Dataset Information

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

ABSTRACT: 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?g/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?g/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.

SUBMITTER: Schullehner J

PROVIDER: S-EPMC7505135 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Schullehner Jörg J Thygesen Malene M Kristiansen Søren Munch SM Hansen Birgitte B Pedersen Carsten Bøcker CB Dalsgaard Søren S

Environmental health perspectives 20200921 9

<h4>Background</h4>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.<h4>Objective</h4>Our objective was to assess the association between exposure to M ...[more]

PMID: 32955354

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Project description:ImportancePolysubstance use among pregnant women has increased because of the opioid epidemic and the increasing legalization of cannabis along with persistent tobacco and alcohol consumption. Previous research on prenatal substance use and the child's risk of attention-deficit/hyperactivity disorder (ADHD) has mostly focused on single-substance exposures; simultaneous examination of multiple substance use and assessment of their synergistic health consequences is needed.ObjectivesTo assess the consequences of the use of specific substances during pregnancy, investigate whether the interaction of multiple prenatal substance exposures is associated with increases in the risk of childhood ADHD, and estimate the aggregate burden of polysubstance exposure during gestation.Design, setting, and participantsThis cohort study analyzed data from the Boston Birth Cohort from 1998 to 2019. The sample of the present study comprised a multiethnic urban cohort of mother-child pairs who were predominantly low income. A total of 3138 children who were enrolled shortly after birth at Boston Medical Center were included and followed up from age 6 months to 21 years.ExposuresSubstance use during pregnancy was identified based on self-reported tobacco smoking, alcohol consumption, and use of cannabis, cocaine, or opioids in any trimester of pregnancy. Diagnostic codes for neonatal opioid withdrawal syndrome or neonatal abstinence syndrome from the International Classification of Diseases, Ninth Revision, and the International Classification of Diseases, Tenth Revision, were also used to identify opioid exposure during gestation.Main outcomes and measuresADHD diagnosis in the child's electronic medical record.ResultsAmong 3138 children (1583 boys [50.4%]; median age, 12 years [IQR, 9-14 years]; median follow-up, 10 years [IQR, 7-12 years]) in the final analytic sample, 486 (15.5%) had an ADHD diagnosis and 2652 (84.5%) were neurotypical. The median postnatal follow-up duration was 12 years (IQR, 9-14 years). Among mothers, 46 women (1.5%) self-identified as Asian (non-Pacific Islander), 701 (22.3%) as Hispanic, 1838 (58.6%) as non-Hispanic Black, 227 (7.2%) as non-Hispanic White, and 326 (10.4%) as other races and/or ethnicities (including American Indian or Indigenous, Cape Verdean, Pacific Islander, multiracial, other, or unknown). A total of 759 women (24.2%) reported the use of at least 1 substance during pregnancy, with tobacco being the most frequently reported (580 women [18.5%]). Cox proportional hazards models revealed that opioid exposure (60 children) had the highest adjusted hazard ratio (HR) for ADHD (2.19; 95% CI, 1.10-4.37). After including main statistical effects of all individual substances in an elastic net regression model, the HR of opioids was reduced to 1.60, and evidence of a statistical interaction between opioids and both cannabis and alcohol was found, producing 1.42 and 1.15 times higher risk of ADHD, respectively. The interaction between opioids and smoking was also associated with a higher risk of ADHD (HR, 1.17).Conclusions and relevanceThe findings of this study suggest that it is important to consider prenatal concurrent exposure to multiple substances and their possible interactions when counseling women regarding substance use during pregnancy, the future risk of ADHD for their children, and strategies for cessation and treatment programs.

Project description:BackgroundSome recent clinical studies have found that early childhood exposure to anesthesia is associated with increased risks of behavioral deficits and clinical diagnoses of attention deficit hyperactivity disorder (ADHD). While diagnoses in claims data may be subject to inaccuracies, pharmacy claims are highly accurate in reflecting medication use. This study examines the association between exposure to surgery and anesthesia and subsequent ADHD medication use.MethodsLongitudinal data for children enrolled in Texas and New York Medicaid from 1999 to 2010 were used. We assessed the association between a single exposure to anesthesia before age 5 years for 1 of 4 common pediatric surgical procedures (pyloromyotomy, inguinal hernia repair, circumcisions outside the perinatal period, and tonsillectomy and/or adenoidectomy) and persistent ADHD medication use (event defined as the initial ADHD medication prescription, and persistent use defined as filling 2 or more ≥30-day prescriptions between 6 months following surgery until censoring). Exposed children (n = 42,687) were matched on propensity score (ie, the probability of receiving surgery) estimated in logistic regression including sociodemographic and clinical covariates, to children without anesthesia exposure before age 5 years (n = 213,435). Cox proportional hazards models were used to evaluate the hazard ratio (HR) of ADHD medication use following exposure. Nonpsychotropic medications served as negative controls to determine if exposed children simply had higher overall medication use.ResultsChildren with a single exposure to surgery and anesthesia were 37% more likely than unexposed children to persistently use ADHD medication (HR, 1.37; 95% confidence interval [CI], 1.30-1.44). The estimated HRs for common nonpsychotropic medication use following a single anesthetic exposure were 1.06 (95% CI, 1.04-1.07) for amoxicillin, 1.10 (95% CI, 1.08-1.12) for azithromycin, and 1.08 (95% CI, 1.05-1.11) for diphenhydramine. In comparison, the risk of using other psychotropic medication to treat conditions besides ADHD was also significantly higher, with HRs of 1.37 (95% CI, 1.24-1.51) for sedative/anxiolytics, 1.40 (95% CI, 1.25-1.58) for antidepressants, 1.31 (95% CI, 1.20-1.44) for antipsychotics, and 1.24 (95% CI, 1.10-1.40) for mood stabilizers.ConclusionsMedicaid-enrolled children receiving anesthesia for a single common pediatric surgical procedure under age 5 years were 37% more likely to require subsequent persistent use of ADHD medications than unexposed children. Because the increased use of ADHD medication is disproportionately higher than that of nonpsychotropic medications, unmeasured confounding may not account for all of the increase in ADHD medication use. By evaluating Medicaid data, this study assesses children who may be particularly vulnerable to neurotoxic exposures.

Dataset Information

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

Publications

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

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