BACKGROUND: Children, especially those living near industry sites, are commonly exposed to multiple metals including lead and manganese. These metals are associated with adverse neurodevelopmental outcomes, with evidence of non-linear associations for essential metals. Metals target brain regions involved in cognition and motor function. However, there is a paucity of epidemiological studies focused on early-life exposure to metals, especially in association with less commonly studied neurodevelopmental domains like motor function.
OBJECTIVE: To characterize exposure to multiple metals in early life, estimate associations with neurodevelopmental outcomes in adolescence, and examine susceptibility factors including exposure timing, co-exposures, and biological sex.
METHODS: Research aims were addressed using data from the Assessing Children’s Environmental Exposures (ACHIEVE) study and the Public Health Impact of Metals Exposure (PHIME) study. The ACHIEVE study included 30 mother-child pairs from the town of Holliston, Massachusetts where naturally shed baby teeth were collected from children ages 5–13 years. In the first aim, we used multivariable linear mixed models to explore sociodemographic, dietary, and behavioral correlates of tooth metal concentrations for children in the ACHIEVE study (N=28). We estimated weekly prenatal and postnatal (up to one year of age) exposure to 12 metals. Tooth metal concentrations were quantified using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). For the second and third aims, we analyzed data from the PHIME study, comprised of 721 Italian adolescents living in proximity to steel production sites. Blood and hair samples were collected at the time of enrollment and analyzed for metals concentrations (manganese, lead, copper, and chromium) using ICP-MS. Teeth were collected for a subset of PHIME participants (N=195) and analyzed for manganese using LA-ICP-MS. A battery of neuropsychological assessments was administered to PHIME participants at enrollment by one of two trained neuropsychologists. In the second aim, we evaluated associations of prenatal, postnatal and childhood manganese levels in teeth with scores of adolescent verbal learning and memory, assessed using an Italian translation of the California Verbal Learning Test for Children (CVLT-C) (N=140). Associations were estimated using multivariable linear and logistic regression, generalized estimating equations and multiple informant models. In the third aim, we estimated associations of a metal mixture (lead, manganese, copper, and chromium) with multiple assessments of motor function (N=612). Statistical methods included generalized additive models, multivariable linear regression, quantile g-computation and Bayesian kernel machine regression. In the second and third aims, we also stratified analysis by sex to examine effect measure modification.
Results: In the first aim, we found that temporal trends of tooth metal levels differed by metals and correlates of tooth metal levels included biological sex and primary source of milk during infancy. In the second aim, we estimated manganese-cognition associations that differed by exposure time window: prenatal manganese and childhood manganese for boys was beneficial but postnatal manganese associations were null. In the third aim, we observed sex-specific associations between a metal mixture with motor function scores. The metal mixture was associated with improved motor function scores among females (driven by copper and chromium) whereas the metal mixture was associated with worse motor function scores among males (driven by manganese and copper).
CONCLUSION: The association between metal exposure in early life with neurodevelopment is dynamic and complex: associations between metals and neurodevelopment depend on exposure timing, biological sex, and co-exposures. This body of research can be used to inform future research by contributing to the understanding of metal neurotoxicity in critical windows of development and in relation to less studied neurodevelopmental domains, like motor function. / 2025-01-20T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/45493 |
| Date | 20 January 2023 |
| Creators | Friedman, Alexa |
| Contributors | Claus Henn, Birgit G. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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