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.

Interestingly, a number of “high-hCG” conditions are associated with increased NVP: molar pregnancy, multiple gestation, and Down’s syndrome. Conversely, trisomy 18 is a “low-hCG” condition anecdotally associated with reduced NVP.

OBG MANAGEMENT: What is estrogen’s role?

GOODWIN: Estradiol and hCG are the only 2 hormones ever found to differ when women with NVP are compared to controls. Women who get sick with estrogen exposure are much more likely to develop NVP. Some studies have found increased estradiol levels in women with NVP, compared with controls.^6,8 Conversely, low estradiol levels may reduce the risk of NVP. Take smoking, for example. It is associated with lower hCG and estradiol levels, and smokers are less likely than non-smokers to have NVP.

Studies also have focused on a possible link between cytokines and hyperemesis, and between hyperemesis and tumor necrosis factor alpha.

OBG MANAGEMENT: Do these findings alter clinical management?

GOODWIN: No. The findings about etiology do not affect management at present.

NVP can be protective or perilous

Some degree of nausea and vomiting affects the vast majority of pregnancies. Unless it is severe, however, NVP appears to have a protective effect on the fetus.

OBG MANAGEMENT: What is the prevalence of NVP, and what are its characteristics?

GOODWIN: About 70% to 85% of gravidas experience it.⁹ In the spectrum of NVP, about 50% of women experience both nausea and vomiting, 25% experience nausea alone, and 25% are unaffected.¹⁰

Hyperemesis gravidarum affects roughly 3 to 20 of every 1,000 pregnancies.

It generally is categorized according to the level of intervention required:

Mild NVP does not affect daily life.
Moderate NVP interferes with daily life.
Severe NVP, or hyperemesis, requires fluid and/or nutritional support. Hyperemesis is further defined as persistent vomiting, weight loss exceeding 5% of prepregnancy weight, and significant ketonuria, with or without electrolyte disturbances. Hospitalization usually is required.

OBG MANAGEMENT: What is the clinical course?

GOODWIN: NVP almost always appears before 10 weeks’ gestation. If it begins any later, it is likely the patient has a different condition associated with nausea and vomiting.

One study found that most women develop NVP at about 4 to 7 weeks’ gestation, and that it resolves at less than 10 weeks in about 30% of women, at 10 to 12 weeks in another 30%, and at 12 to 16 weeks in another 30%.¹⁰

As for diurnal changes, symptoms tend to occur with greater frequency early in the day.

OBG MANAGEMENT: Is NVP ever harmful for the fetus?

GOODWIN: It is associated with improved fetal outcomes unless hyperemesis supervenes. Then it is associated with mild fetal growth delays and rare cases of fetal death.

We lack studies of the long-term effects of severe NVP on the fetus, but starvation and weight loss in women during famine have been shown to cause many diverse problems in offspring later in adult life.

OBG MANAGEMENT: What do you make of evidence that suggests NVP plays a protective role in pregnancy?

GOODWIN: If true, it likely represents a vestigial response that is no longer beneficial—similar to thrombophilias in pregnancy, which played an important role protecting women against bleeding at childbirth but now are more of a clinical problem because of the associated thrombosis.

NVP at a glance: Pervasive, disabling, and undertreated

Prevalence. 70% to 85%.¹

Presentation. About 50% of women have both nausea and vomiting, 25% have nausea only, and 25% are not affected.¹⁰

Hyperemesis gravidarum. 3 to 20 of every 1,000 pregnancies. Marked by persistent vomiting, weight loss exceeding 5% of prepregnancy weight, and significant ketonuria.

Clinical course. If NVP is going to occur, it is present before 10 weeks’ gestation. It resolves at less than 10 weeks’ gestation in about 30% of women, at 10 to 12 weeks in another 30%, and at 12 to 16 weeks in another 30%.¹⁰

Predisposing factors. History of illness with estrogen exposure, motion sickness, migraine, or hyperemesis; mother or sister with hyperemesis; female fetus; mitochondrial disorders; multiple gestation; gestational trophoblastic disease; and fetal anomalies such as Down’s syndrome and triploidy.

Undertreatment. As many as 50% of women with severe NVP are not offered therapy.^3,4

Physical discomfort. Intensity and character similar to nausea and vomiting induced by cancer chemotherapy, even at milder levels of severity.¹¹

Social and psychological impact. Reduced job efficiency, lost work time, negative impact on family relationships and mental health, decision to terminate an otherwise desired pregnancy. Women with hyperemesis are more likely to have anxiety, depression, somatization, psychoticism, and obsessive-compulsive symptoms, but return to normal after delivery.²¹

Fetal effects. Improved fetal outcomes unless hyperemesis supervenes. Hyperemesis with maternal weight loss is associated with mild fetal growth delays and rare cases of fetal death.

Maternal effects. Not linked to adverse effects except for hyperemesis gravidarum, in which Wernicke’s encephalopathy, Mallory-Weiss tears, splenic avulsion, esophageal rupture, pneumothorax, acute tubular necrosis, or peripheral neuropathy (due to vitamins B6 and B12 deficiencies) can result.