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Exposure to Manganese in Drinking Water During Childhood and Association with Attention-Deficit Hyperactivity Disorder: A Nationwide Cohort Study

26 Pages Posted: 13 Apr 2019

See all articles by Jörg  Schullehner

Jörg  Schullehner

Aarhus University - National Centre for Register-Based Research; Aarhus University - CIRRAU - Centre for Integrated Register-Based Research; Geological Survey of Denmark and Greenland

Malene Thygesen

Aarhus University - National Centre for Register-Based Research

Søren Munch Kristiansen

Aarhus University - Department of Geoscience

Birgitte Hansen

Geological Survey of Denmark and Greenland

Carsten Bøcker Pedersen

Aarhus University - National Centre for Register-Based Research

Søren Dalsgaard

Aarhus University - National Centre for Register-Based Research

More...

Abstract

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.

Suggested Citation

Schullehner, Jörg  and Thygesen, Malene and Kristiansen, Søren Munch and Hansen, Birgitte and Pedersen, Carsten Bøcker and Dalsgaard, Søren, Exposure to Manganese in Drinking Water During Childhood and Association with Attention-Deficit Hyperactivity Disorder: A Nationwide Cohort Study (April 10, 2019). Available at SSRN: https://ssrn.com/abstract=3369767 or http://dx.doi.org/10.2139/ssrn.3369767

Jörg  Schullehner (Contact Author)

Aarhus University - National Centre for Register-Based Research ( email )

8000 Århus C, 8210
Denmark

Aarhus University - CIRRAU - Centre for Integrated Register-Based Research ( email )

Aarhus
Denmark

Geological Survey of Denmark and Greenland ( email )

Aarhus
Denmark

Malene Thygesen

Aarhus University - National Centre for Register-Based Research

8000 Århus C, 8210
Denmark

Søren Munch Kristiansen

Aarhus University - Department of Geoscience

Aarhus
Denmark

Birgitte Hansen

Geological Survey of Denmark and Greenland

Aarhus
Denmark

Carsten Bøcker Pedersen

Aarhus University - National Centre for Register-Based Research

8000 Århus C, 8210
Denmark

Søren Dalsgaard

Aarhus University - National Centre for Register-Based Research

8000 Århus C, 8210
Denmark

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