Hyperemesis gravidarum ( HG) is a pregnancy complication that is characterized by severe nausea, vomiting, weight loss, and possibly dehydration.[ It is considered a more severe form of morning sickness.][ Symptoms often get better after the 20th week of pregnancy but may last the entire pregnancy duration.]
The exact causes of hyperemesis gravidarum are unknown.[ Risk factors include the first pregnancy, multiple pregnancy, obesity, prior or family history of HG, and trophoblastic disorder. A December 2023 study published in Nature indicated a link between HG and abnormally high levels of the hormone GDF15, as well as increased sensitivity to that specific hormone.]
Diagnosis is usually made based on the observed signs and symptoms.
Treatment includes drinking fluids and a bland diet.[ Recommendations may include electrolyte-replacement drinks, thiamine, and a higher protein diet.][ With respect to medications, pyridoxine or metoclopramide are preferred.][ Prochlorperazine, dimenhydrinate, ondansetron (sold under the brand-name Zofran) or corticosteroids may be used if these are not effective.][ Hospitalization may be required due to the severe symptoms associated.][ Psychotherapy may improve outcomes.][ Evidence for acupressure is poor.][
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While vomiting in pregnancy has been described as early as 2,000 BCE, the first clear medical description of HG was in 1852, by Paul Antoine Dubois.[
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Signs and symptoms
When vomiting is severe, it may result in the following:
Symptoms can be aggravated by hunger, fatigue, prenatal vitamins (especially those containing iron), and diet.
Hyperemesis gravidarum tends to occur in the first trimester of pregnancy
A small percentage rarely vomit, but the nausea still causes most (if not all) of the same issues that hyperemesis with vomiting does.
Complications
Pregnant woman
Failure to treat or inadequate treatment of HG can lead to one or more of the following:
Depression and post-traumatic stress disorder are common secondary complications of HG, and emotional support can be beneficial.
Infant
The effects of HG on the fetus are mainly due to electrolyte imbalances caused by HG in the mother.
In contrast, infants of women with hyperemesis who have a pregnancy weight gain of more than appear similar to infants from uncomplicated pregnancies.
Causes
Though the exact cause of HG is unknown, there are numerous theories. It is thought that HG is caused by a combination of factors, many of which may vary between women, some of which include a genetic predisposition.
One factor is an adverse effect to the hormonal changes of pregnancy, in particular, elevated levels of beta human chorionic gonadotropin (β-hCG).
Pathophysiology
Although the pathophysiology of HG is unclear, one of the most commonly accepted theories suggests that levels of β-hCG are associated with it.[ Leptin, a hormone that inhibits hunger, may also play a role.]
Possible pathophysiological processes involved are summarized in the following table:
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Distention of the gastrointestinal tract
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Crossover with TSH, causing gestational thyrotoxicosis
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Decreased gut mobility
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Elevated liver enzymes
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Decreased lower esophageal sphincter pressure
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Increased levels of sex steroids in hepatic portal system
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Helicobacter pylori
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Gastroesophageal reflux disease (GERD)
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Increased steroid levels in circulation
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Relaxing of the lower esophagal sphincter
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Diagnosis
Hyperemesis gravidarum is considered a diagnosis of exclusion.
Women experiencing hyperemesis gravidarum often are dehydrated and lose weight despite efforts to eat.
Differential diagnosis
Diagnoses to be ruled out include the following:|
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| Infections
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| Gastrointestinal disorders
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Thyrotoxicosis (common in Asian subcontinent)
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Addison's disease
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Diabetic ketoacidosis
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Hyperparathyroidism
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Investigations
Common investigations include blood urea nitrogen (BUN) and electrolytes, liver function tests, urinalysis,
Management
Dry, bland food and oral rehydration are first-line treatments.
Intravenous fluids
Intravenous (IV) hydration often includes supplementation of 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.
After IV rehydration is completed, patients typically begin to tolerate 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 peripherally inserted central catheter (PICC) line for hydration and nutrition.
Medications
Several antiemetics are effective and safe in pregnancy including: pyridoxine/doxylamine, antihistamines (such as diphenhydramine), and phenothiazines (such as promethazine).[ Limited evidence from published clinical trials suggests the use of medications to treat hyperemesis gravidarum.]
While pyridoxine/doxylamine, a combination of vitamin B6 and doxylamine, is effective in nausea and vomiting of pregnancy,
Ondansetron may be beneficial, however, there are some concerns regarding an association with cleft palate,
Medicinal cannabis has been used to treat pregnancy-associated hyperemesis.
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 a nasogastric tube or a nasojejunal tube). There is only limited evidence from trials to support the use of vitamin B6 to improve outcomes.
Alternative medicine
Acupuncture (both with P6 and traditional method) is ineffective.
Epidemiology
Vomiting is a common condition affecting about 50% of pregnant women, with another 25% having nausea.[ After preterm labor, hyperemesis gravidarum is the second most common reason for hospital admission during the first half of pregnancy.]
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.
Etymology
Hyperemesis gravidarum is from the Greek language hyper-, meaning excessive, and emesis, 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 had hyperemesis gravidarum. She died in 1855 four months pregnant, having been affected by intractable nausea and vomiting throughout her pregnancy and was unable to tolerate food or even water.
Catherine, Princess of Wales was hospitalised due to hyperemesis gravidarum during her first pregnancy, and was treated for the same condition during the subsequent two.
Comedienne Amy Schumer cancelled the remainder of a tour due to hyperemesis gravidarum.
Society and culture
In previous centuries, the cause was unknown, and various false claims were made, such as severe vomiting being caused by the woman's rejection of femininity, a manifestation of a subconscious desire to terminate the pregnancy, or being an attention-seeking behavior.
Hyperemesis gravidarum is estimated to cost US$3 billion per year for hospitalization costs alone, not including the direct medical costs of additional outpatient medical appointments, prescription drugs, and home health care, or any indirect costs such as lost work.
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