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Original Investigation
August 2018

Association of Hypertensive Disorders of Pregnancy With Risk of Neurodevelopmental Disorders in Offspring: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Irish Centre for Fetal and Neonatal Translational Research, Cork University Maternity Hospital, University College Cork, Cork, Ireland
  • 2School of Public Health, University College Cork, Cork, Ireland
  • 3Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
  • 4Department of Women’s and Children’s Health, Institute of Translational Medicine, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, England
  • 5Department of Psychiatry, Cork University Hospital, University College Cork, Cork, Ireland
  • 6Alimentary Pharmabiotic Centre, Microbiome Institute, University College Cork, Cork, Ireland
  • 7Division of Population Health Sciences, Department of Epidemiology, Royal College of Surgeons in Ireland, Dublin, Ireland
JAMA Psychiatry. 2018;75(8):809-819. doi:10.1001/jamapsychiatry.2018.0854
Key Points

Question  What are the pooled estimates from existing literature examining the association between hypertensive disorders of pregnancy and neurodevelopmental disorders in offspring?

Findings  Pooled estimates from this systematic review and meta-analysis of 61 studies suggest that exposure to hypertensive disorders of pregnancy is associated with a small yet statistically significant increase in the odds of autism spectrum disorder and attention-deficit/hyperactivity disorder in offspring compared with no exposure.

Meaning  Increased developmental screening of infants exposed to hypertensive disorders of pregnancy could allow for early intervention, which in turn may improve neurodevelopmental outcome.

Abstract

Importance  Although research suggests an association between hypertensive disorders of pregnancy (HDP) and autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and other neurodevelopmental disorders in offspring, consensus is lacking. Given the increasing prevalence of hypertension in pregnancy, it is important to examine the association of HDP with neurodevelopmental outcome.

Objective  To synthesize the published literature on the association between HDP and risk of neurodevelopmental disorders in offspring in a systematic review and meta-analysis.

Data Sources  On the basis of a preprepared protocol, a systematic search of PubMed, CINAHL, Embase, PsycINFO, and Web of Science was performed from inception through June 7, 2017, supplemented by hand searching of reference lists.

Study Selection  Two investigators independently reviewed titles, abstracts, and full-text articles. English-language cohort and case-control studies were included in which HDP and neurodevelopmental disorders were reported.

Data Extraction and Synthesis  Data extraction and quality appraisal were performed independently by 2 reviewers. Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed throughout.

Main Outcomes and Measures  Random-effects meta-analyses of estimated pooled odds ratios (ORs) for HDP and ASD and for HDP and ADHD. Stand-alone estimates were reported for all other neurodevelopmental disorders.

Results  Of 1166 studies identified, 61 unique articles met inclusion criteria. Twenty studies reported estimates for ASD. Eleven of these (including 777 518 participants) reported adjusted estimates, with a pooled adjusted OR of 1.35 (95% CI, 1.11-1.64). Ten studies reported estimates for ADHD. Six of these (including 1 395 605 participants) reported adjusted estimates, with a pooled adjusted OR of 1.29 (95% CI, 1.22-1.36). Subgroup analyses according to type of exposure (ie, preeclampsia or other HDP) showed no statistically significant differences for ASD or ADHD. Thirty-one studies met inclusion criteria for all other neurodevelopmental disorders. Individual estimates reported for these were largely inconsistent, with few patterns of association observed.

Conclusions and Relevance  Exposure to HDP may be associated with an increase in the risk of ASD and ADHD. These findings highlight the need for greater pediatric surveillance of infants exposed to HDP to allow early intervention that may improve neurodevelopmental outcome.

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