Hyperemesis Gravidarum

Hyperemesis Gravidarum

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Hyperemesis Gravidarum is not the name you expected.

Disorder Subdivisions

  • None

General Discussion

Hyperemesis gravidarum (HG) is a rare disorder characterized by severe and persistent nausea and vomiting during pregnancy that may necessitate hospitalization. As a result of frequent nausea and vomiting, affected women experience dehydration, vitamin and mineral deficit, and the loss of greater than five percent of their original body weight.



Nausea and vomiting of pregnancy (NVP), more widely known as morning sickness, is a common condition of pregnancy. Many researchers believe that NVP should be regarded as a continuum of symptoms that may impact an affected woman's physical, mental and social well-being to varying degrees. Hyperemesis gravidarum represents the severe end of the continuum. No specific line exists that separates hyperemesis gravidarum from NVP; in most cases, affected individuals progress from mild or moderate nausea and vomiting to hyperemesis gravidarum. The exact cause of hyperemesis gravidarum is not known.

Symptoms

Hyperemesis gravidarum may develop rapidly within a few weeks or gradually over a few months. Individuals with hyperemesis gravidarum experience severe and persistent nausea and vomiting that occur before the 20th week of pregnancy (gestation) and are severe enough to result in progressive weight loss of greater than five percent of their original body weight. In addition, frequent vomiting may also lead to dehydration and vitamin and mineral deficit. Hyperemesis gravidarum often leads to hospitalization to restore lost fluids and nutrients to affected women.



Additional symptoms associated with hyperemesis gravidarum may include rising pulse rate, excessive salivation (ptyalism), and a rapid heartbeat (tachycardia). In some cases, affected individuals may have a distinct odor to their breath (ketonic odor). Symptoms associated with the disorder may subside and recur ("wax and wane") resulting in affected individuals being hospitalized more than once during their pregnancy.



Quality of life is also affected. Individuals are often unable to work, complete daily household tasks and routines, care for young children and, in some cases, may elect to skip social activities and functions. Persistent and severe nausea and vomiting associated with hyperemesis gravidarum may put a strain on various family relationships as well.



Outcome

A recent systematic review and meta-analysis of existing studies showed that infants of women who experienced hyperemesis gravidarum are significantly more likely to exhibit a lower birth weight, be small for gestational age, and to be born prematurely. In addition, some research has shown that low birth weight was more common in infants of women who were repeatedly hospitalized for hyperemesis gravidarum than infants of women who were hospitalized only once.



Only a few studies exist in the medical literature examining the long-term effects hyperemesis gravidarum may have on exposed offspring. One such study showed children whose mothers reported nausea in middle or late pregnancy had lower (task persistence) at age 5 (a marker of attention span) and were viewed by teachers as having more attention and learning problems at age 12. Additionally, another study showed approximately 9% of women with extreme weight loss in pregnancy (greater than 15% of pre-pregnancy weight) due to hyperemesis report having a child with a behavioral disorder. And a third study concluded adult offspring exposed to HG in utero were 3.6 times more likely to have a psychological and behavioral disorder with diagnoses primarily of depression, bipolar disorder and anxiety when compared to non-exposed offspring.

Causes

The exact cause of hyperemesis gravidarum is not known. Some theories concerning the cause of hyperemesis gravidarum include pregnancy hormone imbalances, vitamin B deficiency; hyperthyroidism; gastroesophageal reflux occurring in association with abnormalities in the electrical properties of muscles affecting the stomach (gastric dysrhythmias); Helicobacter Pylori infections; psychological factors; and disturbances in carbohydrate metabolism.



Many of these theories are based on symptoms coexisting with hyperemesis gravidarum that are just as likely to be caused by hyperemesis as they are to be causal. For example, many affected women are unable to tolerate vitamins and normal nutrition in pregnancy and therefore may develop vitamin deficiencies, thyroid, and other metabolic disturbances. Additionally, while in the first half of the 1900s theories for hyperemesis were dominated by far-fetched psychological proposals such as rejection of pregnancy due to embarrassment about sexual relations or fear of childbirth and motherhood, more recently, scientific studies have shown that 94% of women with hyperemesis have no prior psychiatric history and although women may be depressed or anxious during pregnancy when they are too nauseous to eat healthfully or care for their families, they revert back to normal when their extreme physical symptoms subside.



Finally, many women with no or normal nausea in pregnancy have H. Pylori infections and/or abnormally high levels of pregnancy hormones such as hCG and estrogen. Thus, despite several clinical studies, researchers have been unable to definitively determine why hyperemesis gravidarum occurs.



