title: Manganese Exposure and Neurocognitive Outcomes in Rural School-Age Children: The Communities Actively Researching Exposure Study (Ohio, USA).
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Erin N
authors.initials: EN
authors.lastname: Haynes
authors.forename: Heidi
authors.initials: H
authors.lastname: Sucharew
authors.forename: Pierce
authors.initials: P
authors.lastname: Kuhnell
authors.forename: Jody
authors.initials: J
authors.lastname: Alden
authors.forename: Mary
authors.initials: M
authors.lastname: Barnas
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Parsons
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Aldous
authors.forename: Meredith L
authors.initials: ML
authors.lastname: Praamsma
authors.forename: Caroline
authors.initials: C
authors.lastname: Beidler
authors.forename: Kim N
authors.initials: KN
authors.lastname: Dietrich
mesh_terms: D002648:Child; D003071:Cognition / Q000187:drug effects*; D015331:Cohort Studies; D003367:Cotinine / Q000097:blood; D004781:Environmental Exposure; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity*; D005260:Female; D006197:Hair / Q000737:chemistry; D006801:Humans; D007854:Lead / Q000097:blood / Q000633:toxicity; D008297:Male; D008345:Manganese / Q000097:blood / Q000633:toxicity*; D009820:Ohio
chemical_list: D004785:Environmental Pollutants; D007854:Lead; D008345:Manganese; D003367:Cotinine