February 2025
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Objective: Prenatal phthalate exposure is associated with adverse neurodevelopmental outcomes, yet data on impacts of early life exposure remains limited. We investigated phthalate and replacement plasticizer exposures from 2 weeks to 7 years of age in relation to brain anatomical attributes, using serial structural magnetic resonance imaging (sMRI). Material and Methods: Children were enrolled after birth into the UNC Baby Connectome Project, a longitudinal neuroimaging study. Urine samples (n=406) were collected at each visit and analyzed for 17 phthalate and replacement plasticizer metabolites. Among 157 children contributing 369 sMRIs, we calculated metabolite-specific average exposures across each individual's urine samples and used linear mixed models to estimate longitudinal associations of log transformed, specific gravity-adjusted average metabolite concentrations with gray (GMV) and white matter (WMV), and cortical volume (CV), thickness (CT), and surface area (CSA). We examined sex-specific differences in these associations. Results: Higher average metabolite concentration was associated with lower GMV (MCPP: (-1.73 cm3, 95% CI: -3.36, -0.10) and higher WMV (ΣDEHP: 2.28 cm3, 95% CI: 0.08, 4.48). Among boys (n=72, 140 sMRIs), MEP (-2.97 cm3, 95% CI: -5.85, -0.09) and MiBP (-2.40 cm3, 95% CI: -4.64, -0.15) were also associated with lower GMV. Among girls (n=85, 229 MRIs), higher ΣDINCH exposure was associated with higher WMV (2.27 cm3, 95% CI: 0.29, 4.25). We observed significant sex interactions for ΣDEHP with GMV (p-interaction=0.03) and ΣDINCH with WMV (p-interaction=0.001). Conclusion: Early life phthalate/plasticizer exposure may differentially impact various brain region volumes in early childhood, with potential downstream consequences on functional development.