Hypertensive disorders of pregnancy and childhood neurodevelopment: A systematic review and meta-analysis

Background: Hypertensive disorders of pregnancy may be associated with an increased risk of adverse neurodevelopmental outcomes for the child, though no recent comprehensive meta-analyses exist. The aim of this study was to conduct a systematic review and meta-analysis examining the association between hypertensive disorders of pregnancy and child neurodevelopmental disabilities, intelligence, and educational outcomes. Methods and findings: A search was conducted of MEDLINE, CINAHL, Web of Science, and PsycINFO databases from inception until 18 September 2024. Reference lists of included papers were also screened. Observational studies and secondary analyses of randomized trials reporting neurodevelopmental, cognitive, or educational outcomes for children born following hypertensive disorders of pregnancy against a reference population (unaffected pregnancies) were included. Two reviewers independently screened records, extracted data, and assessed quality of studies using Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Studies reporting similar outcomes were pooled using a random-effects meta-analysis model. Outcomes included autism, attention-deficit/hyperactivity disorder, cerebral palsy, global developmental delay, intellectual disability, intelligence quotient, and educational attainment. Results were reported as odds ratios (OR) or mean difference (MD) with corresponding 95% confidence intervals (CI). After screening 13,419 records, 121 studies reporting outcomes of 29,649,667 offspring were included. We included 85 cohort studies, 30 case-control studies, four cross-sectional studies, and two secondary analyses of randomized trials. Compared with unaffected pregnancies, hypertensive disorders of pregnancy were associated with an increased unadjusted likelihood of autism spectrum disorder (OR 1.65 (95% CI [1.49,1.83]); p