Ondansetron in Pregnancy and the Risk of Congenital Malformations: A Systematic Review.

OBJECTIVE: Ondansetron, not approved for use in pregnancy, is increasingly being prescribed for nausea and vomiting in pregnancy and hyperemesis gravidarum. A number of recent lawsuits have highlighted the possibility that ondansetron may cause congenital malformations. The aim of this study was to systematically review epidemiological evidence on the potential association of prenatal exposure to ondansetron and congenital malformations.

METHODS: Systematic searches in Medline and Embase were performed in June 2017 using controlled vocabulary and key words, and references of search results were reviewed. Full papers (RCTs, cohort, and case-control studies) were eligible for inclusion if they reported fetal outcomes of prenatal ondansetron exposure in humans. Excluded were: case reports, studies involving pre-medication with ondansetron prior to CS, animal studies, and foreign languages studies.

RESULTS: Ten epidemiologic studies were included: five large retrospective cohort studies, two prospective observational studies, two population-based case-controls. and a retrospective case series. Sample sizes ranged from 17 to 1 501 434 infants exposed to ondansetron. A case-control study identified an association between prenatal exposure to ondansetron and cleft palate, and one cohort study found an increased risk of cardiovascular defects. These findings were not reproduced in the other studies.

CONCLUSION: While further investigation of the literature is needed, our results highlight the paucity of evidence linking prenatal exposure to ondansetron to an increased risk of congenital malformations. There is a need for additional epidemiologic studies to confirm whether ondansetron represents a safe and effective alternative treatment for nausea and vomiting in pregnancy and hyperemesis gravidarum.