Prenatal exposure to antihypertensive medication and neurodevelopmental and educational outcomes

Abstract Background Hypertensive disorders of pregnancy (HDP) require treatment to mitigate maternal and fetal morbidity and mortality, yet the potential neurodevelopmental consequences of prenatal antihypertensive exposure remain unclear. Methods We conducted a population-based cohort study using five linked national health and education records for 179,024 children born in Wales (2009-2016). Generalized estimating equation (GEE) and Cox proportional hazards models examined associations between maternal HDP, antihypertensive medication use, and educational and neurodevelopmental outcomes, adjusting for sociodemographic, maternal, and pregnancy confounders. Results Among, 3,440 (1.9%) mothers with HDP or on antihypertensive medication; 629 (0.3%) had treated HDP, 950 (0.5%) had untreated HDP, and 1,861 (1.0%) received antihypertensive medication without a documented HDP diagnosis. Autistic spectrum disorder (ASD) was associated with prenatal exposure to antihypertensive medication (adjusted OR 1.67, 95% CI 1.26-2.21, p < 0.001), specifically with beta-blockers (adjusted OR 1.96, 95% CI 1.39-2.78). Untreated maternal HDP was not associated with ASD. Learning and communication difficulties were associated with beta-blockers and methyldopa, as well as untreated HDP, suggesting confounding by indication. Neither HDP nor anti-hypertensive medication were associated with attention deficit hyperactivity disorder (ADHD). No associations were found with other classes of antihypertensive medications. Conclusions In this large, unselected cohort, prenatal beta-blocker exposure was associated with ASD independent of maternal hypertension. Further research should be undertaken regarding the biological mechanisms and choice of antihypertensive therapy in pregnancy should be carefully selected to balance maternal benefits and potential neurodevelopmental risks in offspring. Key messages • ASD was associated with prenatal exposure to anti-hypertensive medication; specifically, beta-blockers. • These data should inform physician-patient discussions on antihypertensive medication selection during pregnancy.