Halogenated flame retardants, thyroid function biomarkers, attention-deficit/hyperactivity disorder-related traits and neurodevelopment in children: Recent evidence from a Canadian prospective birth cohort study.

Halogenated flame retardants (HFRs) may disrupt thyroid hormone homeostasis, potentially affecting neurodevelopment in children. However, studies integrating multi-matrix HFR exposure assessment, thyroid function biomarkers, and multimodal neurodevelopmental outcomes in children remain limited. We examined associations of HFR exposures with thyroid function biomarker levels and, in turn, neurodevelopmental outcomes in children aged 8-12 years and evaluated thyroid function biomarkers as potential mediators. We utilized cross-sectional data within the prospective GESTation and Environment (GESTE) birth cohort in Canada. Among 167 children (57.5% female) with plasma HFRs and thyroid function biomarker data, 111 also provided stool samples, and 97-106 completed various attention-deficit/hyperactivity disorder-related trait scales, cognitive tests, and resting-state functional MRI. Higher plasma 2,2',4,4',5,5'-Hexabromodiphenyl ether (BDE-153) was associated with lower thyroid-stimulating hormone (TSH) (β = -0.20; 95% CI, -0.37 to -0.03), whereas higher stool 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) was associated with higher TSH (β = 0.14; 95% CI, 0.02 to 0.25). Higher TSH level was associated with lower block design score (β = -0.64; 95% CI, -1.17 to -0.11) and default mode network functional connectivity (β = -0.03; 95% CI, -0.05 to -0.01). Mediation analysis suggested an indirect effect of TSH in the association between stool BDE-47 and block design score (β = -0.14; 95% CI, -0.37 to -0.01). However, none of these associations above remained statistically significant after controlling for the false discovery rate. Despite the potential relationships between HFR exposures and TSH alterations that are linked to neurodevelopmental outcomes in school-aged children, the inconsistent results of HFRs from various studies suggest further evidence is needed to reveal the complex relationship.