Hypertensive Disorders of Pregnancy Linked to Autism, ADHD

It’s possible hypertensive disorders of pregnancies (HDP) are linked to poor neurodevelopmental outcomes for the offspring, but the role of familial confounding for these associations is not well defined.

A team, led by Judith S. Brand, PhD, examined the link of maternal hypertensive disorders of pregnancy with the risks in offspring for autism spectrum disorders (ASD), attention deficit/hyperactivity disorder (ADHD), and intellectual disability (ID), as well as any variation in the overall cognitive performance in offspring.

The Disorders

HDP is a family of disorders that include both chronic hypertension and de novo hypertension in pregnancy. These disorders impact 5-10% of all pregnant women and are a major cause of perinatal mortality, fetal growth restriction, and preterm birth, with evidence accumulating suggesting they may have long-term neurodevelopmental consequences for the offspring.

“Because placental perfusion is suboptimal in HDP-complicated pregnancies, reduced oxygen and nutritional supplies may be associated with alterations in fetal brain development and subsequent poorer behavioral and cognitive development,” the authors wrote.

The Patient Population

In the Swedish register-based study, the investigators used data from a birth cohort divided into 1.1 million individuals born between 1987-1996 and 285,901 men born between 1982-1992 who attended assessments for military conscription, including a cognitive function test. Each individual from the birth cohort was followed up with until 2014.

The investigators sought main outcomes of the diagnosis of ASDs, ADHD, or ID, which were extracted from the National Patient Register. They assessed cognitive function using written tests summarized it as a single 9-point score.

They also performed whole-cohort and within-sibship analysis, which accounted for unmeasured familial confounding factors shared by siblings.

Findings

The overall prevalence of maternal HDP was 4.0% in the 1987-1996 cohort (n = 42,980) and 5.1% in the military conscription cohort (n = 14,515).

In addition, 15,858 participants were diagnosed with an ASD, 36,852 individuals received a diagnosis of ADHD, and 8454 patients received a diagnosis of ID.

The mean cognitive score among males in the conscription cohort was 5.1 (1.9).

HDP were associated with offspring ASDs in the whole-cohort analyses with multivariable adjustment (HR, 1.22; 95% CI, 1.13-1.31), as well as ADHD (HR, 1.10; 95% CI, 1.05-1.16) and ID (HR, 1.39; 95% CI, 1.27-1.53).

After the investigators compared siblings discordant for HDP, the analysis was less statistically powered but still indicated estimated of similar magnitude for ASDs (HR, 1.19; 95% CI, 1.00-1.42) and possibly ADHD (HR, 1.09; 95% CI, 0.95-1.24), but not for ID (HR, 1.04; 95% CI, 0.83-1.29).

Hypertensive disorders of pregnancy was also linked to somewhat lower cognitive scores in whole-cohort analysis (mean difference comparing offspring exposed with those unexposed, −0.10; 95% CI, −0.13 to −0.07).

However, in the within0sibship analysis, the association was null (mean difference, 0.00; 95% CI, −0.09 to 0.08).

“The study results suggest that HDP are associated with small increased risks of ASDs and possibly ADHD in offspring, whereas associations with ID and cognitive performance are likely confounded by shared familial (environmental or genetic) factors,” the authors wrote.

The study, “Association Between Hypertensive Disorders of Pregnancy and Neurodevelopmental Outcomes Among Offspring,” was published online in JAMA Pediatrics.