxylamine, a combination of vitamin B6 and doxylamine, is effective in nausea and vomiting of pregnancy,[31]
some have questioned its effectiveness in HG.[32] Ondansetron may be beneficial, however, there are some concerns regarding an
association with cleft palate,[33] and there is little high-quality data.[29] Metoclopramide is also used and relatively well tolerated.[34]
Evidence for the use of corticosteroids is weak; there is some evidence that corticosteroid use in pregnant women may slightly
increase the risk of oral facial clefts in the infant and may suppress fetal adrenal activity.[11][35] However, hydrocortisone and
[11]
prednisolone are inactivated in the placenta and may be used in the treatment of hyperemesis gravidarum after 12 weeks.

Nutritional support
Women not responding to IV rehydration and medication may require nutritional support. Patients might receive parenteral nutrition
(intravenous feeding via a PICC line) or enteral nutrition (via anasogastric tube or a nasojejunal tube). There is only limited evidence
from trials to support the use of vitamin B6 to improve outcome.[30] Hyperalimentation may be necessary in certain cases to help
maintain volume requirements and allow weight gain.[25] A physician might also prescribe Vitamin B1 (to prevent Wernicke's
encephalopathy) and folic acid supplementation.[20]

Alternative medicine
Acupuncture (both with P6 and traditional method) has been found to be ineffective.[30] The use of ginger products may be helpful,
but evidence of effectiveness is limited and inconsistent, though three recent studies support ginger overplacebo.[30]

Complications

Pregnant woman
If HG is inadequately treated, anemia,[11] hyponatremia,[11] Wernicke's encephalopathy,[11] kidney failure, central pontine
myelinolysis, coagulopathy, atrophy, Mallory-Weiss tears,[11] hypoglycemia, jaundice, malnutrition, pneumomediastinum,
rhabdomyolysis, deconditioning, deep vein thrombosis, pulmonary embolism, splenic avulsion, or vasospasms of cerebral arteries are
possible consequences. Depression and PTSD [36] are common secondary complications of HG and emotional support can be
beneficial.[11]

Infant
The effects of HG on the fetus are mainly due to electrolyte imbalances caused by HG in the mother.[20] Infants of women with
severe hyperemesis who gain less than 7 kg (15.4 lb) during pregnancy tend to be of lower
birth weight, small for gestational age, and
born before 37 weeks gestation.[12] In contrast, infants of women with hyperemesis who have a pregnancy weight gain of more than
7 kg appear similar to infants from uncomplicated pregnancies.[37] There is no significant difference in the neonatal death rate in
infants born to mothers with HG compared to infants born to mothers who do not have HG.[11] Children born to mothers with
[38]
undertreated Hyperemesis have a fourfold increase in neurobehavioral diagnoses.

Epidemiology
Vomiting is a common condition affecting about 50% of pregnant women, with another 25% having nausea.[39] However, the
incidence of HG is only 0.3–1.5%.[5] After preterm labor, hyperemesis gravidarum is the second most common reason for hospital
admission during the first half of pregnancy.[11] Factors such as infection with Helicobacter pylori, a rise in thyroid hormone
production, low age, low body mass index prior to pregnancy, multiple pregnancies, molar pregnancies, and a past history of
[11]
hyperemesis gravidarum have been associated with the development of HG.

History
Thalidomide was prescribed for treatment of HG in Europe until it was recognized that thalidomide is teratogenic and is a cause of
phocomelia in neonates.[40]

Etymology
Hyperemesis gravidarum is from the Greek hyper-, meaning excessive, andemesis, meaning vomiting, and the Latin gravidarum, the
feminine genitive plural form of an adjective, here used as a noun, meaning "pregnant [woman]". Therefore, hyperemesis gravidarum
means "excessive vomiting of pregnant women".

Notable cases
Author Charlotte Brontë is often thought to have suffered from hyperemesis gravidarum. She died in 1855 while four months
pregnant, having been afflicted by intractable nausea and vomiting throughout her pregnancy, and was unable to tolerate food or even
water.[41]

Catherine, Duchess of Cambridge, was hospitalised due to hyperemesis gravidarum during her first pregnancy, and was treated for a
similar condition during the subsequent two.[42][43]

.[44]
The Saturdays singer Frankie Bridge had hyperemesis gravidarum during her second pregnancy

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External links
Classification ICD-10: V·T·D
O21.1 · ICD-9-CM:
643.1
External MedlinePlus:
resources 001499

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