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.

Adding other drugs

When pyridoxine is insufficient (alone or in combination with doxylamine), add promethazine, dimenhydrinate, or another agent.

OBG MANAGEMENT: How safe are antiemetics in pregnancy?

GOODWIN: The safety of antihistamines for use in pregnancy is well established. There are fewer data for phenothiazines, but they also appear to be quite safe.

As for 5-HT3-receptor antagonists, no teratogenicity has been found for ondansetron, which is used to treat nausea and vomiting associated with chemotherapy. However, in the only randomized trial, it did not appear to offer benefit over promethazine (a drug with characteristics of both antihistamines and phenothiazines and a good safety profile). Another drug, granisetron, has not been studied in regard to NVP.

OBG MANAGEMENT: What drugs do you prescribe besides pyridoxine and doxylamine?

GOODWIN: If the combination of pyridoxine and doxylamine fails to provide relief, I add 12.5 to 25 mg of promethazine every 4 hours (orally or rectally) or 50 to 100 mg of dimenhydrinate every 4 to 6 hours (orally or rectally, but not exceeding 200 mg daily when the patient is also taking doxylamine).

If this regimen fails to ease the patient’s symptoms, other combinations can be suggested.

OBG MANAGEMENT: Any caveats?

GOODWIN: I never give droperidol, a butyrophenone, because the US Food and Drug Administration has warned of an association with cardiac arrhythmias. This linkage may be overstated, but since there are safe alternatives, I avoid this agent.

Last resort: corticosteroids

Corticosteroids may help resolve refractory hyperemesis gravidarum.

OBG MANAGEMENT: What about corticosteroids? What is their safety profile for NVP?

GOODWIN: They do not appear to be teratogenic unless they are given during the first 10 weeks of gestation; then they are associated with a slightly increased risk of oral clefts.¹⁹ Even so, they should be a last resort—and then only in refractory cases involving weight loss and the need for enteral or parenteral nutrition. The literature is mixed on the efficacy, but I find that a subset of patients have a dramatic response to corticosteroids.

The usual regimen is 16 mg methylprednisolone 3 times daily for 3 days, followed by tapering over 2 weeks, declining in 4-mg increments. If vomiting occurs during the taper, increase the dose by 4 mg for 1 week, then continue tapering. If vomiting recurs after tapering, restart the drug at 8 to 12 mg/day. All told, therapy should be limited to 4 to 6 weeks.

If there is no improvement during the initial 3 days of therapy, stop the drug altogether.

The steroid can be given orally or intravenously. It also is important to give 1,200 mg daily of calcium throughout the regimen.

Hydration and nutrition for hyperemesis

Give fluids and nutritional support to maintain weight.

OBG MANAGEMENT: Do you hydrate the patient? What about enteral or parenteral nutrition?

The most extreme psychosocial effect of NVP is the decision to terminate an otherwise desired pregnancy.

GOODWIN: Yes. If she is dehydrated, I replace fluids, taking care to give intravenous thiamine before dextrose if she has been vomiting longer than 3 weeks. Otherwise, Wernicke’s encephalopathy may develop.

I prefer enteral nutrition, provided the patient can tolerate it and a good nutrition team is available to support both physician and patient.

Generally, hospitalization is warranted for women who cannot maintain hydration or nutrition or when the patient and her family cannot cope with the condition. However, depending on community resources, outpatient hydration/nutrition may be a feasible option.

When she is able to tolerate oral hydration and maintain weight—with or without nutritional support—she can be discharged.

Crippling psychosocial effects

Acknowledging NVP’s disruptive effect—at all levels of severity—is critical. Let her know you aren’t minimizing its impact, and that a range of options are at her disposal.

OBG MANAGEMENT: One aspect of NVP often overlooked is the psychosocial impact. Would you say it is considerable?

GOODWIN: Yes. In some cases, it can be crippling. Unfortunately, this dimension is rarely addressed by the physician. Effects can include reduced job efficiency, lost work time (in 1 study, a mean of 62 hours¹⁰), and a negative impact on family relationships and mental health. The most extreme effect, of course, is the decision to terminate an otherwise desired pregnancy.

These effects are not limited to hyperemesis; NVP involves psychosocial morbidity at all levels of severity.³ One study concluded that the severity of NVP fails to adequately reflect the distress it causes.³

The patient’s sense of her condition is critical. It is important to find out what effects NVP is having on her daily routine and let her know you aren’t minimizing its impact—also that a range of options are at her disposal.