title: Associations of early childhood manganese and lead coexposure with neurodevelopment.
abstract: BACKGROUND
  Most toxicologic studies focus on a single agent, although this does not reflect real-world scenarios in which humans are exposed to multiple chemicals.
  
  
  OBJECTIVE
  We prospectively studied manganese-lead interactions in early childhood to examine whether manganese-lead coexposure is associated with neurodevelopmental deficiencies that are more severe than expected based on effects of exposure to each metal alone.
  
  
  METHODS
  Four hundred fifty-five children were enrolled at birth in an longitudinal cohort study in Mexico City, provided blood samples, and were followed until 36 months of age. We measured lead and manganese at 12 and 24 months and assessed neurodevelopment at 6-month intervals from 12 to 36 months of age using Bayley Scales of Infant Development-II.
  
  
  RESULTS
  Mean (± SD) blood concentrations at 12 and 24 months were, respectively, 24.7 ± 5.9 μg/L and 21.5 ± 7.4 μg/L for manganese and 5.1 ± 2.6 μg/dL and 5.0 ± 2.9 μg/dL for lead. Mixed-effects models, including Bayley scores at five time points, showed a significant interaction over time: highest manganese quintile × continuous lead; mental development score, β = -1.27 [95% confidence interval (CI): -2.18, -0.37]; psychomotor development score, β = -0.92 (95% CI: -1.76, -0.09). Slopes for the estimated 12-month lead effect on 18-month mental development and 24- through 36-month psychomotor development scores were steeper for children with high manganese than for children with midrange manganese levels.
  
  
  CONCLUSIONS
  We observed evidence of synergism between lead and manganese, whereby lead toxicity was increased among children with high manganese coexposure. Findings highlight the importance of understanding health effects of mixed exposures, particularly during potentially sensitive developmental stages such as early childhood.
authors: Department of Environmental Health, Harvard School of Public Health, 401 Park Dr., Boston, MA 02215, USA. bclaus@hsph.harvard.edu
authors: Birgit
authors: B
authors: Claus Henn
authors: Lourdes
authors: L
authors: Schnaas
authors: Adrienne S
authors: AS
authors: Ettinger
authors: Joel
authors: J
authors: Schwartz
authors: Héctor
authors: H
authors: Lamadrid-Figueroa
authors: Mauricio
authors: M
authors: Hernández-Avila
authors: Chitra
authors: C
authors: Amarasiriwardena
authors: Howard
authors: H
authors: Hu
authors: David C
authors: DC
authors: Bellinger
authors: Robert O
authors: RO
authors: Wright
authors: Martha María
authors: MM
authors: Téllez-Rojo
mesh_terms: D002657:Child Development / Q000187:drug effects*; D002675:Child, Preschool; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007854:Lead / Q000097:blood / Q000633:toxicity*; D008137:Longitudinal Studies; D008297:Male; D008345:Manganese / Q000097:blood / Q000633:toxicity*; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects*
chemical_list: D007854:Lead; D008345:Manganese