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

      Abstract

      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.

      Résumé

      Objectif

      L'ondansétron n'a pas été approuvé chez les femmes enceintes; or il est de plus en plus prescrit pour traiter la nausée, les vomissements et l'hyperémèse associés à la grossesse. Un certain nombre de poursuites en justice a souligné récemment la possibilité que ce médicament soit à l'origine de malformations congénitales. Cette étude visait à faire un examen systématique des données épidémiologiques sur l'association potentielle entre l'exposition prénatale à l'ondansétron et les malformations congénitales.

      Méthodologie

      En juin 2017, nous avons mené des recherches systématiques dans Medline et Embase à l'aide d'une terminologie et de mots-clés contrôlés, et avons examiné les références des résultats obtenus. Les articles en texte intégral (ECR, études de cohorte, études cas-témoin) étaient admissibles s'ils faisaient état des résultats de l'exposition prénatale à l'ondansétron chez l'humain. Les déclarations de cas, les études portant l'administration du médicament en vue d'une césarienne, les études sur des animaux et les études de langue étrangère ont été exclues.

      Résultats

      Dix études épidémiologiques ont été retenues : cinq grandes études de cohorte rétrospectives, deux études observationnelles prospectives, deux études cas-témoin basées sur des populations et une étude de série de cas rétrospective. La taille des échantillons allait de 17 à 1 501 434 bébés. Une étude cas-témoin a montré une association entre l'exposition prénatale à l'ondansétron et la fente palatine, et une étude de cohorte a mis en évidence un risque accru de malformations cardiovasculaires. Ces résultats n'ont pas été observés dans les autres études.

      Conclusion

      Même si un examen plus poussé de la littérature serait nécessaire, nos résultats indiquent un manque de données associant l'exposition prénatale à l'ondansétron et le risque accru de malformations congénitales. D'autres études épidémiologiques devront être menées pour déterminer si l'ondansétron constitue un traitement efficace et sécuritaire de la nausée, des vomissements et de l'hyperémèse associés à la grossesse.

      Key Words

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