Ondansetron for Treatment of Nausea and Vomiting of Pregnancy and the Risk of Specific Birth Defects

OBJECTIVE: To use data from two large studies of birth defects to describe time trends in ondansetron use for the treatment of first-trimester nausea and vomiting of pregnancy and to investigate associations, either previously reported or undescribed, between first-trimester ondansetron use and major birth defects. METHODS: We used data from two case-control studies, the National Birth Defects Prevention Study (1997-2011) and the Slone Birth Defects Study (1997-2014). The prevalence of ondansetron use for the treatment of first-trimester nausea and vomiting of pregnancy among control patients was calculated in 2-year intervals. Using women with untreated first-trimester nausea and vomiting of pregnancy as the reference, we calculated adjusted odds ratios (ORs) and 95% CIs for associations between first-trimester ondansetron use for treatment of nausea and vomiting of pregnancy and specific birth defects. A secondary exposure group of other prescription antiemetics was used to address confounding by indication. RESULTS: In the National Birth Defects Prevention Study and Slone Birth Defects Study, respectively, 6,751 and 5,873 control mothers and 14,667 and 8,533 case mothers who reported first-trimester nausea and vomiting of pregnancy were included in the analysis. Among women in the control group, ondansetron exposure increased from less than 1% before 2000 to 13% in 2013-2014. Ondansetron use was not associated with an increased risk for most of the 51 defect groups analyzed. Modest increases in risk were observed for cleft palate (adjusted OR 1.6, 95% CI 1.1-2.3) in the National Birth Defects Prevention Study and renal agenesis-dysgenesis (adjusted OR 1.8, 95% CI 1.1-3.0) in the Birth Defects Study, although these findings may be the result of chance. CONCLUSION: Off-label use of ondansetron for the treatment of nausea and vomiting of pregnancy increased to 13% by the end of the study period. For the majority of specific birth defects investigated, there was no increased risk associated with first-trimester use of ondansetron for treatment of nausea and vomiting of pregnancy compared with no treatment, although modest associations with cleft palate and renal agenesis-dysgenesis warrant further study.