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.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Neurological, Aging and Musculoskeletal Epidemiology (NAME)
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Kirshner, Annette G
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University of Michigan Ann Arbor
Public Health & Prev Medicine
Schools of Public Health
Ann Arbor
United States
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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; 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; 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
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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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