Early life phthalate and replacement plasticizer exposures and changes in early childhood brain functional connectivity and structural morphology

Phthalates and replacement plasticizers (PRPs) are ubiquitous exposures in daily life across all age ranges. Exposure to phthalates has been linked to changes in cognitive and behavioral development and associated with increased risk of some developmental disabilities. We examined the extent to which early life exposure to PRPs was associated with changes in connection strength of resting state functional networks or impacted structural morphologies of cortical regions of interest that underlie basic and higher order cognitions. We utilized the UNC Chapel Hill enrollment in the Baby Connectome Project, a longitudinal study of normative brain development of children between 2 weeks and 5 years of age. Non-sedated structural and resting state functional magnetic resonance imaging of the brain during natural sleep were obtained longitudinally, along with urine samples that were analyzed for 17 PRP metabolites. Using kernal weighted estimating equations and generalized linear models, we identified multiple PRP metabolites were associated with alterations in within-network connection strengths in the executive control and dorsal attention networks, with directionality often differing between boys and girls. PRP exposure among boys tended to be associated with lower functional connectivity, whereas PRP exposure among girls tended to be associated with higher functional connectivity. Among girls, MiBP metabolite concentrations were also significantly associated with cortical thinning in several regions of interest in the temporal lobe. Our results indicate that exposure to PRPs in early life has a measurable impact on the developmental trajectory of brain maturation, with potentially important differences by child sex.