Clinical Review

Nausea and vomiting of pregnancy: Q&A with T. Murphy Goodwin

OBG Manag. 2004 August;16(8):54-67

References

1. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin: Nausea and Vomiting of Pregnancy. Clinical management guidelines for obstetrician-gynecologists. No. 52. Washington, DC: ACOG: April 2004.

2. Klebanoff M, Koslone P, Kaslow R, Rhoads G. Epidemiology of vomiting in early pregnancy. Obstet Gynecol. 1985;66:612-616.

3. Mazzotta P, Stewart D, Atanackovic G, Koren G, Magee LA. Psychosocial morbidity among women with nausea and vomiting of pregnancy: prevalence and association with antiemetic therapy. J Psychosom Obstet Gynaecol. 2000;21:129-136.

4. Mazzota P, Magee L, Koren G. Therapeutic abortions due to severe morning sickness. Unacceptable combination. Can Fam Physician. 1997;43:1055-1057.

5. Goodwin TM. Nausea and vomiting of pregnancy: an obstetric syndrome. Am J Obstet Gynecol. 2002;186:S184-S189.

6. Goodwin TM, Montoro M, Mestman JH, Pekary AE, Hershman JM. The role of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. J Clin Endocrinol Metab. 1992;75:1333-1337.

7. Goodwin TM, Hershman JM. Hyperthyroidism due to inappropriate production of human chorionic gonadotropin. Clin Obstet Gynecol. 1997;40:32-44.

8. Depue RH, Bernstein L, Ross RK, et al. Hyperemesis gravidarum in relation to estradiol levels, pregnancy outcome, and other maternal factors: a seroepidemiologic study. Am J Obstet Gynecol. 1987;156:1137-1141.

9. Vellacott ID, Cooke EJ, James CE. Nausea and vomiting in early pregnancy. Int J Gynaecol Obstet. 1988;27:57-62.

10. Gadsby R, Barnie-Adshead AM, Jagger C. A prospective study of nausea and vomiting during pregnancy. Br J Gen Prac. 1993;43:245-248.

11. Lacroix R, Eason E, Melzack R. Nausea and vomiting during pregnancy: a prospective study of its frequency, intensity, and patterns of change. Am J Obstet Gynecol. 2000;182:931-937.

12. Boles RG, Williams JC. Mitochondrial disease and cyclic vomiting syndrome. Dig Dis Sci. 1999;44:103S-107S.

13. Czeizel AE, Dudas I, Fritz G, Tecsoi A, Hanck A, Kunovits G. The effect of periconceptional multivitamin-mineral supplementation on vertigo, nausea and vomiting in the first trimester of pregnancy. Arch Gynecol Obstet. 1992;251:181-185.

14. Emelianova S, Mazzotta P, Einarson A, Koren G. Prevalence and severity of nausea and vomiting of pregnancy and effect of vitamin supplementation. Clin Invest Med. 1999;22(3):106-110.

15. Jednak MA, Shadigian EM, Kim MS, et al. Protein meals reduce nausea and gastric slow wave dysrhythmic activity in first trimester pregnancy. Am J Physiol. 1999;277:G855-G861.

16. Sahakian V, Rouse D, Sipes S, Rose N, Niebyl J. Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled study. Obstet Gynecol. 1991;78:33-36.

17. Vutyavanich T, Wongtrangan S, Ruangsri R. Pyridoxine for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol. 1995;173:881-884.

18. Koren G, Pastuszak A, Ito S. Drugs in pregnancy. N Engl J Med. 1998;338:1128-1137.

19. Park-Wyllie L, Mazzotta P, Pastuszak A, et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology. 2000;62:385-392.

20. Simpson SW, Goodwin TM, Robins SB, et al. Psychological factors and hyperemesis gravidarum. J Womens Health Gend Based Med. 2001;10:471-477.

21. Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol. 1998;41:597-605.

Effects on the mother and predisposing factors

Even at milder levels, physical discomfort is considerable. Predisposing factors include a female fetus, history of hyperemesis, migraine headaches, and a tendency to develop motion sickness.

OBG MANAGEMENT: How does NVP affect the mother?

