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Background: Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance., Objectives: This study investigated the associations between childhood and adolescent Mn biomarkers and adolescent postural balance in participants from the longitudinal Marietta Communities Actively Researching Exposures Study (CARES) cohort., Methods: Participants were recruited into CARES when they were 7-9 y old, and reenrolled at 13-18 years of age. At both time points, participants provided samples of blood, hair, and toenails that were analyzed for blood Mn and lead (Pb), serum cotinine, hair Mn, and toenail Mn. In adolescence, participants completed a postural balance assessment. Greater sway indicates postural instability (harmful effect), whereas lesser sway indicates postural stability (beneficial effect). Multivariable linear regression models were conducted to investigate the associations between childhood and adolescent Mn biomarkers and adolescent postural balance adjusted for age, sex, height-weight ratio, parent/caregiver intelligence quotient, socioeconomic status, blood Pb, and serum cotinine., Results: CARES participants who completed the adolescent postural balance assessment ( n = 123 ) were 98% White and 54% female and had a mean age of 16 y (range: 13-18 y). In both childhood and adolescence, higher Mn biomarker concentrations were significantly associated with greater adolescent sway measures. Supplemental analyses revealed sex-specific associations; higher childhood Mn biomarker concentrations were significantly associated with greater sway in females compared with males., Discussion: This study found childhood and adolescent Mn biomarkers were associated with subclinical neuromotor effects in adolescence. This study demonstrates postural balance as a sensitive measure to assess the association between Mn biomarkers and neuromotor function. https://doi.org/10.1289/EHP13381.

Exposure to metal mixtures may lead to health impacts greater than the effects associated with singular exposures. Two common childhood environmental exposures, manganese (Mn) and lead (Pb), are associated with similar adverse neurodevelopmental effects; however, the effects surrounding concurrent exposure to both metals remain unclear. We study the impact of joint exposure to Mn and Pb on cognitive performance in school-aged children participating in the Communities Actively Researching Exposure Study (CARES) based in East Liverpool, Ohio. Blood Pb levels were measured for each child (geometric mean (GM) = 1.13 μg/dL, range 0.30 μg/dL - 6.64 μg/dL). Mn was measured in participant blood, hair, and toenails with GMs of 10.1 μg/L, 360 ng/g, 0.974 μg/g, respectively. Trained team members administered the Wechsler Intelligence Scale for Children-IV (WISC-IV) to assess intelligence quotient (IQ). The WISC-IV provides scores for Full Scale IQ, Perceptual Reasoning, Processing Speed, Working Memory, and Verbal Comprehension. Interactions between blood Pb and all Mn biomarkers were tested in linear models adjusted for child sex, household income, and serum cotinine. Separate regression models were run for each of the Mn biomarkers. The cohort was comprised of 106 children with a mean age of 8.4 years. Interactions between blood Pb and hair Mn were significant (p < 0.05) for four out of the five IQ domains. The effect of blood Pb on IQ was more pronounced at higher levels of hair and toenail Mn. No significant associations were observed when characterizing the main effect of Mn using blood. Uncovering the health impacts associated with exposure mixtures is critical to understanding the impact of real-life conditions. Our findings suggest that joint exposure to Mn and Pb may produce heightened neurocognitive impacts even at blood Pb levels below the CDC reference concentration of 5 μg/dL., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: East Liverpool, Ohio, the site of a hazardous waste incinerator and a manganese (Mn) processor, has had air Mn concentrations exceeding United States Environmental Protection Agency reference levels for over a decade. Save Our County, Inc., a community organization, was formed to address community environmental health concerns related to local industry. Researchers from the University of Cincinnati partnered with Save Our County to determine if air Mn had an impact on the neurocognitive function of children in the community., Methods: Children 7-9 years of age from East Liverpool and its surrounding communities, were enrolled (N=106) in the Communities Actively Researching Exposure Study from between March 2013-June 2014. Blood and hair were analyzed for Mn and lead, and serum was analyzed for cotinine. We used linear regression to assess associations between biological measures and IQ subscale scores., Results: Geometric mean blood lead (n=67), blood Mn (n=66), hair Mn (n=98), and serum cotinine (n=69) concentrations were 1.13±1.96μg/dL, 10.06±1.30μg/L, and 360.22±2.17ng/g, 0.76±6.12μg/L respectively. After adjusting for potential confounders, hair Mn was negatively associated with Full Scale IQ., Conclusions: Hair Mn was negatively associated with child IQ scores. Community partners were instrumental in the conception and implementation of this study., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Manganese (Mn) is both an essential micronutrient and potential neurotoxicant. This dual role underlies a growing body of literature demonstrating that Mn exhibits a biphasic dose-response relationship with neurocognitive outcomes. We reviewed recent epidemiologic studies from 2007 to 2016 that investigated the relationship between Mn exposure and cognitive outcomes across the lifespan: early life, school-aged children, and adulthood. In total, 27 research articles were included in this review: 12 pediatric and 15 adult studies (10 occupational and five environmental exposures). The majority of these studies provided evidence of the negative effects of Mn exposure on cognition. The pediatric literature provides evidence that both high and low levels of Mn are negatively associated with intellectual development. Future Mn research should include examination of non-linear relationships and multiple neurotoxicants across the lifespan and particularly during critical developmental windows.

