Serum PFAS Concentrations and Neuromorphometry in Adolescents: The HOME Study

Per- and polyfluoroalkyl substances (PFAS) are a ubiquitous class of persistent synthetic chemicals used in consumer and commercial products for decades. PFAS crosses the blood-placenta and blood-brain barriers to accumulate in the fetus, but the impact on neuroanatomy in early adolescence is unknown. We estimated the association of gestational and early adolescent PFAS concentrations with brain morphometry in 155 participants of the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort enrolled from 2003 to 2006. We measured serum PFAS concentrations during gestation and at age 12. We acquired high resolution anatomical brain MRI to quantify global and regional volumes, cortical thickness and sulcal depth using morphometric methods at age 12. We used a general linear model framework with adjustment for adolescent biological sex, race, household income, maternal IQ, maternal pre-pregnancy BMI, primipara, and total intracranial volume. A doubling in age 12 perfluorooctanoic acid (PFOA) f 2 = 0.06, β = 10.79, (95% CI: 3.45, 18.13), p=0.04 and perfluorononanoic acid (PFNA) f 2 = 0.04, β = 6.14, (95%CI: 1.09, 11.18), p=0.018 concentrations were positively associated with total gray matter volume. A doubling in age 12 PFOA f 2 = 0.04, β = -8.49, (95%CI: -15.28, -1.69), p=0.015 and perfluorooctanesulfonic acid (PFOS) f 2 = 0.03, β = -5.00, (95% CI: -9.81, -0.18), p=0.042 concentrations were negatively associated with total white matter volume. A doubling in age 12 PFOA (f 2 = 0.03, β = 0.03, (95% CI: 0.00, 0.06), p=0.034 and PFOS (f 2 = 0.03, β = 0.02, (95% CI: 0.00, 0.04), p=0.035 concentrations were positively associated with whole brain average cortical thickness. A doubling in age 12 PFOA was positively associated with regional gray matter volumes up to 0.05 mm 3 within cortical, subcortical and deep gray matter, and cortical thickness up to 0.1 mm predominately within the posterior cortex, respectively. No significant associations were observed for gestational PFAS concentrations and brain morphometry. Higher PFAS concentrations are concurrently associated with larger structural volumes and cortical thickness. The significance is uncertain but are consistent with delayed maturation processes delaying synaptic pruning. • Age 12 PFAS concentrations are associated with global and regional brain morphometry. • Age 12 PFOA concentrations are associated with larger global gray matter volumes. • Regional cortical volume increases up to 0.5 mm 3 with doubling of PFOA concentration. • Age 12 PFOA concentrations are associated with larger global cortical thickness. • Age 12 PFOA concentrations are associated with smaller global white matter volume.