Several lines of evidence support a genetic predisposition to nausea and vomiting in pregnancy. In a study of nausea and vomiting of pregnancy in twins, concordance rates were more than twice as high for monozygotic compared to dizygotic twins. Studies suggest familial aggregation of hyperemesis gravidarum as there is a remarkably high prevalence of affected siblings and mothers of patients affected with nausea and vomiting of pregnancy and hyperemesis gravidarum, and a significantly increased risk to daughters and sisters of women with a history of HG. Additionally, a biologic component to the condition has been suggested from animal studies. There are also data suggestive of a role for genetic predisposition in the development of nausea and vomiting of pregnancy. However, the cause of hyperemesis gravidarum is currently unknown and the rationale for maintenance of genes that predispose to dehydration and malnutrition in pregnancy remains an evolutionary enigma. One would think that a condition that commonly resulted in maternal and fetal death before the introduction of intra venous fluids in the 1950s would have been strongly selected against in nature. Studies are currently being done to identify the cause of hyperemesis gravidarum and more information can be found at http://www.helpher.org/HER-Research/opportunities.php.

Some researchers have reported that certain factors may be associated with an increased risk of developing or increasing the duration of hyperemesis gravidarum including younger maternal age, high body weight (obesity), no previous completed pregnancies (nulliparity), carrying twins, a first-time pregnancy, a family history, allergies, restrictive diet, and/or a history of hyperemesis gravidarum in previous pregnancies.

Affected Populations

While nausea and vomiting of pregnancy in general is estimated to occur in 50 to 90 percent of all pregnancies, hyperemesis gravidarum is estimated to occur in .5 to two percent of pregnant women. Over 192,000 hospital visits and/or admissions occur in the US annually and approximately 4,000 Canadian women a year experience hyperemesis gravidarum, according to estimates from the U.S. Healthcare Cost and Utilization Project, and the Society of Obstetricians and Gynecologists of Canada. It is the second leading cause of hospitalization in early pregnancy and is more common in non-white and Asian populations.



Hyperemesis gravidarum, like nausea and vomiting of pregnancy, usually occurs before the 20th week of pregnancy often between the fourth and tenth week. In many cases, as with mild or moderate nausea and vomiting of pregnancy, symptoms resolve before 20 weeks. However, cases have been reported in which symptoms persisted after 20 weeks, and as many as 22 percent of cases may have symptoms that last until term. Hyperemesis gravidarum often occurs during first pregnancies and usually recurs in subsequent pregnancies.

Standard Therapies

The diagnosis of hyperemesis gravidarum may be confirmed by a thorough clinical evaluation, detailed patient history, and the identification of characteristic symptoms (e.g., persistent and severe nausea and vomiting, dehydration, and weight loss). The diagnosis is one of exclusion as other causes of nausea and vomiting during pregnancy must be ruled out. Physicians should determine the frequency of nausea and vomiting and the extent to which they affect an affected individual's daily life.



Treatment

The diagnosis of hyperemesis gravidarum should lead to immediate hospitalization of an affected individual in order to restore fluids and replace electrolytes by infusing medication and fluids through veins (intravenously). Food should not be given through the mouth (orally) until vomiting stops and dehydration has been corrected. Instead, food may be supplied by way of the intestines (enteral feeding) or by injection through some other route (parenteral feeding).



Vitamin supplementation (particularly vitamins B6, C and thiamine) may also be recommended. Thiamine supplementation is specifically recommended to prevent the development of Wernicke's encephalopathy.



With these treatments, in many cases, vomiting may stop. If vomiting continues, antiemetic drug therapy may be recommended. (For more information on antiemetic drugs, see the Investigational Therapies section of this report.)



After vomiting stops, affected individuals should receive enteral nutritional supplementation as needed to calm nausea. Physicians should then slowly and carefully reintroduce fluids and small, frequent meals into an affected individual's diet. Meals should consist of foods that are high in carbohydrates and low in fat.



In some cases, counseling may be recommended for women to help deal with the complications of hyperemesis gravidarum. In addition, treatments for mild or moderate nausea and vomiting in pregnancy may also be of benefit. These common treatments include plenty of bed rest, avoiding odors that may trigger an episode of nausea or vomiting, and dietary changes (i.e., avoiding foods that worsen nausea and vomiting). However, no clinical data exist to prove the effectiveness of these treatments.

