Exposure to Manganese in Drinking Water During Childhood and Association with Attention-Deficit Hyperactivity Disorder: A Nationwide Cohort Study
26 Pages Posted: 13 Apr 2019More...
Background: Attention-deficit hyperactivity disorder (ADHD) is a heritable mental disorder with little knowledge on environmental aetiology. Recent animal and epidemiological studies suggest that exposure to manganese (Mn) in drinking water may increase the risk of several neurodevelopmental endpoints. Earlier epidemiological studies on associations between Mn-exposure and problems with inattention, hyperactivity and impulsivity had small sample sizes, no longitudinal exposure assessment, and relied on questionnaire data on parent- or teacher-rated behavioural symptoms as the outcome (not diagnoses), shortcomings that we address here.
Methods: Accessing Danish national registers, we followed 643 401 children for ADHD and its subtypes between 1997 and 2016. We used data from 82 574 drinking water samples to model Mn-exposure during the first five years of life, with high temporal and spatial resolution. We estimated hazard ratios (HR), stratified by sex and adjusted for age, calendar year, and SES, using Cox proportional hazards models.
Findings: During follow-up (7·4 million person-years), 22 730 cohort members were diagnosed with ADHD. Females exposed to more than 100 µg/L during their first five years of life had an HRfemales,adjusted of 1·09 (95% CI 1·00-1·18) for ADHD, when compared to females exposed to <5 µg/L. No association with ADHD was found in males. Exposure to high levels of Mn (>100 µg/L ) was associated with the development of ADHD - Inattentive subtype in both sexes, when compared to exposure to <5 µg/L in same-sex individuals: HRfemales, adjusted 1·51 (1·18-1·93) and HRmales, adjusted 1·20 (1·01-1·42).
Interpretation: The association between Mn in drinking water and ADHD is driven by inattentive subtype and mainly in females, which supports previous findings on associations between Mn and cognitive development. Longitudinal exposure estimation with high resolution is crucial when assessing health outcomes of Mn exposure.
Funding: This study was supported by a grant from the Aarhus University Research Foundation.
Declaration of Interest: The authors declare they have no actual or potential competing financial interests.
Ethical Approval: The Danish Data Protection Agency and the Danish Health Data Authority approved this study.
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