The Case

A 28-year-old woman presents with nausea and vomiting during pregnancy. She is at eight weeks’ gestation and frustrated that nothing has worked. She has tried ginger, acupressure, vitamin B6 with doxylamine, and dimenhydrinate. A friend in her prenatal class told her about ondansetron, but a quick Google search mentioned birth defects, and this scared her. She wants to know what else she could safely try.

Background

Nausea and vomiting in pregnancy is a very common and frustrating condition. In more than 30 percent of women, the symptoms can become clinically significant. The most common cause of hospitalization in early pregnancy is hyperemesis gravidarum.

The American College of Obstetricians and Gynecologists has published an algorithm for nausea and vomiting in pregnancy in a practice guideline (see Figure 1).¹ It starts with nonpharmacological options like acupressure with wrist bands (despite evidence of efficacy). Pharmacological options include vitamin B6 alone or in combination with doxylamine. The next step is adding dimenhydrinate, prochlorperazine, or promethazine. The algorithm then dichotomizes into no dehydration or dehydration with persistent symptoms. It is at this step when ondansetron is added as a possible treatment.

The evidence of fetal safety of ondansetron is conflicting. An observational study showed that ondansetron taken during pregnancy was not associated with an important increased risk of fetal harm.²

(click for larger image) Figure 1: Algorithm for Nausea and Vomiting of Pregnancy
Source: Obstet Gynecol. 2018;131(1):190-193. Reprinted with permission.

Clinical Question

Is the use of ondansetron during pregnancy associated with congenital malformations?

The Study

Huybrechts KF, Hernández-Díaz S, Straub L, et al. Association of maternal first-trimester ondansetron use with cardiac malformations and oral clefts in offspring. JAMA. 2018;320(23):2429-2437.

• Population: Women ages 12 to 55 years on Medicaid from three months prior to conception to one month postpartum.
• Exposure: Women who were pregnant and filled at least one prescription for ondansetron during the first three months (12 weeks) of pregnancy.
  • Excluded: Women who filled a prescription during the three months before the start of their pregnancy.
• Comparison: Woman who were pregnant and filled a prescription for pyridoxine, promethazine, metoclopramide, or any alternative treatments.
• Outcome:
  • Primary Outcomes: Cardiac malformations and oral clefts diagnosed within 90 days after delivery.
  • Secondary Outcomes: Subgroups of cardiac malformations and oral clefts evaluated along with congenital malformations overall.

Authors’ Conclusions

“Among offspring of mothers enrolled in Medicaid, first-trimester exposure to ondansetron was not associated with cardiac malformations or congenital malformations overall after accounting for measured confounders but was associated with a small increased risk of oral clefts.”

Key Results: This observational study included 1.5 million women and 1.8 million pregnancies. The mean age was 24 years, and 5 percent were potentially exposed to ondansetron in the first trimester.

No increased risk of cardiac malformation was observed, but there was a statistical increase in the risk of oral clefts.