A1 Refereed original research article in a scientific journal

Maternal hypertensive disorders and neurodevelopmental disorders in offspring: a population-based cohort in two Nordic countries




AuthorsWang Hui, László Krisztina D., Gissler Mika, Li Fei, Zhang Jun, Yu Yongfu, Li Jiong

PublisherSPRINGER

Publication year2021

JournalEuropean Journal of Epidemiology

Journal acronymEUR J EPIDEMIOL

Volume36

Issue5

First page 519

Last page530

Number of pages12

ISSN0393-2990

eISSN1573-7284

DOIhttps://doi.org/10.1007/s10654-021-00756-2

Web address https://link.springer.com/article/10.1007/s10654-021-00756-2

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/58943289


Abstract
Maternal hypertensive disorders during pregnancy (HDP) have been associated with neuropsychiatric problems in offspring. We aim to investigate the associations between specific types of maternal HDP and offspring neurodevelopmental disorders and further examine whether the timing of onset and severity of HDP would affect these associations. The study population consisted of 4,489,044 live-born singletons in Denmark during 1978-2012 and Sweden during 1987-2010. Maternal HDP was categorized into chronic hypertension, gestational hypertension, and pre-eclampsia; pre-eclampsia was further stratified according to timing (early-onset, late-onset), or severity (moderate, severe) of the disease. Neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID), were defined by ICD-coded register diagnosis. Cox regression was used to calculate hazard ratios (HR) while adjusting for potential confounders, and sibling analyses assessed the influence of unmeasured shared familial factors. Maternal HDP was associated with increased risks of ADHD (HR, 1.24; 95% confidence interval [CI], 1.20-1.28), ASD (1.29 [1.24-1.34]), and ID (1.58 [1.50-1.66]) in offspring, respectively, which was mostly driven by pre-eclampsia. The strongest associations were observed for early-onset and severe pre-eclampsia, and the corresponding HRs for ADHD, ASD and ID were 1.93 [1.73-2.16], 1.86 [1.61-2.15], and 3.99 [3.42-4.65], respectively. The results were similar in the sibling analyses. The associations between maternal HDP and offspring neurodevelopmental disorders were consistent across the subgroups of sex, preterm status, parity, maternal age and psychiatric disorders. Maternal HDP, especially early-onset pre-eclampsia, are associated with increased risks of ADHD, ASD, and ID in particular, independent of shared familial factors.

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