Clinical Review

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

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

An expert tells why this common condition is undertreated, and what can help, including how to formulate the effective drug formerly marketed as Bendectin.

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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.

KEY POINTS

About 35% of gravidas have nausea and vomiting severe enough to disrupt their daily routine. As many as 50% of women with severe NVP are not offered antiemetic therapy, studies show.
At any level of severity, nausea and vomiting cause psychosocial morbidity.
Multivitamin use at the time of conception reduces the severity of nausea and vomiting.
When drug therapy is necessary, start with 10 to 25 mg pyridoxine (vitamin B₆) 3 or 4 times daily.
If nausea and vomiting continue, add 12.5 mg doxylamine (by halving the over-the-counter sleep aid Unisom) to each dose of pyridoxine. The pyridoxine-doxylamine combination is the same formulation as the highly effective drug Bendectin, which is no longer available in the US.

T. Murphy Goodwin, MD, a contributor to the new American College of Obstetricians and Gynecologists practice bulletin on nausea and vomiting of pregnancy (NVP),¹ tells why it is important to ask every patient about nausea and vomiting, when to intervene, and what the best treatments are—including a substitute compound for the no-longer-available drug Bendectin.

Dr. Goodwin is professor of obstetrics and gynecology at the Keck School of Medicine, University of Southern California, Los Angeles.

Many patients assume they must endure nausea, vomiting

Women do not always mention nausea and vomiting, believing they must “live with it.” Prompt intervention can stave off more severe NVP, so it makes sense for Ob/Gyns to raise the subject early.

OBG MANAGEMENT: What new information in the American College of Obstetricians and Gynecologists (ACOG) practice bulletin should the Ob/Gyn be aware of?

GOODWIN: Rather than “new information,” I would call it a change in emphasis. Previously, the focus was almost exclusively on life-threatening hyperemesis gravidarum, while lesser degrees of nausea and vomiting of pregnancy went untreated or undertreated. In reality, approximately 35% of gravidas have NVP severe enough to interfere with their daily routine. Fortunately, effective therapy is available.

OBG MANAGEMENT: Some authorities believe NVP is a continuum between mild upset and hyperemesis gravidarum. How would such a continuum affect patient care?

GOODWIN: Epidemiologic studies suggest that women with mild NVP and those with hyperemesis are significantly similar, strongly supporting the notion of a continuum.² This fact underscores the importance of treating NVP in its early stages, before it advances to hyperemesis.

My own sense is that a small group of women with hyperemesis are predisposed to it because of rare genetic disorders such as mitochondrial mutations.

OBG MANAGEMENT: Since so many women experience NVP, should obstetricians routinely ask about it, including its psychosocial effects?

GOODWIN: Yes. This is important because of the continuum we mentioned—and because many women consider NVP “normal” and may not mention it unless they are asked.

OBG MANAGEMENT: Do you think some physicians share this mindset?

GOODWIN: Undoubtedly. Studies have shown that as many as 50% of women with severe NVP are not offered antiemetic therapy.^3,4 But the days of letting the condition “run its course” are past. Now the best strategy is asking about it—and intervening early.

What causes NVP?

The factors at play in each patient help determine the best treatment. NVP is more likely with high levels of hCG and estrogen.

OBG MANAGEMENT: In a 2002 study,⁵ you concluded that NVP is actually a syndrome rather than a single condition.

How would this concept affect management of NVP?

GOODWIN: Women who are susceptible to NVP because of a vestibular mechanism might respond to a medical regimen that works at that site. Still other women may have “background” gastrointestinal motility dysfunction that makes them more susceptible to NVP; in that case, therapies to treat motility abnormalities would be appropriate. Others may have a strong behavioral overlay and would be expected to respond to the kinds of treatment used for anticipatory nausea and vomiting associated with chemotherapy.

These are theoretical scenarios at present, but a new paradigm will allow new ways of thinking about therapy.

OBG MANAGEMENT: In the early 1990s, you and your colleagues⁶ reported your study on the link between human chorionic gonadotropin (hCG) and NVP. What is the association?

GOODWIN: A temporal association has attracted the attention of obstetricians for years. In addition, biochemical hyperthyroidism and NVP are strongly associated. Fifty percent to 70% of women with hyperemesis gravidarum have transient hyperthyroidism, with no goiter.⁷ (If a goiter is present, suspect primary thyroid disorder.) Because hCG causes the biochemical hyperthyroidism related to pregnancy, and because hyperthyroidism by itself rarely causes vomiting, hCG is implicated. However, it remains unclear how hCG would cause NVP—perhaps by stimulating the ovary to produce more estrogen, which causes emesis, or through some other, unknown step.