Hypertension in Pregnancy Related to Risk of ADHD in Child

Mothers who experienced a hypertensive disorder such as eclampsia during pregnancy reported an almost twofold increased risk of attention-deficit/hyperactivity disorder (ADHD) in their children.

A new analysis from the Millennium Cohort Study (MCS) of over 13,000 mother-child pairs, suggested their association remained even after analysis for multiple potential confounders, including: maternal demographics and health, smoking or alcohol consumption during pregnancy, parity, duration of term, and birth weight.

While there has been strong evidence that ADHD can be inherited, with several genetic variants implicated, the investigators considered whether a gene-environment interaction in utero could also contribute to this increase. The team also posited whether fetal exposure to a hypertensive disorder of pregnancy posed such risk.

"Given that the in utero environment is a critical determinant of neurodevelopmental outcome, a number of pre- and perinatal risk factors have been suggested to increase the risk of ADHD in affected children," explained Ali Khashan, PhD, Department of Epidemiology and Public Health, University College Cork, Cork, Ireland, and colleagues.

The MCS was initiated in the United Kingdom in 2001, with families surveyed when the child was 9 months of age, and again at age 3, 5, 7, and 11 years of age. The presence of a hypertensive disorder of pregnancy was determined from questioning about problems during pregnancy, including terms such as "raised blood pressure" and "eclampsia" or "preeclampsia".

The survey included the question of whether a diagnosis of ADHD had been received from a health professional, and provided the Strength and Difficulties Questionnaire (SDQ) to ascertain parent-reported behavioral difficulties. A score of seven points or greater on the 10 point SDQ subscale on hyperactivity issues provided additional indication of the disorder.

The investigators found a significant association between a hypertensive disorder of pregnancy and ADHD in the offspring, with odds ratio (OR) of 1.89 (95% confidence interval [CI] =1.11-3.2) overall, and OR of 1.78 (CI=1.03-3.07) after controlling for a range of potential confounders. There was no association between the hypertensive disorder of pregnancy and abnormal SDQ scores, although the prevalence of abnormal SDQ and hyperactivity scores were more than sevenfold among children with an ADHD diagnosis than without.

A separate analysis excluding women with chronic hypertension preceding the pregnancy reduced the association slightly, indicating that chronic hypertension may have contributed to a small degree. Khashan and colleagues emphasized; however, "pregnancy-specific conditions were responsible for the majority of the relationship."

Possible mechanisms suggested by the investigators include neuroanatomical alterations, which have been described in children from pregnancies complicated by preeclampsia and have occurred in regions implicated in ADHD. They also considered possible alterations in the maternal inflammatory pathway, speculating that dysregulation in maternal interleukin-17a (IL-17) could be a molecular link between a hypertensive disorder in pregnancy and increased risk of ADHD in the offspring.

The report from the Millennium Cohort Study, “The Effect of Hypertensive Disorders of Pregnancy on the Risk of ADHD in the Offspring,” was published on-line February 4 in the Journal of Attention Disorders

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