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Int J Epidemiol. 2019 Dec 20. pii: dyz255. doi: 10.1093/ije/dyz255. [Epub ahead of print]

Ondansetron use in the first trimester of pregnancy and the risk of neonatal ventricular septal defect.

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Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, PA, USA.
Department of Clinical Analytics, University of Pittsburgh Medical Centers, PA, USA.
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA, USA.
Department of Pharmaceutical Science, School of Pharmacy, University of Pittsburgh, PA, USA.
Department of Pathology, University of Pittsburgh, PA, USA.
Departments of Pediatrics and Epidemiology, Biostatistics and Occupational Health, McGill University, Quebec, Canada.



Literature is divided regarding the risk of neonatal ventricular septal defect (VSD) associated with first trimester ondansetron use in pregnancy.


We 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.


A 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.


First 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.


Pregnancy; first trimester; ondansetron; ventricular septal defect


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