Associations of Legacy and Emerging Halogenated Flame Retardant Exposures with Childhood Attention Deficit/Hyperactivity Disorder-Related Traits and Brain Functional Connectivity in a Canadian Birth Cohort

Halogenated flame retardants (HFRs) are widely used chemicals with potential neurotoxicity, yet limited epidemiologic evidence exists for their association with childhood neurodevelopment. We investigated associations between HFR exposures and attention-deficit/hyperactivity disorder (ADHD)-related traits and brain functional connectivity in 194 children aged 8-12 years from the GESTation and Environment (GESTE) birth cohort in Sherbrooke, Canada. We assessed 16 legacy and emerging HFRs in plasma and stool, with 5 in plasma and 9 in stool samples included in the final analysis. ADHD-related traits were assessed using behavioral questionnaires and the Conners Continuous Performance Test. Resting-state functional magnetic resonance imaging was used to assess brain functional connectivity in four ADHD-relevant brain networks. We applied covariate-adjusted linear regression models to examine associations between HFRs and outcomes, applying a false discovery rate correction of 0.1 for multiple comparisons. Several nominally significant associations were identified before correction, including a positive association between anti-DP and attention problems, negative associations between Dec602 and hyperactivity, and BB153 and hit reaction time variability. However, none remained significant after multiple comparison correction. Overall, we observed no significant associations between HFR concentrations in plasma or stool and ADHD-related traits or brain functional connectivity, suggesting that there is limited evidence for a link between them.