Urban environment in early-life and brain morphology in preadolescents.

Rapid urbanization leads to increased exposure to air pollution, limited greenness, and denser built environments. However, evidence on how these urban factors influence brain development remains limited. We investigated associations between urban characteristics during pregnancy and childhood and brain morphology in preadolescence. The study included 2895 children from the Dutch Generation R Study, with replication in 92 children from the French PELAGIE cohort. Twelve built environment and four urban natural space indicators were estimated at residential addresses during pregnancy and childhood. Brain outcomes included cortical gray matter, cerebral white matter, cerebellum, corpus callosum, subcortical structures volumes, cortical thickness, and surface area assessed at 9-12 years. We applied multi-exposure regression models with data-driven variable selection and assessed mediation by air pollution and road-traffic noise, adjusting for confounders. In Generation R, higher NDVI during pregnancy was associated with smaller cortical gray matter volume (-5132 mm3; 95 % CI: -8611, -1652), and higher facility richness with larger nucleus accumbens volume. During childhood, higher distance to blue space was associated with larger cortical gray matter volume, and higher transport land use with smaller hippocampus. No mediation by air pollution or road-traffic noise was observed. In PELAGIE, associations were consistent but not statistically significant. Cortical thickness was associated with several built environment indicators during childhood, and surrounding greenness was linked to smaller surface area in specific cortical regions. Our findings suggest that early-life exposure to urban environments may influence brain morphology, with distinct contributions from green space, blue space, and built environment factors.