Hyperemesis gravidarum

Hyperemesis gravidarum, with metabolic derangement
Classification and external resources
ICD-10 O21.1
ICD-9 643.1

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%.[2]

Contents

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)[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 afterward. It is thought that estrogen produces nausea and regurgitation of stomach acids in some women. [4] There is also evidence that leptin may play a role in HG.[5]

A recent study gives "preliminary evidence" that there may be a genetic component.[6]

Symptoms of morning sickness, and HG, can be aggravated by the following factors: hunger, fatigue, prenatal vitamins (especially those containing iron), odors, and diet.[7]

Symptoms

When HG is severe and/or inadequately treated, it may result in:

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.

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. On rare occasions a woman can die from hyperemesis; Charlotte Bronté is a presumed victim of the disease.[8]

For the fetus

Infants of women with severe hyperemesis that 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 that have a pregnancy weight gain of more than 7 kg appear similar as infants from uncomplicated pregnancies.[9] No long-term follow-up studies have been conducted on children of hyperemetic women.

Diagnosis

Women experiencing hyperemesis gravidarum often are dehydrated and lose 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.[10]

Fever, abdominal pain, or late onset of nausea and vomiting usually indicate another condition, such as appendicitis, gallbladder disorders, gastritis, hepatitis, or infection.[10]

Treatment

Because of the potential for severe dehydration and other complications, HG is in general 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,[11] 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, though the majority of women do not respond to this measure.[12] Wristbands used for motion sickness and seasickness have been shown by one study to be effective in treating some cases of HG, but not others; these are worn around the wrist at a traditional acupuncture point, 3 finger-widths from the joint, and are available at many pharmacies.[13] There is evidence that ginger may be effective in treating pregnancy-related nausea; however, in general this is 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.[14] A and B vitamins are depleted within two weeks, so extended malnutrition indicates a need for evaluation and supplementation. In addition, mineral 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). 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 that 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 or intraveneously, or administered as a rectal suppository. They are considered safe for use during pregnancy.[15]

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.[16] However, use of marijuana has been shown to increase the risk for central nervous system growth impairment, low birth weight and size of infants, and preterm deliveries, all of which are associated with poor infant outcomes. [17] [18]

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 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.

References

  1. ^ Hyperemesis Education & Research Foundation Understanding Hyperemesis: Overview
  2. ^ Eliakim, R., Abulafia, O., & Sherer, D. M. (2000). "Hyperemesis gravidarum: A current review". American Journal of Perinatology 17 (4): 207–218. doi:10.1055/s-2000-9424. PMID 11041443. 
  3. ^ Hershman JM (June 2004). "Physiological and pathological aspects of the effect of human chorionic gonadotropin on the thyroid". Best Pract. Res. Clin. Endocrinol. Metab. 18 (2): 249–65. doi:10.1016/j.beem.2004.03.010. PMID 15157839. http://linkinghub.elsevier.com/retrieve/pii/S1521690X0400020X. 
  4. ^ Carlson, Karen J., MD; Eisenstat, Stephanie J., MD; Ziporyn, Terra, PhD (2004). The New Harvard Guide to Women's Health. Harvard University Press. pp. 392–3. ISBN 0674013433. 
  5. ^ Aka N, Atalay S, Sayharman S, Kiliç D, Köse G, Küçüközkan T (2006). "Leptin and leptin receptor levels in pregnant women with hyperemesis gravidarum". The Australian & New Zealand journal of obstetrics & gynaecology 46 (4): 274–7. doi:10.1111/j.1479-828X.2006.00590.x. PMID 16866785. 
  6. ^ Fejzo MS, Ingles SA, Wilson M, et al. (August 2008). "High prevalence of severe nausea and vomiting of pregnancy and hyperemesis gravidarum among relatives of affected individuals". European journal of obstetrics, gynecology, and reproductive biology 141 (1): 13. doi:10.1016/j.ejogrb.2008.07.003. PMC 2660884. PMID 18752885. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2660884. 
  7. ^ Carlson, Karen J., MD; Eisenstat, Stephanie J., MD; Ziporyn, Terra, PhD (2004). The New Harvard Guide to Women's Health. Harvard University Press. pp. 392–3. ISBN 0674013433. 
  8. ^ Medscape
  9. ^ Dodds L, Fell DB, Joseph KS, Allen VM, Butler B. (2006). "Outcomes of pregnancies complicated by hyperemesis gravidarum.". Obstet Gynecol. 2006 Feb;107(2 Pt 1):285-92. 107 (2 Pt 1): 285–92. doi:10.1097/01.AOG.0000195060.22832.cd. PMID 16449113. 
  10. ^ a b "eMedicine - Pregnancy, Hyperemesis Gravidarum - Diagnosis and Differentials : Article by Susan Renee Wilcox, MD". Archived from the original on 2008-02-08. http://web.archive.org/web/20080208085520/http://www.emedicine.com/EMERG/topic479_2.htm. Retrieved 2008-02-02. 
  11. ^ Carlson, Karen J., MD; Eisenstat, Stephanie J., MD; Ziporyn, Terra, PhD (2004). The New Harvard Guide to Women's Health. Harvard University Press. pp. 392–3. ISBN 0674013433. 
  12. ^ Carlson, Karen J., MD; Eisenstat, Stephanie J., MD; Ziporyn, Terra, PhD (2004). The New Harvard Guide to Women's Health. Harvard University Press. pp. 392–3. ISBN 0674013433. 
  13. ^ Carlson, Karen J., MD; Eisenstat, Stephanie J., MD; Ziporyn, Terra, PhD (2004). The New Harvard Guide to Women's Health. Harvard University Press. pp. 392–3. ISBN 0674013433. 
  14. ^ British National Formulary (March 2003). "4.6 Drugs used in nausea and vertigo - Vomiting of pregnancy". BNF (45 ed.). 
  15. ^ Carlson, Karen J., MD; Eisenstat, Stephanie J., MD; Ziporyn, Terra, PhD (2004). The New Harvard Guide to Women's Health. Harvard University Press. pp. 393. ISBN 0674013433. 
  16. ^ http://www.cannabis-med.org/data/pdf/2002-03-04-4.pdf
  17. ^ http://ajph.aphapublications.org/cgi/content/abstract/73/10/1161
  18. ^ http://aje.oxfordjournals.org/content/124/6/986.short