Hyperemesis gravidarum

Hyperemesis gravidarum (HG) is a complication of pregnancy that is characterized by severe nausea and vomiting such that weight loss and dehydration occur.^[1] Signs and symptoms may include vomiting several times a day and feeling faint. It is more severe than morning sickness. Often symptoms get better after the 20th week of pregnancy but may last the entire pregnancy.^[2]

The exact cause of hyperemesis gravidarum is not known.^[3] Risk factors include the first pregnancy, multiple pregnancy, obesity, prior or family history of hyperemesis gravidarum, trophoblastic disorder, and a history of an eating disorder.^[3][4] The diagnosis is usually made based on the signs and symptoms. It has been technically defined as more than three episodes of vomiting per day such that weight loss of 5% or three kilograms has occurred and ketones are present in the urine.^[3] Other potential causes of the symptoms should be excluded including urinary tract infection and high thyroid levels.^[5]

Treatment includes drinking fluids and a bland diet.^[2] Recommendations may include electrolyte-replacement drinks, thiamine, and a higher protein diet.^[3][6] Some women require intravenous fluids.^[2] With respect to medications pyridoxine or metoclopramide are preferred.^[5] Prochlorperazine, dimenhydrinate, or ondansetron may be used if these are not effective.^[3][5] Hospitalization may be required. Psychotherapy may improve outcomes. Evidence for acupressure is poor.^[3]

While vomiting in pregnancy has been described as early as 2,000 BC, the first clear medical description of hyperemesis gravidarum was in 1852 by Antoine Dubois.^[7] Hyperemesis gravidarum is estimated to affect 0.3–2.0% of pregnant women.^[8] While previously a common cause of death in pregnancy, with proper 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 women opt to have an abortion because of the symptoms.^[6]

Signs and symptoms

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

• Loss of 5% or more of pre-pregnancy body 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 metabolic ketoacidosis^[11] or thyrotoxicosis^[13]
• Physical and emotional stress 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 to odors in their environment; certain smells may exacerbate symptoms. This is known as hyperolfaction. Ptyalism, or hypersalivation, is another symptom experienced by some women suffering from HG.

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 Hyperemesis are more likely to develop the disease.^[16]

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

Morning sickness

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]

Possible pathophysiological processes involved are summarized in the following table:^[20]

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 nausea and vomiting in hyperemesis gravidarum is typically before the twenty-second week of pregnancy.^[11]

Differential diagnosis

Diagnoses to be ruled out include the following:^[20]

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 to know gestational status and to exclude molar or partial molar pregnancy.^[25]

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 stockings or 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,^[29] and there is even limited evidence of significant effect at all of pharmacological therapy in 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 prednisolone are inactivated in the placenta and may be used in the treatment of hyperemesis gravidarum after 12 weeks.^[11]

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 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][36] The use of ginger products may be helpful, but evidence of effectiveness is limited and inconsistent, though two recent studies support ginger over placebo.^[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 ^[37] 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.^[38] 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 undertreated Hyperemesis have a fourfold increase in neurobehavioral diagnoses.^[39]

Epidemiology

Vomiting is a common condition affecting about 50% of pregnant women, with another 25% having nausea.^[40] 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 hyperemesis gravidarum have been associated with the development of HG.^[11]

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.^[41]

Etymology

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 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.^[42]

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

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

References