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."[1] 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."

Cause
The cause of HG is unknown. The leading theories speculate 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)[3] 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.

Additional theories point to high levels of estrogen and progesterone[citation needed], which may also be to blame for hypersalivation; decreased gastric motility (slowed emptying of the stomach and intestines); immune response to fragments of chorionic villi that enter the maternal bloodstream; or immune response to the "foreign" fetus.[citation needed]

There is also evidence that leptin may play a role in HG.

Historically, HG was blamed upon a psychological condition of the pregnant women. Medical professionals believed it was a reaction to an unwanted pregnancy or some other emotional or psychological problem.[citation needed] This theory has been disproved, but unfortunately some medical professionals espouse this view and fail to give patients the care they need.[citation needed]

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

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 20% 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.

Complications
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.

For the fetus
No long-term follow-up studies have been conducted on children of hyperemetic women. Children born to hyperemetic women appear to have no greater risk of complications or birth defects than the general population. However, recent research in fetal programming indicates that prolonged stress, dehydration and malnutrition during pregnancy can put the fetus at risk for chronic disease, such as diabetes or heart disease, later in life, or neurobehaviorial issues from birth. This underscores the importance of aggressive treatment of the condition.

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 and the vomiting is involuntary.

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. Coping strategies for uncomplicated morning sickness, which may include eating a bland diet and eating before rising in the morning, may be of some assistance but are unlikely to resolve the disorder on their own. 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.

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.