• Primary Outcomes:
  • Cardiac malformation: adjusted relative risk (RR) 0.99 (95% CI, 0.93–1.06)
  • Oral clefts: adjusted RR 1.24 (95% CI, 1.03–1.48)
• Secondary Outcome: Overall malformations: adjusted RR 1.01 (95% CI, 0.98–1.05)

Evidence-Based Medicine Commentary

1. Observational Study: The largest limitation to this study is the observational design. It demonstrates associations, not causation. Other confounders and co-variates could have been responsible for any difference discovered in the dataset with ondansetron exposure during pregnancy.
2. Exposed Women: The exposed pregnant women had different baseline characteristics than those women not exposed to ondansetron. Exposed pregnant women were more likely to smoke; have psychiatric diagnosis or neurologic condition; be white; and fill a prescription for other nausea and vomiting medication, psychotropics, steroids, and suspected teratogens. These differences could have affected the results.
3. External Validity: This dataset captured 1.5 million women and 1.8 million pregnancies. This is a large number but only represents 50 percent of all the pregnancies in the United States. The pregnant women included were Medicaid patients and may be different than pregnant women with other insurance types.

Bottom Line

Ondansetron exposure in early pregnancy does not appear to be associated with an overall increased risk of fetal malformations, but there may be a small statistical increased risk of oral clefts.

Case Resolution

You advise her that metoclopramide is recommended to be used before ondansetron. She responds well to a 5 mg oral dose in the emergency department. She is discharged home with a prescription for metoclopramide. You advise her to return if her nausea and vomiting do not improve, she is unable to tolerate oral intake, or she is losing weight.

Thank you to Dr. Nick Papalia who is currently completing his obstetrics and gynecology residency at the University of Calgary in Alberta, Canada.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine. 

References

1. ACOG Practice Bulletin No. 189 summary: nausea and vomiting of pregnancy. Obstet Gynecol. 2018;131(1):190-193.
2. Pasternak B, Svanström H, Hviid A. Ondansetron in pregnancy and risk of adverse fetal outcomes. N Engl J Med. 2013;368(9):814-823.