Maternal hypertensive disorders of pregnancy and childhood neurodevelopmental disorders: A two‐sample Mendelian randomization

OBJECTIVE: To investigate the association between maternal hypertensive disorders of pregnancy (HDP) and childhood neurodevelopmental disorders (NDD) by Mendelian randomization (MR). METHODS: A two-sample MR analysis was conducted to evaluate the causal effects of HDP, including gestational hypertension (GH), pre-eclampsia superimposed on chronic hypertension, and pre-eclampsia or eclampsia on childhood NDD, such as cerebral palsy (CP), autism spectrum disorder (ASD), and hyperkinetic disorders (HD). The exposure and outcome data were extracted from the FinnGen database. As the genetic and phenotypic data used were from previously collected resources, the analysis of FinnGen data in this study was a retrospective study. RESULTS: The two-sample MR analysis did not identify a significant causal relationship between maternal HDP and childhood NDD: GH with CP (odds ratio [OR] 1.05, 95% confidence interval [CI] 0.81-1.35), ASD (OR 1.04, 95% CI 0.83-1.29), and HD (OR 1.02, 95% CI 0.91-1.15); pre-eclampsia superimposed on chronic hypertension with CP (OR 1.03, 95% CI 0.88-1.21), ASD (OR 1.02, 95% CI 0.85-1.23), and HD (OR 1, 95% CI 0.94-1.05); pre-eclampsia or eclampsia with CP (OR 1.07, 95% CI 0.82-1.40), ASD (OR 0.90, 95% CI 0.69-1.18), and HD (OR 0.90, 95% CI 0.80-1.01). The MR-Egger intercept did not detect potential pleiotropy (P > 0.05), thereby the results were considered unbiased. CONCLUSIONS: Maternal HDP did not increase the risk of childhood NDD.