Antiemetic use during pregnancy and child neurodevelopment: population-based birth cohort study

Antiemetics are commonly prescribed for nausea and vomiting during pregnancy (NVP), affecting up to 80% of pregnant women. However, data on their long-term neurodevelopmental effects are limited. We therefore aimed to assess the risk of neurodevelopmental disorders and delays in children exposed to antiemetics commonly prescribed during pregnancy.

This nationwide cohort study, designed to emulate a pragmatic trial, used South Korea's National Health Insurance Service mother-child linked database, 2009-2023. The primary exposure of interest was metoclopramide, while pyridoxine, doxylamine, dimenhydrinate, domperidone, and ondansetron were included in secondary analyses. Non-exposed pregnancies within the cohort served as comparators. The outcomes included seven neurodevelopmental disorders-autism spectrum disorder, cerebral palsy, communication disorder, intellectual disorder, movement disorder, attention deficit hyperactivity disorder (ADHD), and epilepsy-as well as neurodevelopmental delays assessed using the validated Korean Developmental Screening Test. Overlap weights based on potential confounders were applied to a Cox proportional hazard model to estimate hazard ratios (HR) with 95% confidence intervals (CI).

Among 630,904 children included, 281,476 (44.6%) were exposed to metoclopramide during pregnancy, while 131,837 (20.9%), 1383 (0.2%), 12,013 (1.9%), 14,531 (2.3%), and 5673 (0.9%) were respectively exposed to pyridoxine, doxylamine, dimenhydrinate, domperidone, and ondansetron. There was no substantial association between antiemetic exposure during pregnancy and neurodevelopmental disorders and delays. Findings were consistent across various subgroup and sensitivity analyses, except for a slightly elevated risk of attention-deficit hyperactivity disorder (HR 1.12, 95% CI 1.06-1.18) in children exposed to metoclopramide during the second half of pregnancy and neurodevelopmental delays in those exposed to metoclopramide for ≥ 7 days.

This large-scale study found no association between antiemetic exposure during pregnancy and the risk of neurodevelopmental disorders or delays in children, providing reassurance for the use of antiemetics in pregnancy to treat nausea and vomiting. However, the slightly elevated risks observed in certain subgroups warrant further investigation. Meanwhile, these findings may assist in guiding decisions when considering antiemetic treatment during pregnancy.