Prenatal exposure to antihypertensive medication: A systematic review of neurodevelopmental and educational outcomes

Abstract

Background: Where possible, medication is avoided during pregnancy as it can cross the placenta and potentially cause congenital malformations, impair growth and have longer-term functional or cognitive sequelae. However, medication is sometimes required for pre-existing or new-onset conditions such as hypertension disorders during pregnancy; the longer-term outcomes of which remain unclear. This systematic review aimed to synthesise the evidence on prenatal exposure to antihypertensive medication and longer-term neurodevelopmental and educational outcomes up to 18 years of age. Methods: We searched Medline Ovid, PubMed, Excerpta Medica Database, and Web of Science from inception (1946) until 04 July 2025, selecting observational and experimental studies. The inclusion criteria for eligible studies were pregnant women with or without any hypertension disorder of pregnancy, mothers taking antihypertensive medication during pregnancy comparing them with those not exposed, children ≥1 years of age, and children with one of the predefined neurodevelopmental and educational outcomes. The studies' quality was evaluated using the National Heart, Lung, and Blood Institute assessment tool. Results: Of 11 studies included (five cohorts, two case-control and four randomised controlled trials), 10 were of high quality, while only one was of low quality. Six of the 11 studies demonstrated significant associations between prenatal exposure to antihypertensive medication and at least one adverse neurodevelopmental outcome in children. One study reported an increased risk of autism spectrum disorder following calcium channel blockers and beta-blockers exposure, one reported the risk of fine motor problems following calcium channel blockers exposure, one reported increased risk of low intelligence quotient following exposure to methyldopa, one reported an increased risk of attention deficit hyperactivity disorder following exposure to beta-blockers, one reported speech problems following exposure to more than one antihypertensive medications, and one reported an increased risk of sleeping disturbance following exposure to clonidine. Methodological heterogeneity, small sample sizes, and inadequate confounder adjustment were common limitations. Conclusions: The association between prenatal antihypertensive exposure and neurodevelopmental outcomes warrants further research, focusing on the impacts of specific medication classes on a range of outcomes in the same study population.