Investigational Therapies

In some persistent cases of hyperemesis gravidarum, drugs that prevent or lessen nausea and vomiting may be prescribed (antiemetic drug therapy). In Canada, the drug diclectin, which contains an antihistamine (doxylamine succinate) and vitamin B6 (pyridoxine), is approved for treatment of nausea and vomiting of pregnancy. Diclectin is the only drug in Canada labeled as safe and effective to treat nausea and vomiting of pregnancy. It is not currently available in the United States, but papers presented at a May 2002 conference on Understanding and Treating Nausea and Vomiting of Pregnancy, sponsored by the National Institute of Child Health and Human Development and The Office of Rare Diseases, National Institutes of Health, proposed that it's possible use in the U.S. be studied.



The ingredients of diclectin are the same as those of bendectin, a drug used to treat nausea and vomiting in pregnancy in the United States from 1956 to 1983. After numerous lawsuits were filed claiming bendectin caused various birth defects, the drug's manufacturer voluntarily withdrew it from the market, citing rising legal costs and negative publicity. However, despite bendectin's becoming the most studied drug in regard to pregnancy, no research has ever demonstrated an increased incidence of birth defects in association with the use of bendectin. In fact, the Food and Drug Administration (FDA) has determined that bendectin was not withdrawn from the market for reasons of safety or effectiveness.



Other antihistamines have been used to treat nausea and vomiting in pregnancy, sometimes in conjunction with diclectin. These include dimenhydrinate (Gravol), hydroxyzine (Atarax), and promethazine (Phenergan). Most medications are not very effective in treating severe hyperemesis, leading to a high rate of therapeutic termination. In the U.S., serotonin inhibitors such as Ondansetron (Zofran), intravenous fluids, and steroids are reported by patients to be the most effective in treating nausea and vomiting, but none are cures. Importantly, these drugs have not been studied thoroughly in pregnant women, and their FDA approval labeling cautions that they are not approved for pregnant or nursing women. While these drugs have been studied in pregnant women and have not been shown to increase the risk of congenital anomalies (with the exception of first trimester exposure to steroids), the long-term effect on the mother and exposed child are currently unknown. However, the long-term effects of nutritional disturbances caused by untreated hyperemesis are equally understudied. Meanwhile the link between poor diet in otherwise normal pregnancies and cross-generational effects are well known and are likely to be mimicked in some cases of hyperemesis gravidarum.



Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com



For more information on the Genetics and Epidemiology of Hyperemesis Gravidarum Study, please contact Dr. Marlena Fejzo at nvpstudy@usc.edu or read more at http://www.helpher.org/HER-Research/opportunities.php.

References

Yamada T, et al., eds. Textbook of Gastroenterology, 2nd Ed.; J.B. Lippincott Company; Philadelphia, PA; 1995:1026-27.



Bennett JC, Plum F., eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:630, 787, 787t.



Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:2056-57.



Berkow R., ed. The Merck Manual-Home Edition. Whitehouse Station, NJ: Merck Research Laboratories; 1997:1158.



REVIEW ARTICLES

Supplement to The Journal of the American College of Obstetrics and Gynecology. Understanding and Treating Nausea and Vomiting of Pregnancy. May 2002. 186(5). Proceedings of a November 2000 conference organized by: T. Murphy Goodwin, MD of the University of Southern California, Jennifer Niebyl, MD of the University of Iowa, Charlotte Catz, MD, Chief, Pregnancy and Perinatology Branch, NICHHD, and Roberto Romero, MD, Chief, Perinatal Research Branch, NICHHD.



Kuscu NK, Koyuncu F. Hyperemesis gravidarum: current concepts and management. Postgrad Med J. 2001;78:76-79.



Williamson C. Drugs in pregnancy. Gastrointestinal disease. Best Pract Res Clin Obstet Gynaecol. 2001;15:937-52.



Eliakim R, Abulafia O, Sherer DM. Hyperemesis gravidarum: a current review. Am J Perinatol. 2000;17:207-18.



Caffrey TJ. Transient hyperthyroidism of hyperemesis gravidarum: a sheep in wolf's clothing. J AM Board Fam Pract. 2000;13:35-38.



JOURNAL ARTICLES

Fejzo MS, Poursharif B, Korst L, Munch S, MacGibbon KW, Romero R, Goodwin TM Symptoms and pregnancy outcomes associated with extreme weight loss among women with hyperemesis gravidarum, J of Womens Health, in press.



