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

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.

Figure 1.. Flow Diagram of Studies Selected for Inclusion in the Systematic Review

ADHD indicates attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder. ^aAn additional 6 studies are also included for ASD and 1 for ADHD.

Figure 2.. Forest Plot for Studies of the Association of Hypertensive Disorders of Pregnancy (HDP) With Autism Spectrum Disorder (ASD)

Odds ratios (ORs) are calculated using random-effects analysis. The generic inverse variance method was used to include studies that do not report raw data. Diamonds indicate effect size; size of markers, 95% CI. HBP indicates high blood pressure.

Figure 3.. Forest Plot for Studies of the Association of Hypertensive Disorders of Pregnancy (HDP) With Attention-Deficit/Hyperactivity Disorder (ADHD)

Odds ratios (ORs) are calculated using random-effects analysis. The generic inverse variance method was used to include studies that do not report raw data. Diamonds indicate effect size; size of markers, 95% CI.