GOODWIN: Serious sequelae are limited to hyperemesis, in which case Mallory-Weiss tears, splenic avulsion, esophageal rupture, pneumothorax, acute tubular necrosis, peripheral neuropathy (due to deficiencies of vitamins B6and B12), or Wernicke’s encephalopathy can result. This last condition is the most serious potential complication, and it can be difficult to recognize. Look for signs of confusion, memory loss, and blunted affect.

Even at milder levels of NVP, however, physical discomfort can be considerable. One prospective study using the McGill Nausea Questionnaire found the nausea experienced by pregnant women to be similar in character and intensity to that experienced by cancer patients on chemotherapy.¹¹

OBG MANAGEMENT: Are there predisposing factors?

GOODWIN: Yes. They include a history of illness upon exposure to estrogen (for example, oral contraceptives), as well as a history of motion sickness and migraine.

Hyperemesis is more likely when the fetus is female. Women who had hyperemesis in a previous pregnancy are likely to experience it again in their next gestation, and their daughters and sisters also are more likely to develop it.

Bendectin: The sad saga of a useful drug

The most widely prescribed drug for nausea and vomiting of pregnancy (NVP), Bendectin, was voluntarily withdrawn from the US market in 1982, after numerous, unsuccessful lawsuits alleged it had caused birth defects.

After its withdrawal, hospitalization rates for NVP doubled while solid evidence of Bendectin’s safety continued to accumulate. In the years since, researchers have found no difference in major malformations between infants in the general population and those born to women who took Bendectin. Nor has there been any decrease in specific malformations. As the New England Journal of Medicine pointed out, a decrease in the number of malformations “would be expected for a truly teratogenic drug estimated to have been used by up to 40% of pregnant women at one time.”¹⁸

The drug is still available in Canada, where it is marketed as Diclectin. In the US, its ingredients—pyridoxine (vitamin B6) and doxylamine—can be compounded by a pharmacy, or the patient can be instructed to take 10 to 25 mg of pyridoxine and 12.5 mg of Unisom (half a tablet) 3 or 4 times daily. (Unisom is an over-the-counter sleep aid containing doxylamine succinate.)

We also know that inherited and acquired disorders of mitochondria commonly manifest as migraine and/or gastrointestinal disease, including nausea and vomiting.¹²

Predisposing factors also include pregnancy-related conditions: multiple gestation; gestational trophoblastic disease; and fetal anomalies such as triploidy, Down’s syndrome, and hydrops fetalis. Overall, the chance of fetal defects associated with hyperemesis is extremely small.

The work-up: key signs and tests

In severe cases, look for Wernicke’s encephalopathy, dehydration, weight loss, other causes of nausea and vomiting, and abnormal lab values.

OBG MANAGEMENT: Let’s say you have a patient at 8 weeks’ gestation who complains of persistent nausea and vomiting. What is an appropriate work-up?

GOODWIN: Physical assessment is necessary only in severe cases. If nausea and vomiting last more than 3 weeks, signs of Wernicke’s encephalopathy should be sought (this condition is never reported as early as 8 weeks).

Other important signs to look for are dehydration and evidence of other diseases that can cause nausea and vomiting (TABLE). If the patient has experienced vomiting throughout her pregnancy, but it suddenly becomes acute, another condition may be responsible.

It also is important to be aware that abdominal pain, fever, and headache do not represent NVP, but usually reflect other conditions associated with nausea and vomiting.

I ask about the duration and severity of NVP, and whether the woman has lost weight as a result. Weight loss is very important: Women who can’t sustain their weight need nutritional therapy.

OBG MANAGEMENT: Do you order lab tests?

GOODWIN: Yes. In severe cases, I get a liver panel and check amylase, lipase, and electrolytes. A number of abnormalities have been documented when hyperemesis is present. They include elevated liver enzymes, serum bilirubin, and serum amylase or lipase measurements, as well as increased free thyroxine and suppressed thyroid-stimulating hormone.

Serum hCG measurements are generally not useful, however, in exploring whether the patient’s vomiting is caused by hyperemesis gravidarum.

Imaging is necessary only to check for predisposing causes such as twins or molar gestation.

TABLE

Differential diagnosis of nausea and vomiting of pregnancy