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.
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.
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.
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.
Treatment of first-trimester nausea and vomiting of pregnancy with ondansetron is not associated with an increased risk of most birth defects investigated.
Boston University School of Public Health, Slone Epidemiology Center at Boston University, and Massachusetts Center for Birth Defects Research and Prevention, Boston, Massachusetts.
Corresponding author: Samantha E. Parker, PhD, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118; email: firstname.lastname@example.org.
Supported in part by cooperative agreements U01DD000493 and U01DD001037 between the Birth Defects Branch of the Centers for Disease Control and Prevention and the Massachusetts Department of Public Health. Samantha E. Parker was supported by K01HL133600 from the National Institutes of Health. Coding of drug information in the National Birth Defects Prevention Study used the Slone Drug Dictionary under license from the Slone Epidemiology Center of Boston University.
Financial Disclosure Dr. Mitchell serves on the Tecfidera Pregnancy Registry Advisory Committee supported by Biogen. The other authors did not report any potential conflicts of interest.
Presented at the 48th Annual Meeting of the Society for Epidemiologic Research, June 16–19, 2015, Denver, Colorado; the 31st Annual International Conference on Pharmacoepidemiology and Therapeutic Risk Management, International Society for Pharmacoepidemiology, August 22–26, 2015, Boston, Massachusetts; and the 18th Annual Meeting of the National Birth Defects Prevention Network, October 19–20, 2015, Arlington, Virginia.
For a list of acknowledgments related to this study, see Appendix 1 online at http://links.lww.com/AOG/B102.
Each author has indicated that he or she has met the journal's requirements for authorship.
Received January 9, 2017. Received in revised form March 21, 2018. Accepted March 29, 2018.