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

Irina Tolchinsky; Maayan Beckinshtein; Elkana Kohn; Rana Cohen; Tal De-Haan; Tomer Ziv-Baran; David Stepensky; Itai Gueta; Matitiahu Berkovitch; Maya Berlin

doi:10.3389/fphar.2026.1783632

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

Front Pharmacol. 2026 Mar 10:17:1783632. doi: 10.3389/fphar.2026.1783632. eCollection 2026.

Authors

Affiliations

¹ Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
² Clinical Pharmacology and Toxicology Unit, Shamir (Assaf Harofeh) Medical Center, Zerifin, Affiliated to the Gray Faculty of Medical & Health Sciences, Tel-Aviv University, Tel Aviv, Israel.
³ School of Public Health, the Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel.
⁴ Department of Internal Medicine F, The Clinical Pharmacology Unit, Tel-Aviv Medical Center, Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
⁵ The Andy Lebach Chair of Clinical Pharmacology and Toxicology, The Gray Faculty of Medical & Health Sciences, Tel-Aviv University, Tel Aviv, Israel.

Abstract

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.

Keywords: EMA (european medicines agency); ENTIS (european network of teratology information services); HG (hyperemesis gravidarum); NVP (nausea and vomiting of pregnancy); major malformations; ondansetron.