Traffic-related air pollution links with attention deficit hyperactivity disorder in Denmark: Developmental periods of susceptibility and sex-specificity.

Literature supports that higher early life exposure to air pollution arising from combustion, e.g., traffic exhaust and electric power generation, is associated with attention deficit hyperactivity disorder (ADHD). However, little is known about whether certain periods of exposure during fetal or childhood brain development are more important, i.e. whether there are critical windows of exposure, or whether associations differ by child sex. To address these gaps, we performed a population-based case-cohort study including singletons born 1981-2008 using Danish national registry data resources. We included 21,860 persons diagnosed with ADHD (ICD10 F90.0) and 32,041 persons randomly selected from the eligible population. Daily fine particulate matter (PM2.5) and elemental carbon (EC) exposure corresponded to complete residential addresses from pre-conception through the 12th year of life, using the multi-level Danish air model, DEHM/UBM/AirGIS, at the address level. We estimated hazard ratios (HR) and 95% confidence intervals for pollutants and ADHD, adjusting for urbanicity, Danish region, birth year, sex assigned at birth, socio-demographic factors, and polygenic scores for ADHD. To account for correlation structure of pollutants across time, we adjusted pollutant exposure in one time period for other periods, finding that HRs in the second-year of life were larger than during pregnancy or other postnatal years: EC > 1.13 vs. EC < 0.49 μg/m3 HR: 1.24 (1.12, 1.36); these associations were not attenuated after adjusting for PM2.5. For females, the EC HR in the 2 nd year of life: 1.44 (1.21, 1.72) was larger than for males: 1.18 (1.00, 1.40) (modification test p = 0.000), suggesting increased vulnerability in females. Critical period and sex modification results were similar for PM2.5. These results add to growing literature that major air pollutants increase ADHD risk and add important new insights that early childhood may be an important period of exposure and links may be stronger in females.