A recent cohort study involving over 1.1 million children in Denmark found that associations between maternal health during pregnancy and autism may be attributable to familial confounding.

In the study, published in Nature Medicine, investigators tested 236 maternal diagnoses and observed significant associations with autism.

Fifteen chronic and 15 nonchronic conditions associated with autism were found. Examples of chronic conditions include psychotropic drug use, injuries to the ankle, foot, or toe, an eye injury, and a fracture to the skull. Examples of nonchronic conditions include menstrual pain, asthma, pulmonary embolism, primary hypertension, and patella disorder.

By the end of the study period, 1.6% of the children (n = 18,374) involved in the study were diagnosed with autism. Despite pervasive associations across 30 maternal conditions, the investigators emphasized that familial genetics and shared environments, largely explained these findings.

"Our findings indicate pervasive associations between maternal health in pregnancy and offspring autism and underscore that these associations are largely attributable to familial confounding," wrote lead study author Vahe Khachadourian, of the Department of Child and Adolescent Psychiatry at the New York University Grossman School of Medicine.

Using Cox proportional hazard regression models, the investigators controlled for factors like comorbidity, disorder chronicity, and sociodemographic differences. A sibling discordance analysis further supported the role of familial confounding. Paternal negative control designs confirmed that familial correlations accounted for many observed associations between maternal health and autism.

"There is a need to validate these conclusions in external datasets and investigate the role of different familial confounders—including both genetic and nongenetic factors—in driving these associations, they concluded.

The authors reported no conflicts of interest related to the study.