Risk of malformation after ondansetron in pregnancy: An updated systematic review and meta-analysis

Birth Defects Res. 2020 Aug;112(13):996-1013. doi: 10.1002/bdr2.1705. Epub 2020 May 18.


Ondansetron is increasingly used off label to treat nausea and vomiting during pregnancy. The main objective of this study was to evaluate the risk of major congenital malformations (MCM), cardiac defects and orofacial clefts associated with first trimester exposure to ondansetron using a meta-analytic approach. MEDLINE, ClinicalTrials.gov and Scopus were searched until November 2019. All comparative cohort and case-control studies on MCM, cardiac or orofacial defects and use of ondansetron during pregnancy were included. A team of paired reviewers independently extracted data using a proprietary collaborative WEB-based meta-analysis platform (metaPreg.org). Pooled odd ratios with corresponding 95% CIs were calculated using random effects models. From 214 records initially retrieved, 12 studies were included. Using all available information to date, first trimester exposure to ondansetron was found to be associated with an increased risk of (a) ventricular septal defects (VSD) (OR 1.11, 95% CI 1.00-1.23; p < .05; n = 6 studies; I2 = 0%) and (b) oral clefts (OR 1.22, 95% CI 1.00-1.49; p < .05; n = 4 studies; I2 = 0%). No significant association was observed for the risk of cleft palate but, when excluding the study that contributed to the study heterogeneity, we found an OR of 1.48 (95% CI 1.19-1.84; p < .01; n = 5 studies; I2 = 0%). No statistically significant association was found for MCM, overall cardiac malformations, atrial septal defects and cleft lip with or without cleft palate. Exploratory investigations of other malformations showed an increased risk of diaphragmatic hernia, hypoplastic left heart and "respiratory system anomalies."

Keywords: cardiac defect; malformations; meta-analysis; ondansetron; orofacial cleft; pregnancy; systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Abnormalities, Drug-Induced* / etiology
  • Antiemetics* / adverse effects
  • Cleft Lip* / chemically induced
  • Cleft Palate* / chemically induced
  • Female
  • Humans
  • Ondansetron / adverse effects
  • Pregnancy


  • Antiemetics
  • Ondansetron