Exposure to multiple ambient air pollutants changes white matter microstructure during early adolescence with sex-specific differences

Air pollution is ubiquitous, yet questions remain regarding its impact on the developing brain. Large changes occur in white matter microstructure across adolescence, with notable differences by sex. We investigate sex-stratified effects of annual exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) at ages 9–10 years on longitudinal patterns of white matter microstructure over a 2-year period. Diffusion-weighted imaging was collected on 3T MRI scanners for 8182 participants (1–2 scans per subject; 45% with two scans) from the Adolescent Brain Cognitive Development (ABCD) Study®. Restriction spectrum imaging was performed to quantify intracellular isotropic (RNI) and directional (RND) diffusion. Ensemble-based air pollution concentrations were assigned to each child’s primary residential address. Multi-pollutant, sex-stratified linear mixed-effect models assessed associations between pollutants and RNI/RND with age over time, adjusting for sociodemographic factors. Here we show higher PM2.5 exposure is associated with higher RND at age 9 in both sexes, with no significant effects of PM2.5 on RNI/RND change over time. Higher NO2 exposure is associated with higher RNI at age 9 in both sexes, as well as attenuating RNI over time in females. Higher O3 exposure is associated with differences in RND and RNI at age 9, as well as changes in RND and RNI over time in both sexes. Criteria air pollutants influence patterns of white matter maturation between 9–13 years old, with some sex-specific differences in the magnitude and anatomical locations of affected tracts. This occurs at concentrations that are below current U.S. standards, suggesting exposure to low-level pollution during adolescence may have long-term consequences. Air pollution is known to affect health, but it is unclear whether it affects the growing human brain. We investigated whether there were differences in the development of white matter connections, which allow for faster communication between different brain regions, in children aged 9-13 years living in areas with relatively low or high air pollution in the USA. In a large group of U.S. teens, we find that polluted air is linked to differences in white matter at ages 9-10 years old and over the next two years. In some cases, males and females showed differences in the part of the brain showing changes and the amount of white matter change. Our study suggests that air pollution levels that are deemed acceptable under current regulations in the USA could have long-term effects on how a child’s brain grows. Further studies are needed to better understand the impact of these changes. Cotter et al. investigate associations between low levels of ambient pollutant exposure and white matter microstructural development during the transition from childhood to adolescence. There are sex-stratified associations, with NO2 primarily affecting females and O3 affecting both sexes over time.