TY - JOUR
T1 - Exposure to manganese in drinking water during childhood and association with attention-deficit hyperactivity disorder
T2 - A nationwide cohort study
AU - Schullehner, Jörg
AU - Thygesen, Malene
AU - Kristiansen, Søren Munch
AU - Hansen, Birgitte
AU - Pedersen, Carsten Bøcker
AU - Dalsgaard, Søren
N1 - Funding Information:
The authors thank engineer I.L. Breda from Skanderborg Forsyningsvirksomhed A/S for her valuable input on current research on manganese water treatment at the Danish waterworks. This study was funded by a grant from the Aarhus University Research Foundation (AUFF-E-2015-FLS-8-61). The research of S.D. is supported by grants from the Lundbeck Foundation (iPSYCH grant R102-A9118, R155-2014-1724, and R248-2017-2003), National Institutes of Health (R01, grant ES026993), Novo Nordisk Foundation (grant 22018), the European Commission (Horizon 2020, grant 667302), and Helsefonden (grant 19-8-0260).
Publisher Copyright:
© Public Health Services, US Dept of Health and Human Services. All rights reserved.
PY - 2020/9
Y1 - 2020/9
N2 - BACKGROUND: Manganese (Mn) in drinking water may increase the risk of several neurodevelopmental outcomes, including attention-deficit hyperactivity disorder (ADHD). Earlier epidemiological studies on associations between Mn exposure and ADHD-related outcomes had small sample sizes, lacked spatiotemporal exposure assessment, and relied on questionnaire data (not diagnoses)—shortcomings that we address here. OBJECTIVE: Our objective was to assess the association between exposure to Mn in drinking water during childhood and later development of ADHD. METHODS: In a nationwide population-based registry study in Denmark, we followed a cohort of 643,401 children born 1992–2007 for clinical diagnoses of ADHD. In subanalyses, we classified cases into ADHD-Inattentive and ADHD-Combined subtypes based on hierarchical categorization of International Classification of Diseases (ICD)-10 codes. We obtained Mn measurements from 82,574 drinking water samples to estimate longitudinal exposure during the first 5 y of life with high spatiotemporal resolution. We modeled exposure as both peak concentration and time-weighted average. We estimated sex-specific hazard ratios (HRs) in Cox proportional hazards models adjusted for age, birth year, socioeconomic status (SES), and urbanicity. RESULTS: We found that exposure to increasing levels of Mn in drinking water was associated with an increased risk of ADHD-Inattentive subtype, but not ADHD-Combined subtype. After adjusting for age, birth year, and SES, females exposed to high levels of Mn (i.e., >100 lg=L) at least once during their first 5 y of life had an HR for ADHD-Inattentive subtype of 1.51 [95% confidence interval (CI): 1.18, 1.93] and males of 1.20 (95% CI: 1.01, 1.42) when compared with same-sex individuals exposed to <5 lg=L. When modeling exposure as a time-weighted average, sex differences were no longer present. DISCUSSION: Mn in drinking water was associated with ADHD, specifically the ADHD-Inattentive subtype. Our results support earlier studies suggesting a need for a formal health-based drinking water guideline value for Mn. Future Mn-studies should examine ADHD subtype-specific associations and utilize direct subtype measurements rather than relying on ICD-10 codes alone. https://doi.org/10.1289/EHP6391.
AB - BACKGROUND: Manganese (Mn) in drinking water may increase the risk of several neurodevelopmental outcomes, including attention-deficit hyperactivity disorder (ADHD). Earlier epidemiological studies on associations between Mn exposure and ADHD-related outcomes had small sample sizes, lacked spatiotemporal exposure assessment, and relied on questionnaire data (not diagnoses)—shortcomings that we address here. OBJECTIVE: Our objective was to assess the association between exposure to Mn in drinking water during childhood and later development of ADHD. METHODS: In a nationwide population-based registry study in Denmark, we followed a cohort of 643,401 children born 1992–2007 for clinical diagnoses of ADHD. In subanalyses, we classified cases into ADHD-Inattentive and ADHD-Combined subtypes based on hierarchical categorization of International Classification of Diseases (ICD)-10 codes. We obtained Mn measurements from 82,574 drinking water samples to estimate longitudinal exposure during the first 5 y of life with high spatiotemporal resolution. We modeled exposure as both peak concentration and time-weighted average. We estimated sex-specific hazard ratios (HRs) in Cox proportional hazards models adjusted for age, birth year, socioeconomic status (SES), and urbanicity. RESULTS: We found that exposure to increasing levels of Mn in drinking water was associated with an increased risk of ADHD-Inattentive subtype, but not ADHD-Combined subtype. After adjusting for age, birth year, and SES, females exposed to high levels of Mn (i.e., >100 lg=L) at least once during their first 5 y of life had an HR for ADHD-Inattentive subtype of 1.51 [95% confidence interval (CI): 1.18, 1.93] and males of 1.20 (95% CI: 1.01, 1.42) when compared with same-sex individuals exposed to <5 lg=L. When modeling exposure as a time-weighted average, sex differences were no longer present. DISCUSSION: Mn in drinking water was associated with ADHD, specifically the ADHD-Inattentive subtype. Our results support earlier studies suggesting a need for a formal health-based drinking water guideline value for Mn. Future Mn-studies should examine ADHD subtype-specific associations and utilize direct subtype measurements rather than relying on ICD-10 codes alone. https://doi.org/10.1289/EHP6391.
UR - http://www.scopus.com/inward/record.url?scp=85091469813&partnerID=8YFLogxK
U2 - 10.1289/EHP6391
DO - 10.1289/EHP6391
M3 - Article
C2 - 32955354
AN - SCOPUS:85091469813
SN - 0091-6765
VL - 128
JO - Environmental Health Perspectives
JF - Environmental Health Perspectives
IS - 9
M1 - 097004
ER -