Prenatal exposure to PFAS and multimodal structural brain development across childhood

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental pollutants that are posited to be neurotoxic to the developing brain; however, the impact of prenatal exposure to PFAS - particularly to newer, short-chain PFAS - on brain development across childhood is unclear.

Concentrations of 9 PFAS were quantified in cord blood plasma of 452 infants (440 for the diffusion sample) who later participated in structural and diffusion magnetic resonance imaging (MRI) at ages 4.5, 6, 7.5, and 10.5 years, providing estimates of regional cortical thickness and surface area, subcortical volumes, and fractional anisotropy (FA) of key white matter tracts. Longitudinal mixed-effect models estimated associations of PFAS with age 4.5 brain metrics and their developmental trajectories across childhood after correcting for the false discovery rate within PFAS and outcome domains.

Higher concentrations of PFNA and PFDA in cord blood were associated with lower model-estimated age 4.5 surface area of the right paracentral lobule. PFHpA was associated with faster surface area growth in the left rostral anterior cingulate and slower growth in the right caudal middle frontal gyrus from 4.5 to 10.5 years. The short-chain compound PFBS was linked with greater model-estimated age 4.5 FA in 12 white matter tracts, while PFOA and PFNA were linked with lower FA in the middle cerebellar peduncle and the left corticospinal tract, respectively. Associations of PFBS with FA attenuated with age in several tracts.

Prenatal exposure to PFAS was associated with altered development of frontal and paracentral regions and of white matter microstructure. These findings highlight the need for further research examining the long-term associations of prenatal exposure to PFAS with children's neurodevelopment.