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

Abstract

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], ptrend = 0.003), dimethyl phosphate (DMP) (ORQ4 = 4.04, 95%CI [1.34, 12.94], ptrend = 0.014) and diethyl phosphate (ORQ4 = 2.61, 95%CI = [0.93, 7.66], ptrend = 0.030), and for the mixture of compounds (ORWQS = 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.

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Fig. 1: Correlation matrix of urinary metabolites and biomarkers (N = 174).
Fig. 2: Index weights from the weighted quantiles sum regression model.
Fig. 3: Predicted probability of attention-deficit hyperactivity disorder as a function of weighted quantiles sum index (WQS).

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Acknowledgements

We would like to express our gratitude to the little patients of Taipei City Hospital, their parents, the medical and laboratory personnel, who devoted their time, efforts, and goodwill to make this study happen.

Funding

Funding

This study was financially supported by the Ministry of Science and Technology of the Republic of China (MOST 105-2314-B-010-019-, MOST107-2314-B-010-051-MY2) and the Department of Health, Taipei City Government (10301-62-004).

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Correspondence to Mei-Lien Chen.

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Waits, A., Chang, CH., Yu, CJ. et al. Exposome of attention deficit hyperactivity disorder in Taiwanese children: exploring risks of endocrine-disrupting chemicals. J Expo Sci Environ Epidemiol 32, 169–176 (2022). https://doi.org/10.1038/s41370-021-00370-0

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