Low-level Exposure to Multiple Metals: Effects on Cognition and Behavior

描述（由申请人提供）：全世界有数百万儿童暴露于有毒金属，包括铅（Pb）、砷（As）、镉（Cd）和锰（Mn），对他们的健康和发育产生重要影响。研究结果证实了接触单一有毒金属与儿童神经行为缺陷之间的联系。然而，金属暴露很少单独发生。然而，迄今为止，很少有研究探讨了有毒金属对认知缺陷或行为问题之间的相互作用，结果往往好坏参半。也很少了解多种金属暴露对儿童结局的长期影响。因此，数据的稀缺和方法的局限性使这一领域无法为保护儿童和儿科实践提出合理的建议。这项研究的长期目标是了解低水平暴露于多种有毒金属如何影响儿童和青少年的神经行为结果，确定金属对儿童结果的潜在协同效应。这项研究的目的是确定儿童暴露于多种金属如何影响特定的认知功能和行为，通过中间的儿童期。拟议的研究是一项纵向队列研究，将在乌拉圭蒙得维的亚进行，并建立在以前对一年级儿童的研究基础上。这项研究的重点是砷，镉，锰，铅，因为这些发生在生物相关水平的环境和生物样本收集的乌拉圭儿童。中心假设是，在低范围内的曝光，高浓度的砷，镉，锰和铅将单独与较差的认知和行为随着时间的推移，以及共同暴露于这些金属将产生累加或乘法的负面影响神经行为的结果。本研究的具体目的是：1）描述长期暴露于As，Cd，Mn和Pb的趋势和变异性，2）表征身体金属负荷与特定认知功能缺陷相关的程度，3）表征金属与报告和观察到的问题行为相关的程度。研究人群将包括约760名儿童。该研究采用交错设计，包括：1）在之前的2项研究（2010-2013年）中被评估为一年级学生的儿童的随访，以及2）在一年级入组并随访额外的儿童队列。每年收集头发和血液样本，并在一年级、三年级和五年级评估儿童的认知和行为。这种方法是创新的，因为与以前的研究相比，采用纵向方法来研究环境中低水平的多种金属之间的相互作用，并采用特定的过程导向的认知结果，而不是智商，这是一种总结性的措施。这项研究是重要的，它的贡献与接触多种有毒金属的健康风险的沟通，并在其潜在的贡献，将防止或减轻暴露的发展后果的方法。

DESCRIPTION (provided by applicant): Worldwide, millions of children are exposed to toxic metals, including lead (Pb), arsenic (As), cadmium (Cd), and manganese (Mn), with important consequences for their health and development. Research findings confirm the association between exposure to single toxic metals and neurobehavioral deficits in children. However, metal exposures rarely occur in isolation. Nevertheless, few studies to date have examined interactions among toxic metals on cognitive deficits or behavioral problems, often with mixed results. There is also little under- standing of the long-term consequences of multiple metal exposures on child outcomes. Thus, the scarcity of data and methodological limitations have kept this field from making sound recommendations for the protection of children and pediatric practice. The long-term goal of this research is to understand how low-level exposure to multiple toxic metals affects neurobehavioral outcomes across childhood and adolescence, identifying potential synergistic effects of metals on children's outcomes. The objective of the proposed study is to determine how children's exposure to multiple metals affects specific cognitive functions and behavior through middle child- hood. The proposed study is a longitudinal cohort study that will take place in Montevideo, Uruguay and builds on previous research in 1st grade children. The study focuses on As, Cd, Mn, Pb because these occur at biologically relevant levels in the environment and biological samples collected from the Uruguayan children. The central hypothesis is that within low range of exposures, higher concentrations of As, Cd, Mn and Pb will be individually associated with poorer cognition and behavior over time, and that co-exposure to these metals will produce additive or multiplicative negative effects on neurobehavioral outcomes. The specific aims of this study are to: 1) describe the trends and variability of the long-term exposure to As, Cd, Mn and Pb, 2) characterize the extent to which body burden of the metals is associated with deficits in specific cognitive functions, and 3) characterize the extent to which the metals are associated with reported and observed problem behaviors. The study population will consist of ~760 children. The study has a staggered design, entailing: 1) the follow-up of children who had been evaluated as 1st-graders in 2 previous studies (years 2010-2013), and 2) the enrollment in 1st grade and follow-up of additional cohorts of children. Hair and blood samples will be collected yearly, and children's cognition and behavior will be evaluated in 1st, 3rd and 5th grade. This approach is innovative because, in contrast to previous studies, in employs a longitudinal approach to examine interactions among multiple metals that occur at low levels in the environment, and employs specific process-oriented cognitive outcomes as opposed to IQ, which is a summative measure. This research is significant in its contribution to the communication of health risks associated with exposure to multiple toxic metals, and in its potential contribution to approaches that will prevent or alleviate the developmental consequences of exposure.