Hypertensive disorders of pregnancy may impair childhood neurodevelopment

Hypertensive disorders of pregnancy (HDPs) appear to increase the odds of adverse neurodevelopmental and cognitive outcomes, such as autism and attention-deficit/hyperactivity disorder (ADHD), in the offspring, suggest the results of a meta-analysis.

The mechanisms driving these associations remain unclear, but the findings point to a group of children who will benefit from early intervention and support to improve their neurodevelopmental outcomes, according to the investigators.

A total of 13,419 records were screened, and 121 studies reporting outcomes of 29,649,667 offspring met the eligibility criteria. Of these, 85 were cohort studies, 30 case-control, four cross-sectional, and two were secondary analyses of randomized trials. [PLoS Med 2025;22:e1004558]

Compared with unaffected pregnancies, HDPs significantly correlated with a higher unadjusted likelihood of autism spectrum disorder (odds ratio [OR], 1.27, 95 percent confidence interval [CI], 1.49–1.83; p<0.001) and ADHD (OR, 1.27, 95 percent CI, 1.21–1.33; p<0.001) in the offspring.

HDPs also appeared to result in intellectual disability (OR, 1.77, 95 percent CI, 1.31–2.38; p<0.001), global developmental delay (OR, 1.77, 95 percent CI, 1.21–2.59; p<0.001), and reduced mean intelligence (mean difference, –2.20, 95 percent CI, –3.35 to –1.06; p<0.001).

Of note, the associations of hypertension with autism and global development delay no longer reached significance following adjustments for gestational age and birthweight. On the other hand, the association with intelligence quotient, but not with gestational age, remained significant after adjusting for birthweight.

“Adjusted analyses for ADHD and intellectual disability could not be performed due to a lack of suitable studies,” the investigators said. 

Sensitivity analyses revealed consistent results after excluding papers with high risk of bias.

“Our findings are consistent with previous reviews suggesting increased risks of autism spectrum disorder and ADHD,” the investigators said. “We saw no increased likelihood of cerebral palsy, consistent with one previous review.” [JAMA Psychiatry 2018;75:809-819; Pregnancy Hypertens 2023;33:22-29; Children (Basel) 2022;9:385]

These results must be interpreted with caution given the possible role of mediators in the association between hypertension and childhood development.

"We identified gestational age at birth and birthweight as two key mediators,” the investigators said. [Pregnancy Hypertens 2020;21:1-6; JAMA Netw Open 2023;6:e2321165; BMJ Open 2020;10:e031916; Childs Nerv Syst 2010;26:1139-1149]

“It is plausible that the observed association between hypertension and poor neurodevelopmental outcomes may in fact be driven by the increased rates of preterm birth and low birthweight in this cohort,” they added. 

Further studies should consider using individual participant data meta-analysis to allow further investigation, according to the researchers. “There was a paucity of relevant literature which accounted for key mediating and confounding factors, thus highlighting an avenue for future research,” they said.

Eligible studies

In this systematic review and meta-analysis, the databases of Medline, CINAHL, Web of Science, and PsycINFO were searched from inception through 18 September 2024 for studies on neurodevelopmental, cognitive, or educational outcomes for children born following HDPs. 

Two reviewers independently screened records, extracted data, and assessed quality of studies using Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A random-effects meta-analysis model was used to pool studies reporting similar outcomes.

"This study is limited by a lack of constituent papers which adjusted for confounding and mediating factors, a high amount of heterogeneity among included studies, and possible publication bias for some outcomes,” the investigators said.