Another prospective study on the safety of ondansetron for nausea and vomiting of pregnancy: addressing ongoing concerns

Background The safety of ondansetron for nausea and vomiting in pregnancy (NVP) remains a subject of ongoing debate, driven by conflicting study results and a disagreement between the European Medicines Agency (EMA) and the European Network of Teratology Information Services (ENTIS) regarding its potential fetal risks. Objective To assess the safety of using ondansetron for NVP and its possible association with major birth defects and neonatal outcomes. Methods A prospective cohort study was conducted based on structured telephone follow-ups of women with NVP who contacted the NVP Helpline at a teratology information service (TIS) at the Shamir Medical Center between April 2014 and April 2018. Exposure and clinical characteristics were recorded during the initial consultation, and pregnancy and neonatal outcomes were ascertained after the estimated date of delivery using a validated questionnaire. Women treated with ondansetron formed the exposed group; controls did not receive ondansetron but could use other NVP therapies. Subgroup analyses explored the dose and frequency of use. Results The analysis included 260 women (137 exposed; 123 controls). Baseline characteristics were broadly comparable, except for higher NVP severity in the ondansetron group, reflected by higher PUQE scores (9.86 ± 2.66 vs. 8.59 ± 2.49; p = 0.001) and more frequent antacid use (p = 0.001). Live birth rates (95.6% vs. 94.3%) and birth weights did not differ between groups. No differences were found in neonatal complications. Major congenital malformations were comparable between groups (5.1% vs. 4.1%; p = 0.695), with no consistent pattern identified. Conclusion In this prospective cohort, ondansetron exposure was not associated with increased risk of adverse neonatal outcomes or major congenital malformations. The sample size limits the detection of very rare outcomes, and larger studies remain warranted.