Prenatal exposure to endocrine disrupting chemicals and brain development in adolescents

Background and Aim Despite growing concerns regarding the neurotoxicity of phthalates and bisphenols, brain differences associated with gestational exposure to these chemicals are understudied. We investigated the extent to which prenatal exposures to these endocrine disrupting chemicals are associated with global brain volumetric measures in adolescents and whether brain measures mediate the association of prenatal exposures with child IQ. Methods We included 908 mother-child pairs from Generation R, a population-based birth cohort, with data on maternal gestational phthalate and/or bisphenol concentrations and T1-weighted magnetic resonance imaging in children at age 10 years. Child IQ was assessed at age 14 years. Maternal urinary concentrations of phthalate metabolites and bisphenols were measured at early, mid-, and late pregnancy. We examined the associations of pregnancy-averaged, creatinine-adjusted concentrations of individual phthalate metabolites as well as ∑di-2-ethylhexyl phthalate, phthalic acid, and bisphenol A with and brain volumetric measures using linear regression. We used mediation modelling to identify the proportion mediated by brain measures in the association of prenatal exposures and child IQ. Results Higher maternal concentrations of monoethyl phthalate (mEP) were associated with smaller total gray matter volumes in offspring at age 10 years (β per log10 increase in creatinine adjusted mEP=-10.27, 95%CI:-17.85, -2.69). Total gray matter volumes partially mediated the association between higher maternal mEP and lower child IQ (natural indirect effect=-0.27, 95%CI: -0.55,0.00, proportion mediated=20%). An association of higher monoisobutyl phthalate (mIBP) and smaller cerebral white matter volumes was present only in girls, with cerebral white matter volumes mediating the association between higher maternal mIBP and lower IQ in girls. We found no association between maternal prenatal bisphenols and global brain volumetric measures or child IQ. Conclusions Our findings suggest the global impact of prenatal phthalate exposure on the brain that extends into adolescence and underlies impaired general cognition. Keywords: MRI; Pregnancy, phthalates