title: Prenatal and postnatal manganese teeth levels and neurodevelopment at 7, 9, and 10.5 years in the CHAMACOS cohort.
abstract: BACKGROUND
  Numerous cross-sectional studies of school-age children have observed that exposure to manganese (Mn) adversely affects neurodevelopment. However, few prospective studies have looked at the effects of both prenatal and postnatal Mn exposure on child neurodevelopment.
  
  
  METHODS
  We measured Mn levels in prenatal and early postnatal dentine of shed teeth and examined their association with behavior, cognition, memory, and motor functioning in 248 children aged 7, 9, and/or 10.5 years living near agricultural fields treated with Mn-containing fungicides in California. We used generalized linear models and generalized additive models to test for linear and nonlinear associations, and generalized estimating equation models to assess longitudinal effects.
  
  
  RESULTS
  We observed that higher prenatal and early postnatal Mn levels in dentine of deciduous teeth were adversely associated with behavioral outcomes, namely internalizing, externalizing, and hyperactivity problems, in boys and girls at 7 and 10.5 years. In contrast, higher Mn levels in prenatal and postnatal dentine were associated with better memory abilities at ages 9 and 10.5, and better cognitive and motor outcomes at ages 7 and 10.5 years, among boys only. Higher prenatal dentine Mn levels were also associated with poorer visuospatial memory outcomes at 9 years and worse cognitive scores at 7 and 10.5 years in children with higher prenatal lead levels (≥0.8 μg/dL). All these associations were linear and were consistent with findings from longitudinal analyses.
  
  
  CONCLUSIONS
  We observed that higher prenatal and early postnatal Mn levels measured in dentine of deciduous teeth, a novel biomarker that provides reliable information on the developmental timing of exposures to Mn, were associated with poorer behavioral outcomes in school-age boys and girls and better motor function, memory, and/or cognitive abilities in school-age boys. Additional research is needed to understand the inconsistencies in the neurodevelopmental findings across studies and the degree to which differences may be associated with different Mn exposure pathways and biomarkers.
authors.affiliation: Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, Berkeley, CA, USA; Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional, Heredia, Costa Rica.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Mora
authors.affiliation: Lautenberg Environmental Health Sciences Laboratory, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Arora
authors.affiliation: Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, Berkeley, CA, USA.
authors.forename: Kim G
authors.initials: KG
authors.lastname: Harley
authors.affiliation: Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, Berkeley, CA, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kogut
authors.affiliation: Clinica de Salud del Valle de Salinas, CA, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Parra
authors.affiliation: Division of Environmental Health, National Institute of Public Health, Mexico City, Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Hernández-Bonilla
authors.affiliation: Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, Berkeley, CA, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gunier
authors.affiliation: Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, Berkeley, CA, USA.
authors.forename: Asa
authors.initials: A
authors.lastname: Bradman
authors.affiliation: Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA, USA.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Smith
authors.affiliation: Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, Berkeley, CA, USA. Electronic address: eskenazi@berkeley.edu.
authors.forename: Brenda
authors.initials: B
authors.lastname: Eskenazi
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000032:analysis; D002140:California; D002648:Child; D002652:Child Behavior / Q000187:drug effects*; D002657:Child Development / Q000187:drug effects*; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects; D015331:Cohort Studies; D003804:Dentin / Q000737:chemistry; D004785:Environmental Pollutants / Q000032:analysis* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008345:Manganese / Q000032:analysis* / Q000493:pharmacokinetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology / Q000378:metabolism*; D014094:Tooth, Deciduous / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D008345:Manganese
keywords: California; Children; Manganese; Neurodevelopment; Teeth