Hyperemesis gravidarum

Hyperemesis gravidarum (HG) is a severe form of morning sickness, with "unrelenting, excessive pregnancy-related nausea and/or vomiting that prevents adequate intake of food and fluids." Hyperemesis is considered a rare complication of pregnancy but, because nausea and vomiting during pregnancy exist on a continuum, there is often not a good diagnosis between common morning sickness and hyperemesis. Estimates of the percentage of pregnant women afflicted range from 0.3% to 2.0%.

Etymology
Hyperemesis gravidarum is from the Greek hyper-, meaning excessive, and emesis, meaning vomiting, as well as the Latin gravida, meaning pregnant. Therefore, hyperemesis gravidarum means "excessive vomiting in pregnancy."

Causes
The cause of HG is unknown. The leading theories state that it is an adverse reaction to the hormonal changes of pregnancy. In particular Hyperemesis may be due to raised levels of beta HCG (human chorionic gonadotrophin) as it is more common in multiple pregnancies and in gestational trophoblastic disease. This theory would also explain why hyperemesis gravidarum is most frequently encountered in first trimester (often around 8 – 12 weeks of gestation), as HCG levels are highest at that time and decline afterwards. It is thought that estrogen produces nausea and regurgitation of stomach acids in some women. There is also evidence that leptin may play a role in HG.

A recent study gives "preliminary evidence" that there may be a genetic component.

Women experiencing their first pregnancy, or who have a relatively high body weight, or are relatively affluent white women, are at an increased risk for HG. It has also been found to develop frequently in women who are young, unmarried and dependent. Some investigators speculate that, at least in some instances, there may be psycho-social factors influencing the development of HG.

Symptoms of morning sickness, and HG, can be aggravated by the following factors: hunger, fatigue, prenatal vitamins (especially those containing iron), odors, and diet.

Symptoms
When HG is severe and/or inadequately treated, it may result in:
 * Loss of 5% or more of pre-pregnancy body weight
 * Dehydration, causing ketosis and constipation
 * Nutritional deficiencies
 * Metabolic imbalances
 * Altered sense of taste
 * Sensitivity of the brain to motion
 * Food leaving the stomach more slowly
 * Rapidly changing hormone levels during pregnancy
 * Stomach contents moving back up from the stomach
 * Physical and emotional stress of pregnancy on the body
 * Subconjunctival hemorrhage (broken blood vessels in the eyes)
 * Difficulty with daily activities
 * Hallucinations

Some women with HG lose as much as 30% of their body weight. Many sufferers of 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.

As compared to morning sickness, HG tends to begin somewhat earlier in the pregnancy and last significantly longer. 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. An overview of the significant differences between morning sickness and HG can be found at Hyperemesis or Morning Sickness: Overview.

For the pregnant woman
If inadequately treated, HG can cause renal failure, central pontine myelinolysis, coagulopathy, atrophy, Mallory-Weiss syndrome, hypoglycemia, jaundice, malnutrition, Wernicke's encephalopathy, pneumomediastinum, rhabdomyolysis, deconditioning, splenic avulsion, and vasospasms of cerebral arteries. Depression is a common secondary complication of HG. On rare occasions a woman can die from hyperemesis; Charlotte Bronté is a presumed victim of the disease.

For the fetus
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, in contrast, infants of women with hyperemesis who have a pregnancy weight gain of more than 7 kg appear similar as infants from uncomplicated pregnancies. No long-term follow-up studies have been conducted on children of hyperemetic women.

Diagnosis
Women who are experiencing hyperemesis gravidarum often are dehydrated and losing weight despite efforts to eat. The nausea and vomiting begins in the first or second month of pregnancy. It is extreme and is not helped by normal measures.

Fever, abdominal pain, or late onset of nausea and vomiting usually indicate another condition, such as appendicitis, gallbladder disorders, gastritis, hepatitis, or infection.

Treatment
Because of the potential for severe dehydration and other complications, HG is generally treated as a medical emergency. Treatment of HG may include antiemetic medications and intravenous rehydration. If medication and IV hydration are insufficient, nutritional support may be required.

Management of HG can be complicated because not all women respond to treatment. In some instances, women with HG may be able to avoid hospitalization by eating a special diet of clear liquids and bland food rich in carbohydrates, and eating before rising in the morning; while these may be of some assistance, they are unlikely to resolve the disorder on their own. Hypnosis has relieved symptoms in some cases. Wristbands used for motion sickness and seasickness have been shown by one study to be effective in treating some cases of HG; these are worn around the wrist at a traditional acupuncture point, 3 finger-widths from the joint, and are available at many pharmacies. There is evidence that ginger may be effective in treating pregnancy-related nausea; however, this is generally ineffective in cases of HG.

IV hydration
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. A and B vitamins are depleted within two weeks, so extended malnutrition indicates a need for evaluation and supplementation. Additionally, mineral levels should be monitored and supplemented; of particular concern are sodium and potassium.

After IV rehydration is completed, patients generally 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). Home treatment is often less expensive than long-term and/or repeated hospital stays.

Medications
While no medication is considered completely risk-free for use during pregnancy, there are several which are commonly used to treat HG and are believed to be safe.

The standard treatment in most of the world is Benedictin (also sold under the trademark name Diclectin), a combination of doxylamine succinate and vitamin B6. However, due to a series of birth-defect lawsuits in the United States against its maker, Merrill Dow, Benedictin is not currently on the market in the U.S. (None of the lawsuits were successful, and numerous independent studies and the Food and Drug Administration (FDA) have concluded that Benedictin does not cause birth defects.)  Its component ingredients are available over-the-counter (doxylamine succinate is the active ingredient in many sleep medications), and some doctors will recommend this treatment to their patients.

Antiemetic drugs, especially ondansetron (Zofran), are effective in many women. The major drawback of ondansetron has been its cost. In severe cases of HG, the Zofran pump may be more effective than tablets. Zofran is also available in ODT (oral disintegrating tablet) which can be easier for women who have trouble swallowing due to the nausea. Promethazine (Phenergan) has been shown to be safe, at least in rats and may be used during pregnancy with minimal/no side effects. Metoclopramide is sometimes used in conjunction with antiemetic drugs; however, it has a somewhat higher incidence of side effects. Other medications less commonly used to treat HG include Marinol, corticosteroids and antihistamines.

Other medications that are frequently prescribed for HG are Compazine, Tigan, Phenergan, and Reglan. These can be given orally, intraveneously, or as a rectal suppository. They are considered safe for use during pregnancy.

Anecdotal evidence suggests that the use of marijuana, or of the pharamaceutical extract Marinol can relieve the symptoms of HG, in a similar way to treating nausea in people with Cancer and AIDS. However, due to the criminalisation of cannabis, there have been no clinical trials into its effectivess or risks to the fetus. However, use of marijuana has been shown to increase the risk for central nervous system growth impairment, low birth weight infants, small for gestational age infants, and preterm deliveries, all of which are associated with poor infant outcomes.

Nutritional support
Women who do not respond 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 nasojejunum tube).

Support
It is important that women get early and aggressive care during pregnancy. This can help limit the complications of HG. Also, because depression can be a secondary condition of HG, emotional support, and sometimes even counseling, can be of benefit. It is important, however, that women not be stigmatized by the suggestion that the disease is being caused by psychological issues.