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Associations of Early Childhood Manganese and Lead Coexposure with Neurodevelopment

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This prospective cohort analysis measured manganese and lead in whole blood of Mexico City children at 12 and 24 months and followed neurodevelopment with the Bayley scales to 36 months. Among children in the highest quintile of 12-month blood manganese, lead was associated with steeper declines in mental and psychomotor scores than among children with midrange manganese. No interaction was seen with 24-month blood metals.

Key numbers

  • Blood manganese, arithmetic mean ± SD: 24.7 ± 5.9 µg/L at 12 months (range 15.3 to 73.9; n = 275) and 21.5 ± 7.4 µg/L at 24 months (range 5.1 to 93.5; n = 437) (Results, p. 127; Table 1).
  • Blood lead: 5.1 ± 2.6 µg/dL at 12 months and 5.0 ± 2.9 µg/dL at 24 months (Results, p. 127).
  • Highest manganese quintile at 12 months spanned 28.14 to 73.95 µg/L; lowest quintile 15.30 to 20.16 µg/L (Table 2 footnotes, p. 128).
  • Interaction, highest 12-month manganese quintile × continuous lead, repeated-measures models: mental development β = -1.27 (95% CI -2.18 to -0.37); psychomotor development β = -0.92 (95% CI -1.76 to -0.09) (Table 2, p. 128).
  • Limits of detection averaged 0.09 µg/dL for manganese and 0.04 µg/dL for lead; all samples were above them; recoveries 78 to 113% (Methods, p. 127).

Methods (brief)

Venous whole blood was analyzed by dynamic reaction cell ICP-MS at the Harvard trace metals laboratory. Neurodevelopment was assessed at 12, 18, 24, 30 and 36 months with the Spanish Bayley Scales of Infant Development II. Mixed-effects models adjusted for sex, gestational age, hemoglobin, maternal IQ and maternal education. An earlier analysis of this cohort found an inverted U-shaped association of manganese with 12-month mental scores, which motivated the quintile approach.

Evidence fitness

The study supports reporting of blood manganese levels in young urban Mexican children and evidence that high manganese may increase lead’s neurodevelopmental toxicity in early childhood. It does not identify manganese sources and cannot set a threshold for dietary or water intake.

Limitations

Blood samples were convenience samples archived from a parent study, so 12-month data are fewer than 24-month data. Blood manganese is a short-term, homeostatically regulated marker. The interaction was not seen for 24-month metals, and some sensitivity analyses gave weaker estimates.

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