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Uncovering neurodevelopmental windows of susceptibility to manganese exposure using dentine microspatial analyses.

ABSTRACT: BACKGROUND:Associations between manganese (Mn) and neurodevelopment may depend on dose and exposure timing, but most studies cannot measure exposure variability over time well. OBJECTIVE:We apply temporally informative tooth-matrix biomarkers to uncover windows of susceptibility in early life when Mn is associated with visual motor ability in childhood. We also explore effect modification by lead (Pb) and child sex. METHODS:Participants were drawn from the ELEMENT (Early Life Exposures in MExico and NeuroToxicology) longitudinal birth cohort studies. We reconstructed dose and timing of prenatal and early postnatal Mn and Pb exposures for 138 children by analyzing deciduous teeth using laser ablation-inductively coupled plasma-mass spectrometry. Neurodevelopment was assessed between 6 and 16 years of age using the Wide Range Assessment of Visual Motor Abilities (WRAVMA). Mn associations with total WRAVMA scores and subscales were estimated with multivariable generalized additive mixed models. We examined Mn interactions with Pb and child sex in stratified models. RESULTS:Levels of dentine Mn were highest in the second trimester and declined steeply over the prenatal period, with a slower rate of decline after birth. Mn was positively associated with visual spatial and total WRAVMA scores in the second trimester, among children with lower (< median) tooth Pb levels: one standard deviation (SD) increase in ln-transformed dentine Mn at 150 days before birth was associated with a 0.15 [95% CI: 0.04, 0.26] SD increase in total score. This positive association was not observed at high Pb levels. In contrast to the prenatal period, significant negative associations were found in the postnatal period from ~ 6 to 12 months of age, among boys only: one SD increase in ln-transformed dentine Mn was associated with a 0.11 [95% CI: - 0.001, - 0.22] to 0.16 [95% CI: - 0.04, - 0.28] SD decrease in visual spatial score. CONCLUSIONS:Using tooth-matrix biomarkers with fine scale temporal profiles of exposure, we found discrete developmental windows in which Mn was associated with visual-spatial abilities. Our results suggest that Mn associations are driven in large part by exposure timing, with beneficial effects found for prenatal levels and toxic effects found for postnatal levels.

SUBMITTER: Claus Henn B

PROVIDER: S-EPMC5965684 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Uncovering neurodevelopmental windows of susceptibility to manganese exposure using dentine microspatial analyses.

Claus Henn Birgit B Austin Christine C Coull Brent A BA Schnaas Lourdes L Gennings Chris C Horton Megan K MK Hernández-Ávila Mauricio M Hu Howard H Téllez-Rojo Martha Maria MM Wright Robert O RO Arora Manish M

Environmental research 20180201

<h4>Background</h4>Associations between manganese (Mn) and neurodevelopment may depend on dose and exposure timing, but most studies cannot measure exposure variability over time well.<h4>Objective</h4>We apply temporally informative tooth-matrix biomarkers to uncover windows of susceptibility in early life when Mn is associated with visual motor ability in childhood. We also explore effect modification by lead (Pb) and child sex.<h4>Methods</h4>Participants were drawn from the ELEMENT (Early Li ...[more]

PMID: 29247915

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Project description:BackgroundPrenatal overexposure to manganese (Mn), an essential micronutrient, is related to impaired fetal growth and development. Fetuses appear to be highly sensitive to Mn during short periods of gestation. However, little is known about the critical windows of susceptibility to Mn for humans.ObjectivesOur objective was to estimate trimester-specific associations of exposure to Mn with size at birth.MethodsUrine samples of 3,022 women were collected repeatedly in the first, second, and third trimesters in Wuhan, China. Urinary concentrations of Mn and other toxic metals were measured using an inductively coupled plasma mass spectrometry. Trimester-specific associations of specific gravity–adjusted urinary Mn concentrations with birth weight, birth length, and ponderal index were estimated using multivariable linear regressions with generalized estimating equations. Linear mixed models were applied to evaluate the windows of susceptibility to Mn exposure by comparing the pattern of Mn exposure among newborns with restricted size at birth to those without.ResultsWhen compared with the third quintile of urinary Mn concentrations, both higher and lower quintiles of urinary Mn concentrations in the second and third trimesters were related to reduced birth weight, birth length, and ponderal index. But the observed associations for higher quintiles were stronger and more likely to be statistically significant [e.g., for women who were in the fifth quintile of Mn concentration in the third trimester, the reduction in birth weight was [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) g and in birth length was [Formula: see text] (95% CI: [Formula: see text], 0.00) cm]. Moreover, newborns with restricted size at birth, compared with those without, had higher levels of Mn exposure in the second and third trimesters.ConclusionsThis prospective prenatal cohort study revealed an association of exposure to Mn during pregnancy, especially late pregnancy, with restricted size at birth. Replications are needed. https://doi.org/10.1289/EHP3423.

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Uncovering neurodevelopmental windows of susceptibility to manganese exposure using dentine microspatial analyses.

Publications

Uncovering neurodevelopmental windows of susceptibility to manganese exposure using dentine microspatial analyses.

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