• Lara S Lemon, Lisa M Bodnar, William Garrard, Raman Venkataramanan, Robert W Platt, Oscar C Marroquin, and Steve N Caritis.
• Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, PA, USA.
• Int J Epidemiol. 2020 Apr 1; 49 (2): 648-656.

BackgroundLiterature is divided regarding the risk of neonatal ventricular septal defect (VSD) associated with first trimester ondansetron use in pregnancy.MethodsWe evaluated the risk of VSD associated with first trimester exposure to intravenous or oral ondansetron in 33 677 deliveries at Magee-Womens Hospital in Pittsburgh, PA (2006-2014). Using log-binomial regression, we evaluated the risk: (1) in the full cohort, (2) using propensity score designs with both matching and inverse probability weighting and (3) utilizing clustered trajectory analysis evaluating the role of dose. Sensitivity analyses assessed the association between ondansetron and all recorded birth defects in aggregate.ResultsA total of 3733 (11%) pregnancies were exposed to ondansetron in the first trimester (dose range: 2.4-1008 mg). Ondansetron was associated with increased risk of VSD with risk ratios ranging from 1.7 [95% confidence interval (CI) 1.0-2.9] to 2.1 (95% CI 1.1-4.0) across methods. Risks correspond to one additional VSD for approximately every 330 pregnancies exposed in the first trimester. The association was dose-dependent with increased risk in women receiving highest cumulative doses compared with lowest doses [adjusted risk ratio: 3.2 (95% CI 1.0-9.9)]. The association between ondansetron and congenital malformations was diluted as the outcome included additional birth defects.ConclusionsFirst trimester ondansetron use is associated with an increased risk of neonatal VSD potentially driven by higher doses. This risk should be viewed in the context of risks attributable to severe untreated nausea and vomiting of pregnancy.© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

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