Exposome of attention deficit hyperactivity disorder in Taiwanese children: exploring risks of endocrine-disrupting chemicals

Background: Attention-deficit hyperactivity disorder (ADHD) is diagnosed in ~7% of school-aged children. The role of endocrine-disrupting chemicals (EDC) and oxidative stress in ADHD etiology are not clear. Objective: Assessment of the associations between simultaneous exposure to multiple compounds and ADHD in children. Methods: The case-control study included 76 clinically diagnosed ADHD cases and 98 controls, aged 4–15 years old. Concentrations quartiles of urinary metabolites of acrylamide, acrolein, nonylphenol, phthalates, and organophosphate pesticides and biomarkers of oxidative stress were used to fit logistic regressions for each compound and weighted quantiles sum (WQS) regression for the mixture. Results: Positive dose-response relationships with ADHD were observed for 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) (odds ratio(OR)_Q4 = 3.73, 95%CI [1.32, 11.04], p_trend = 0.003), dimethyl phosphate (DMP) (OR_Q4 = 4.04, 95%CI [1.34, 12.94], p_trend = 0.014) and diethyl phosphate (OR_Q4 = 2.61, 95%CI = [0.93, 7.66], p_trend = 0.030), and for the mixture of compounds (OR_WQS = 3.82, 95%CI = [1.78, 8.19]) with the main contributions from HNE-MA (28.9%) and DMP (18.4%). Conclusions: The dose-response relationship suggests enhanced susceptibility to EDC burden in children even at lower levels, whereas the main risk is likely from organophosphate pesticides. HNE-MA is recommended as a sensitive biomarker of lipid peroxidation in the further elucidation of the oxidative stress role in ADHD etiology.