Ondansetron Use in Pregnancy and Birth Defects: A Systematic Review

To examine the risk of birth defects in children born to women who used ondansetron early in pregnancy for nausea and vomiting of pregnancy or hyperemesis gravidarum.

PubMed, EMBASE, Cochrane, Scopus, Web of Science, Journals@Ovid Fulltext, ClinicalTrials.gov, and Google Scholar databases.

Studies were included for review if they were written in English, included a comparison population of patients not exposed to ondansetron, and reported human data, original research, exposure to ondansetron during the first trimester, and structural birth defects as an outcome.

A total of 423 records were identified. After accounting for duplicate records and including only relevant articles, a total of eight records met criteria for review. Data from the various studies were conflicting: whereas the three largest studies showed no increased risk of birth defects as a whole (36 malformations, 1,233 exposed compared with 141 malformations and 4,932 unexposed; 58/1,248 exposed compared with 31,357/895,770 unexposed; and 38/1,349 exposed compared with 43,620/1,500,085 unexposed; with odds ratios [ORs] of 1.12 (95% confidence interval [CI] 0.69-1.82), 1.3 [95% CI 1.0-1.7], and 0.95 [95% CI 0.72-1.26], respectively), two of these studies demonstrated a slightly increased risk of cardiac defects specifically (OR 2.0 [95% CI 1.3-3.1] and 1.62 [95% CI 1.04-2.14]), a finding that was not replicated in other studies. The most consistent association (if any) appears to be a small increase in the incidence of cardiac abnormalities, the bulk of which are septal defects.

The overall risk of birth defects associated with ondansetron exposure appears to be low. There may be a small increase in the incidence of cardiac abnormalities in ondansetron-exposed neonates. Therefore, ondansetron use for nausea and vomiting of pregnancy should be reserved for those women whose symptoms have not been adequately controlled by other methods.