Shared and disorder-specific prenatal and perinatal risk factors for neurodevelopmental disorders: a nationwide...

Neurodevelopmental disorders (NDDs) are common, frequently co-occur, and impose a substantial burden, yet the extent to which early-life risk factors differ across the spectrum of NDDs remains unclear. Using the EPI-MERES register, derived from the French National Health Data System, we conducted a nationwide cohort study of all 6.8 million children born in France between 2010 and 2018, followed until September 2024. We investigated prenatal and perinatal risk factors, including gestational age, small for gestational age (SGA), neonatal hypoxia, congenital malformations, parental age, maternal alcohol and tobacco exposure, maternal obesity, and socioeconomic disadvantage, in relation to five major NDDs: communication disorders, specific learning disorders, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID). Models were estimated both with and without adjustment for co-occurring NDDs. Overall, 506,505 children (7.5%) were identified with at least one NDD over a median follow-up of 9.6 years. Co-occurrence was frequent, especially for ID (54.5%), ASD (52.2%), and ADHD (34.9%). In models not adjusted for NDD co-occurrence, several factors were common across disorders, including male sex, prematurity, SGA, congenital malformations, maternal obesity, prenatal alcohol and tobacco exposure, and young maternal age. In addition, some exposures showed disorder-specific associations, most notably with ID: extreme prematurity, SGA, congenital malformations, neonatal hypoxia, and advanced parental age. After adjustment for co-occurring NDDs, several associations were attenuated, indicating that some risk factors contribute simultaneously to multiple disorders; for example, the male predominance in ID and the association of extreme prematurity with ASD were substantially reduced. These findings delineate shared and disorder-specific prenatal and perinatal risk profiles and emphasize the importance of considering co-occurring diagnoses in understanding etiological pathways and informing early prevention strategies.