Federal funding agencies increasingly support stakeholder participation in environmental health studies, and yet there is very little published research on engagement of community members in the development of data disclosure (DD) strategies. The Ohio Environmental Protection Agency reported airborne manganese (Mn) concentrations in East Liverpool, Ohio, 30 times higher than the reference concentration, which led to an academic–community research partnership to address community concern about Mn exposure, particularly among children. Children and their families were recruited to participate in a pilot study. Samples of blood and hair were collected from the children and analyzed for metals. DD mechanisms were developed using an iterative approach between community and academic partners. Individual DD letters were mailed to each participating family, and a community meeting was held. A post-meeting survey was administered to gauge community perception of the DD strategies. The purpose of this article is to demonstrate the effectiveness of engaging community partners in the conduct of environmental health research and in the development of DD strategies for individuals and the community at large. Scientists should include community partners in the development of DD strategies to enhance translation of the research findings and support the right of study participants to know their individual results.

Background: Manganese (Mn) plays a vital role in brain growth and development, yet excessive exposure can result in neurotoxicity. Marietta, Ohio, is home to the nation's longest-operating ferromanganese refinery, and community concern about exposure led to the development of the research study., Objectives: Our overall goal was to address the community's primary research question: "Does Mn affect cognitive development of children?" We evaluated the relationships between Mn exposure as measured by blood and hair Mn, along with other neurotoxicants including blood lead (Pb) and serum cotinine, and child cognition., Methods: Children 7-9 years of age were enrolled (n = 404) in the Communities Actively Researching Exposure Study (CARES) from Marietta and Cambridge, Ohio, and their surrounding communities from October 2008 through March 2013. Blood and hair were analyzed for Mn and Pb, and serum was analyzed for cotinine. We used penalized splines to assess potential nonlinear associations between biological measures and IQ subscale scores, followed by multivariable regression models with categorical variables based on quartiles of the distribution for biological measures with nonlinear associations and continuous variables for biological measures with linear associations., Results: Geometric mean blood (n = 327) and hair Mn (n = 370) concentrations were 9.67 ± 1.27 μg/L and 416.51 ± 2.44 ng/g, respectively. After adjusting for potential confounders, both low and high blood and hair Mn concentrations were associated with lower Full Scale IQ and subscale scores, with significant negative associations between the highest quartile and middle two quartiles of blood Mn (β -3.51; 95% CI: -6.64, -0.38) and hair Mn (β -3.66; 95% CI: -6.9, -0.43%) and Full Scale IQ., Conclusions: Both low and high Mn concentrations in blood and hair were negatively associated with child IQ scores. Serum cotinine was negatively associated with child cognitive function.

Airborne manganese (Mn) exposure can result in neurotoxicity and postural instability in occupationally exposed workers, yet few studies have explored the association ambient exposure to Mn in children and postural stability. The goal of this study was to determine the association between Mn and lead (Pb) exposure, as measured by blood Pb, blood and hair Mn and time weighted distance (TWD) from a ferromanganese refinery, and postural stability in children. A subset of children ages 7-9 years enrolled in the Marietta Community Actively Researching Exposure Study (CARES) were invited to participate. Postural balance was conducted on 55 children residing in Marietta, Ohio and the surrounding area. Samples of blood were collected and analyzed for Mn and Pb, and samples of hair were analyzed for Mn. Neuromotor performance was assessed using postural balance testing with a computer force platform system. Pearson correlations were calculated to identify key covariates. Associations between postural balance testing conditions and Mn and Pb exposure were estimated with linear regression analyses adjusting for gender, age, parent IQ, and parent age. Mean blood Mn was 10 μg/L (SEM=0.36), mean blood Pb was 0.85 μg/dL (SEM=0.05), and mean hair Mn was 0.76 μg/g (SEM=0.16). Mean residential distance from the refinery was 11.5 km (SEM=0.46). All three measures of Mn exposure were significantly associated with poor postural balance. In addition, low-level blood Pb was also negatively associated with balance outcomes. We conclude that Mn exposure and low-level blood Pb are significantly associated with poor postural balance., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Abstract: Antisocial behavior is a product of multiple interacting sociohereditary variables, yet there is increasing evidence that metal exposure, particularly, manganese and lead, play a role in its epigenesis. Other metals, such as arsenic, cadmium, chromium, and mercury, and exposure to traffic-related air pollution, such as fine particulate matter (≤2.5μm) have been associated with neurological deficits, yet largely unexplored with respect to their relationship with delinquent behavior. The purpose of this study is to evaluate the ecological relationship between county-wide reported airborne emissions of air metals, particulate matter, and youth adjudicated for criminal activity. Metal exposure data were collected from the Environmental Protection Agency AirData. Population statistics were obtained from the United States Census 2000 and adjudication data was obtained from the Courts of Common Pleases from each Ohio County. Simple correlations were calculated with the percentage of adjudications, all covariates, and estimated metal air emissions. Separate negative binomial regression models for each pollutant were used to provide an estimated risk ratio of pollutant emissions on the risk of adjudication for all Ohio counties adjusting for urban–rural residence, percentage of African Americans, median family income, percentage of family below poverty, percentage of high school graduation in 25 years and older populations, and population density. Metal emissions and PM in 1999 were all correlated with adjudication rate (2003–2005 average). Metal emissions were associated with slightly higher risk of adjudication, with about 3–4% increased risk per natural log unit of metal emission except chromium. The associations achieved statistical significance for manganese and mercury. The particulate matter ≤2.5 and ≤10μm emissions had a higher risk estimate, with 12% and 19% increase per natural log unit emission, respectively, and also achieved statistical significance. In summary, airborne exposure to manganese, mercury, and particulate matter are associated with increased risk of adjudication. Causality cannot be proven in observational studies such as this one, but the association warrants further examination in other research studies. Comprehensive epidemiologic investigations of metal exposure in pediatric populations should include social health outcomes, including measures of delinquent or criminal activity. Furthermore, the influence of metals on the neurotoxic pathway leading to delinquent activity should be further explored. [Copyright &y& Elsevier]