French preterm cohort links maternal autoimmune disease to no significant behavioral risk

Maternal autoimmune diseases during pregnancy were not associated with significantly increased behavioral or social communication difficulties among children born preterm in a prospective analysis of the French EPIPAGE-2 cohort. The study included 3,609 children, of whom 155, or 4.3%, had been exposed to maternal autoimmune disease. Initial associations with selected developmental measures were no longer statistically significant after adjustment, and the researchers found no significant links with global developmental delay, autism spectrum disorder risk or behavioral difficulties at either assessed age.

Researchers used data from the EPIPAGE-2 population-based cohort, which included liveborn infants delivered at 22 to 34 weeks’ gestation in 2011. The children were followed to five years of age, and neurodevelopmental outcomes were assessed at two years’ corrected age and at five years. In unadjusted analyses, exposure to maternal autoimmune disease was initially associated with more impaired personal-social skills on the Ages & Stages Questionnaire at two years and a lower prevalence of high scores on the Social Communication Questionnaire at five years. Neither association remained statistically significant after adjustment.

Adjusted analyses also showed no significant association between maternal autoimmune diseases and global developmental delay, autism spectrum disorder risk or behavioral difficulties at two or five years. Subgroup analyses divided by gestational age and by exposure to immunosuppressive therapy did not identify an increased risk. These subgroup results should be interpreted in light of the small number of exposed children, which limited the statistical precision of the assessments.

The study examined a question arising because maternal immune activation and preterm birth have each been associated with increased autism spectrum disorder risk, while their combined influence in preterm children was unclear. The EPIPAGE-2 findings do not support evidence that maternal autoimmune disease during pregnancy increased the early behavioral or social communication difficulties measured in this cohort. The authors cautioned that the conclusion is not definitive: only 155 children were exposed, the exposed group predominantly included children whose mothers had endocrine autoimmune diseases, and the study lacked immune activation biomarkers. Larger studies with more diverse exposure groups and direct immunological measurements are therefore needed to clarify whether the observed null associations reflect a genuine absence of relationship or limited statistical power.

Subject of Research: Maternal autoimmune disease and neurodevelopmental outcomes in a French cohort of preterm children

Article Title: Exploring the effect of maternal autoimmune diseases on behavioral and social difficulties risk in children born preterm: evidence from EPIPAGE-2 study

Article References: Ellul, P., Marchand-Martin, L., Salmon, F., Ancel, P.-Y., Pierrat, V., & Letouzey, M. (2026). Exploring the effect of maternal autoimmune diseases on behavioral and social difficulties risk in children born preterm: evidence from EPIPAGE-2 study. Translational Psychiatry. https://doi.org/10.1038/s41398-026-04534-0

Image Credits: AI Generated

DOI: 10.1038/s41398-026-04534-0

Keywords: maternal autoimmune disease, preterm birth, EPIPAGE-2, neurodevelopment, behavioral difficulties, social communication, autism spectrum disorder, developmental delay, maternal immune activation, French cohort, Exploring, effect