Background: Ondansetron is commonly used to treat nausea and vomiting in pregnancy despite inconclusive evidence of its safety. Previous studies have reported no increase in risk of miscarriage but relied on methods that failed to account for gestational weeks at risk and non-user comparators, which may increase the potential for unmeasured confounding. Our objective was to estimate the risk of miscarriage among women prescribed ondansetron vs alternative antiemetics during the first 20 weeks of pregnancy.
Methods: A pregnancy cohort was created using electronic health record data from a health care system in North Carolina. Women were classified as exposed to either ondansetron or comparator antiemetics (metoclopramide or promethazine) based on the first antiemetic prescription received in the first 20 weeks of gestation. Cumulative incidence of miscarriage at 20 weeks was estimated in each antiemetic group. Hazard ratios (HR) were estimated with 95% confidence intervals and measured confounding was controlled using inverse probability of treatment weights. Sensitivity analyses assessed the potential impact of exposure misclassification, latency period, and selection bias.
Results: We identified 2620 eligible pregnancies with antiemetic orders; 65% had a first ondansetron order and 35% had a first comparator antiemetic order. In total, 95 women had a miscarriage. After adjustment, there was no difference in risk of miscarriage (HR 1.21, 95% CI 0.77, 1.90). Results from the per-protocol and other sensitivity analyses were similar to the main analysis.
Conclusions: We did not observe an increase in the risk of miscarriage for pregnancies exposed to ondansetron vs comparator antiemetics.
Keywords: electronic health records; miscarriage; nausea and vomiting; ondansetron; pharmacoepidemiology; pregnancy.
© 2020 John Wiley & Sons Ltd.