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

Maternal immune activation (MIA) and preterm birth have both been associated with increased risk of autism spectrum disorder but their combined impact in preterm children is unclear. This prospective population-based cohort study used data from the French EPIPAGE-2 study, which included liveborn infants delivered at 22 to 34 weeks’ gestation in 2011 and followed them to 5 years of age. Neurodevelopmental outcomes at 2 years’ corrected age and at 5 years were assessed. Among 3609 children (155 [4.3%] exposed), maternal autoimmune diseases were initially associated with more impaired personal-social skills on the Ages & Stages Questionnaire at 2 years and a lower prevalence of high Social Communication Questionnaire scores at 5 years, but these associations were no longer statistically significant after adjustment. No significant associations were found between maternal autoimmune diseases and global developmental delay, ASD risk, or behavioral difficulties at 2 or 5 years in adjusted analyses. Subgroup analyses by gestational age and by exposure to immunosuppressive therapy also showed no increased risk. In this national preterm birth cohort, maternal autoimmune diseases during pregnancy were not associated with increased early behavioral or social communication difficulties in offspring, suggesting that, in the context of contemporary antenatal care, such conditions may not confer additional early neurodevelopmental risk beyond that related to prematurity itself.