A Scoping Review of 5‐ <scp> HT ₃ </scp> Antagonist Antiemetic Medication Safety in the Management of Nausea and Vomiting of Pregnancy

ABSTRACT Purpose The prescribing of 5‐hydroxytryptamine 3 receptor and type 3 serotonin receptor (5‐HT 3 ) antagonists, particularly ondansetron, for nausea and vomiting in pregnancy (NVP) has increased globally. However, evidence on the safety of these medications in pregnancy remains unclear. This review aims to examine the available literature surrounding the safety of 5‐HT 3 antagonist medication use for NVP. Methods Embase, Ovid Medline, Global Health, and CINAHL were searched from inception to 20 March 2024, updated on 7 May 2025. Full‐text, original articles available in English, examining the use of 5‐HT 3 antagonist medications (ondansetron, granisetron, tropisetron, dolasetron, palonosetron, ramosetron) for NVP were included. Any maternal, neonatal, or child health outcomes were of interest. Results Results were screened and extracted using Covidence and synthesized in Excel. The search strategy returned 1942 articles of which 39 unique, full‐text studies were included. Most papers examined ondansetron (34/39 papers, 87%) with limited evidence for granisetron (5/39 papers, 13%). Ondansetron use for NVP yielded minimal complications for maternal health and late pregnancy outcomes. No elevated risk of any congenital anomalies overall was observed. Although the risks of cardiac and orofacial anomalies were conflicting, the absolute changes in risk are minimal for either anomaly, especially considering potential confounding from study methodology and limited sample sizes. Conclusion Ondansetron likely poses low risk of harm to maternal and neonatal health, especially considering the excess risks of untreated NVP; however additional research is required for certain congenital anomalies. Further investigation is also warranted into granisetron safety before its widespread use during pregnancy.