Association between prenatal exposure to antihypertensive medication and neurodevelopmental and educational outcomes in children

Abstract

Abstract Hypertensive disorders of pregnancy (HDP) require medication but neurodevelopmental consequences of prenatal exposure to antihypertensive medication are unclear. We linked five national health and education databases to conduct a cohort study of 179,024 children born in Wales between 2009 and 2016 and investigated associations between maternal HDP and antihypertensive medication and educational and neurodevelopmental outcomes, adjusting for sociodemographic, maternal, and pregnancy confounders. Among, 3,440 (1.9%) mothers who had HDP or who received antihypertensive medication during pregnancy; 629 (0.3%) had treated HDP, 950 (0.5%) untreated HDP, and 1861 (1.0%) received antihypertensive medication without documented HDP. 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, 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). 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.