Mullin PM, Ching C, Schoenberg F, MacGibbon K, Romero R, Goodwin TM, Fejzo MS: Risk factors, treatments, and outcomes associated with prolonged hyperemesis gravidarum. J Matern Fetal Neonatal Med Epub Sep 15, 2011.



Mullin P, Bray A, Schoenberg-Paik F, MacGibbon K, Romero R, Goodwin TM, Fejzo MS: Prenatal Exposure to Hyperemesis Gravidarum Linked to Increased Risk of Psychological and Behavioral Disorders in Adulthood. J Dev Origins of Disease. 2011; 2:200-204.

Veenendaal MV, van Abeelen AF, et al. Consequences of hyperemesis gravidarum for offspring: a systematic review and meta-analysis. BJOG 2011;118(11):1302-1313.



Zhang Y., Cantor R., MacGibbon K, Romero R, Goodwin TM, Mullin P, Schoenberg Fejzo M. Familil Aggregation of Hyperemesis Gravidarum. AJOG 2011 Mar;204(3):230.e1-7.





Vikanes A, Skjaerven R, Grjibovski AM, Gunnes N, Vangen S, Magnus P. Recurrence of hyperemesis gravidarum across generations: population based cohort study. BMJ. 2010 Apr 29;340:c2050.



Fejzo MS, Ingles SA, Wilson M, Wang W, Mac Gibbon K, Romero R, et al.. High prevalence of severe nausea and vomiting of pregnancy and hyperemesis gravidarum among relatives of affected individuals. Eu J Obstet Gynecol 2008; 141:13-17.



Goodwin TM, Poursharif B, Korst LM, MacGibbon K, Fejzo MS: Secular trends in the treatment of hyperemesis gravidarum. Am J Perinatol, 25(3):141-7 (2008).



Poursharif B, Korst L, MacGibbon KW, Fejzo MS, Romero R, Goodwin TM. Elective pregnancy termination in a large cohort of women with hyperemesis gravidarum. Contraception, 76(6):451-5 (2007).



Seng JS, Schrot JA, van De Ven C, Liberzon I. Service use data analysis of pre-pregnancy psychiatric and somatic diagnoses in women with hyperemesis gravidarum. J Psychosom Obstet Gynaecol. 2007 Dec;28(4):209-17.



Gazmararian JA, Petersen R, Jamieson DJ, Schild L, Adams MM, Deshpande AD, Franks AL. Hospitalizations during pregnancy among managed care enrollees. Obstet Gynecol 2002;100:94-100.



Munch S. Women's experiences with a pregnancy complication: causal explanations of hyperemesis gravidarum. Soc Work Health Care. 2002;36(1):59-76.



Togay-Isikay C, Yigit A, Mutluer N. Wernike's enxcephalopathy due to hyperemesis gravidarum: an underecognized condition. Aust NZ J Obstet Gynaecol Suppl. 2001;41:453-56.



Werntoft E, Dykes AK. Effect of acupressure on nausea and vomiting during pregnancy. A randomized, placebo-controlled pilot study. J Reproduct Med. 2001;46:835-39.



Simpson SW, Goodwin TM, Robins SB, et al. Psychological factors and hyperemesis gravidarum. J Women's Health Gend Based Med. 2001;10:471-77.



Duggar CR, Carlan SJ. The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: a randomized, double-blind controlled study. Obstet Gynecol. 2001;97(4 Suppl 1):S45.



Power ML, Holzman GB, Schulkin J. A survey on the management of nausea and vomiting in pregnancy by obstetricians/gynecologists. Prim Care Update Ob Gyns. 2001;8:69-72.



Buttino L Jr, Coleman SK, Bergauer NK, et al. Home subcutaneous metoclopramide therapy for hyperemesis gravidarum. J Perinatol. 2000;20:359-62.



Russo-Steiglitz KE, Levine AB, Wagner BA, et al. Pregnancy outcome in patients requiring parenteral nutrition. J Matern Fetal Med. 1999;8:164-67.



Martin RP, Wisenbaker J, Huttunen MO. Nausea during pregnancy: relation to early childhood temperament and behavior problems at twelve years. J Abnorm Child Psychol 1999;27(4):323-9.



Corey LA, Berg K, Solaas MH, Nance WE. The epidemiology of pregnancy complications and outcome in a Norwegian twin population. Obstetrics and Gynecology 1992; 80:989-994.



Czaja JA. Food rejection by female rhesus monkeys during the menstrual cycle and early pregnancy. Physiology and Behavior 1975; 14:579-87.

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