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 (∑DEHP: 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 ∑DINCH exposure was associated with higher WMV (2.27 cm3, 95% CI: 0.29, 4.25). We observed significant sex interactions for ∑DEHP with GMV (p-interaction=0.03) and ∑DINCH 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.

The authors have declared no competing interest.

This research was supported in part by the Intramural Research Program of the NIH, EPA (RD-84021901), NIH/NIEHS (R01 ES033518, P30 ES010126, K99 ES035123), and a University of North Carolina, Gillings School of Global Public Health "Gillings Innovation Lab" award. The Baby Connectome Project was funded by U01 MH110274.

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Ethics committee/IRB of the University of North Carolina at Chapel Hill gave ethical approval for this work

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