Recent studies using national data have reported that developmental disabilities are prevalent (as high as 1 in every 6 children) and on the rise in the US and elsewhere. While the cause(s) of these trends are unknown, there is concern for the potential role of exposures to environmental neurotoxicants. There is growing animal evidence that agents to which many or most people are exposed at varying levels, including contemporary-use pesticides, heavy metals, and secondhand tobacco smoke (STS), are neurotoxic. With the exception of lead, human studies of these agents in relation to neurodevelopment are lacking, both alone and together as mixtures. In many settings elevated exposure to these agents may be accompanied by nutritional deficiencies, with iron deficiency (ID) being the most common. This may result in greater neurotoxicity by acting through similar mechanistic pathways or increasing susceptibility to exposure. Pregnancy and infancy are the periods of greatest concern due to vulnerability of the developing brain. The proposed study aims to: 1) Investigate the association between neurodevelopment and early life exposure to pesticides, metals (manganese and lead), and STS individually and in combination (i.e., additive and multiplicative effects);2) Test for interactions between these agents and ID on neurodevelopmental outcomes;and 3) Determine whether iron supplementation in pregnancy and/or in infancy ameliorates adverse impacts of environmental exposures on neurodevelopment outcome. The study will leverage two large ongoing NIH-supported studies of ID and neurodevelopment (n ~ 2500) taking place in rural China where elevated exposures, as well as widespread ID, have been documented. The study will utilize state-of-the-art approaches to assess exposures and outcomes. Detailed measures of sensory, motor, cognitive, affective-social and regulatory functions at birth/6 weeks, 9 months, and 18 months of age are collected in the ongoing studies. Exposure biomarkers will be measured in urine and blood samples from multiple time points in early development, including sensitive new methods to quantify >45 pesticides in cord blood. Expected outcomes of this study are to provide new and much needed information on the impacts of environmental exposures on neurodevelopment and prioritization of exposure risks, the specific processes and sensitive exposure windows involved the simultaneous effects of multiple exposures and ID on these endpoints, and evidence for potential interventions to lessen these effects through exposure reduction or iron supplementation. The study will likely have a significant impact on public health policy given widespread exposure to these agents worldwide, the global prevalence of ID, and increasing evidence that many environmental exposures contribute to poorer neurodevelopmental outcomes.

Public Health Relevance

Using innovative approaches to assess the risk of environmental exposures on child neurodevelopment, this study will have a significant impact on public health given widespread exposure to pesticides, heavy metals and STS worldwide, the global prevalence of iron deficiency, and concerns that environmental influences are contributing to the high and increasing rates of neurodevelopmental disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES021465-03
Application #
8651492
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Kirshner, Annette G
Project Start
2012-08-01
Project End
2017-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
3
Fiscal Year
2014
Total Cost
$625,267
Indirect Cost
$192,897
Name
University of Michigan Ann Arbor
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Silver, Monica K; Arain, Aubrey L; Shao, Jie et al. (2018) Distribution and predictors of 20 toxic and essential metals in the umbilical cord blood of Chinese newborns. Chemosphere 210:1167-1175
Silver, Monica K; Shao, Jie; Ji, Chai et al. (2018) Prenatal organophosphate insecticide exposure and infant sensory function. Int J Hyg Environ Health 221:469-478
Silver, Monica K; Shao, Jie; Zhu, Binquan et al. (2017) Prenatal naled and chlorpyrifos exposure is associated with deficits in infant motor function in a cohort of Chinese infants. Environ Int 106:248-256
Lou, J; Mai, X; Lozoff, B et al. (2016) Prenatal Iron Deficiency and Auditory Brainstem Responses at 3 and 10 Months: A Pilot Study. Hong Kong J Paediatr 20:71-79
Watkins, Deborah J; Fortenberry, Gamola Z; Sánchez, Brisa N et al. (2016) Urinary 3-phenoxybenzoic acid (3-PBA) levels among pregnant women in Mexico City: Distribution and relationships with child neurodevelopment. Environ Res 147:307-13
Silver, Monica K; Shao, Jie; Chen, Minjian et al. (2016) Distribution and Predictors of Pesticides in the Umbilical Cord Blood of Chinese Newborns. Int J Environ Res Public Health 13:
Jones, A D; Zhao, G; Jiang, Y-P et al. (2016) Maternal obesity during pregnancy is negatively associated with maternal and neonatal iron status. Eur J Clin Nutr 70:918-24
Silver, Monica K; Li, Xiaoqing; Liu, Yuhe et al. (2016) Low-level prenatal lead exposure and infant sensory function. Environ Health 15:65
Sturza, Julie; Silver, Monica K; Xu, Lin et al. (2016) Prenatal exposure to multiple pesticides is associated with auditory brainstem response at 9months in a cohort study of Chinese infants. Environ Int 92-93:478-85
Geng, Fengji; Mai, Xiaoqin; Zhan, Jianying et al. (2015) Impact of Fetal-Neonatal Iron Deficiency on Recognition Memory at 2 Months of Age. J Pediatr 167:1226-32

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