Hyperemesis gravidarum

Hyperemesis gravidarum (HG) is a

When vomiting is severe, it may result in the following:[16]

• Loss of 5% or more of pre-pregnancy
  body weight
• Dehydration, causing ketosis,^[17] and constipation
• vitamin B₆ (pyridoxine) deficiency or vitamin B₁₂ (cobalamin) deficiency
• thyrotoxicosis^[18]
• Physical and emotional stress
• Difficulty with activities of daily living

Symptoms can be aggravated by

A small percentage rarely vomit, but the nausea still causes most (if not all) of the same issues that hyperemesis with vomiting does.[21]

Complications

Pregnant woman

Failure to treat, or inadequate treatment of HG can lead to one or more of the following:^[16]

• anemia
• hyponatremia
• Wernicke's encephalopathy
• kidney failure
• central pontine myelinolysis
• coagulopathy
• atrophy
• Mallory–Weiss tears
• hypoglycemia
• jaundice
• malnutrition
• pneumomediastinum
• rhabdomyolysis
• deconditioning
• deep vein thrombosis
• pulmonary embolism
• splenic avulsion
• vasospasms of cerebral arteries

Depression and post-traumatic stress disorder are common secondary complications of HG, and emotional support can be beneficial.^[16][22]

Infant

The effects of HG on the fetus are mainly due to electrolyte imbalances caused by HG in the mother.^[23] Women with severe hyperemesis who gain less than 7 kilograms (15 lb) during pregnancy tend have newborns with lower birth weight or are smaller for gestational age. They also tend to give birth before 37 weeks gestation.^[17]

In contrast, infants of women with hyperemesis who have a pregnancy weight gain of more than 7 kilograms (15 lb) appear similar to infants from uncomplicated pregnancies.^[24] 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.^[16] Children born to mothers with undertreated HG have a fourfold increase in neurobehavioral diagnoses.^[25]

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.^[16] Women with family members who had HG are more likely to develop the disease.^[26]

One factor is an

In 2020, another possible cause of HG was published by a research team led by Marlena Fejzo, a medical researcher whose interest was kindled by her then-doctor telling her that her severe vomiting was "just a ploy to gain sympathy and attention":^[29] "Evidence suggests abnormal levels of the hormone GDF15 are associated with HG. The validation of a second risk variant, rs1054221, provides further support for GDF15's role in the etiology of HG. Additionally, maternal genes appear to play a more significant role than paternal DNA in contributing to the severity of NVP."^[30]

In a 2023 study, Fejzo further linked GDF15 as cause when present in high levels due to fetal cell production in contrast with the natural low levels which result maternal sensitivity.^[31][32][33]

Pathophysiology

Although the

Possible pathophysiological processes involved are summarized in the following table:[23]

Diagnosis

Hyperemesis gravidarum is considered a diagnosis of exclusion.^[16][37] Criteria for diagnosing HG in a patient generally includes vomiting that results in significant dehydration and weight loss (at least 5% of the patients pre-pregnancy weight). Urinalysis is usually preformed and blood samples may be taken to check for ketonuria, electrolyte imbalances, and complete blood counts, all of which could indicate HG or prompt an alternative diagnosis.^[38]

Women experiencing hyperemesis gravidarum often are dehydrated and lose weight despite efforts to eat.^[39][40] Similar to the onset of standard bouts of morning sickness, the nausea and vomiting with hyperemesis typically starts between 5 and 6 weeks into pregnancy.^[41]

Differential diagnosis

Diagnoses to be ruled out include the following:^[23]

Investigations

Common investigations include

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.^[45] Home treatment is often less expensive and reduces the risk for a hospital-acquired infection compared with long-term or repeated hospitalizations.

Medications

A number of antiemetics are effective and safe in pregnancy including:

Ondansetron may be beneficial, however, there are some concerns regarding an association with cleft palate,^[50] and there is little high-quality data.^[46] Metoclopramide is also used and relatively well tolerated.^[48] Evidence for the use of corticosteroids is weak; there is some evidence that corticosteroid use in pregnant women may slightly increase the risk of cleft lip and cleft palate in the infant and may suppress fetal adrenal activity.^[16][51] However, hydrocortisone and prednisolone are inactivated in the placenta and may be used in the treatment of hyperemesis gravidarum after 12 weeks.^[16]

Medicinal cannabis has been used to treat pregnancy-associated hyperemesis.^[52]

Nutritional support

Women not responding to IV rehydration and medication may require nutritional support. Patients might receive

Hyperemesis gravidarum is from the Greek 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 while four months pregnant, having been affected by intractable nausea and vomiting throughout her pregnancy, and was unable to tolerate food or even water.^[55]

Catherine, Princess of Wales was hospitalised due to hyperemesis gravidarum during her first pregnancy, and was treated for a similar condition during the subsequent two.^[56][57]

Comedienne Amy Schumer cancelled the remainder of a tour due to hyperemesis gravidarum.^[58]

Society and culture

In previous centuries, the cause was unknown, and various false claims were made, such as the 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.^[29] These erroneous beliefs led to various abusive practices, such as isolating them from their friends and family, or leaving severely ill women to lie in the vomit when they were too weak to clean themselves, which have since been condemned by healthcare professionals and medical organizations such as the College of French Gynecologists and Obstetricians.^[29][59] The HER Foundation is grassroots network of HG survivors and experts.^[60]

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,