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

摘要 在世界范围内，数百万儿童暴露于有毒金属，包括铅（Pb）、砷（As）、镉（Cd）， 和锰（Mn），对它们的健康和发育具有重要影响。研究结果显示， 确定接触单一有毒金属与儿童神经行为缺陷之间的联系。然而，在这方面， 金属接触很少单独发生。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的影响，往往结果好坏参半。也有一些不足-- 多种金属暴露对儿童结局的长期影响的地位。因此，数据稀缺 和方法上的限制，使这一领域无法为保护 儿童和儿科实践。这项研究的长期目标是了解低水平暴露于 多种有毒金属影响儿童和青少年的神经行为结果， 金属对儿童结局的协同效应。这项研究的目的是确定如何 儿童暴露于多种金属会通过中间儿童影响特定的认知功能和行为- 胡德。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， 对一年级学生的研究。本研究的重点是As、Cd、Mn、Pb，因为这些元素存在于生物体内， 环境和从乌拉圭儿童身上收集的生物样本中的逻辑相关水平。的 中心假设是，在低暴露范围内，较高浓度的As、Cd、Mn和Pb将 随着时间的推移，单独与较差的认知和行为有关，共同接触这些金属将 对神经行为结果产生累加或倍增的负面影响。具体目标是 研究的目的是：1）描述砷，镉，锰和铅的长期暴露的趋势和变化，2）特征， 研究了体内金属负荷与特定认知功能缺陷的相关程度， 和3）描述金属与报告和观察到的问题相关的程度， IORS。研究人群将包括约760名儿童。该研究采用交错设计，需要：1）以下内容- 在以前的两项研究（2010-2013年）中被评估为一年级学生的儿童的低水平，以及2） 一年级入学和对其他儿童群体的后续行动。将采集头发和血液样本 每年进行一次，并在一、三、五年级对儿童的认知和行为进行评估。这种方法是创新的- 这是因为，与以往的研究相比，本研究采用了纵向研究方法来考察相互作用 在环境中以低水平存在的多种金属中，并采用特定的面向过程的齿轮， 与智商相反，智商是一种总结性的衡量标准。本研究具有重要的理论意义和现实意义。 与接触多种有毒金属相关的健康风险的沟通， 为预防或减轻暴露对发展的影响的方法做出贡献。

ABSTRACT 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 con- firm 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, 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 bio- logically 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) charac- terize 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 behav- iors. The study population will consist of ~760 children. The study has a staggered design, entailing: 1) the fol- low-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 innova- tive 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 cog- nitive outcomes as opposed to IQ, which is a summative measure. This research is significant in its contribu- tion 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.