Early Life Phthalate Exposure Impacts Gray Matter and White Matter Volume in Infants and Young Children

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 (North Carolina, USA; 2017-2020). 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 and white matter volume, and cortical volume, thickness, and surface area. We examined sex-specific differences in these associations. RESULTS:Higher average metabolite concentration was associated with lower gray matter volume (MCPP: (-1.73 cm3, 95 % CI: -3.36, -0.10) and higher white matter volume (∑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 gray matter volume. Among females (n = 85, 229 MRIs), higher ∑DINCH exposure was associated with higher white matter volume (2.27 cm3, 95 % CI: 0.29, 4.25). We observed significant sex interactions for ∑DEHP with gray matter (p-interaction = 0.03) and ∑DINCH with white matter volume (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.