Understanding Risk Gradients from Environment on Native American Child Health Trajectories: Toxicants, Immunomodulation, Metabolic syndromes, & Metals Exposure

总结 紧急美洲原住民ECHO队列将建立在活跃的纳瓦霍出生队列研究（NBCS）的基础上， 将随访期延长到目前的12个月方案之外，并增加两个额外的部落， 夏延河和奥格拉拉苏族部落，以评估环境暴露于被遗弃的 地雷废物对生育结果和儿童发育的影响。这项研究是第一次大规模评估 环境暴露和部落人口的儿童健康是与部落合作进行的。 将帮助建立部落内部的研究能力以及部落工作人员的能力， 进行详细的发展评估。该研究将跟踪入组儿童的发育， 5岁时跟踪神经和身体发育的轨迹或模式， 接触部落土地上或附近废弃的硬岩和铀矿的金属混合物。有 美国西部有161，000个这样的废弃矿井，其中4，000个是废弃的铀矿， 没有围栏，没有标记，儿童可以进入。仅在纳瓦霍部落，就有500多个废弃的铀 自最后一个矿场关闭以来，这些矿场30多年来仍未得到补救。拟议的研究将 通过研究ECHO计划确定的两个关键健康结果重点领域， 产前和幼儿期暴露对1）神经发育和2）肥胖的影响。根据团队的 根据初步研究结果，该研究将重点关注由于暴露于 金属混合物在怀孕期间，以及这种失调可能导致神经发育障碍的机制， 延误和肥胖。这项工作将作为NIH联盟的一部分进行，以研究环境 对儿童健康结果的影响（ECHO），将试图汇集多达50，000名儿童 从现有的出生队列研究中了解毒物、社会、营养和 文化环境对发展轨迹的影响。将美洲原住民群体包括在内将使 财团第一次深入研究如何正常儿童发展的进展，在土著人口， 以及环境逆境如何影响这一过程。美洲原住民的 贫困和失业，缺乏基本的基础设施，包括清洁的饮用水和下水道， 教育完成率较低。然而，他们也有很强的文化认同感，在孩子身上的力量- 来自大家庭的抚养，以及对重要发展里程碑的评价差异， 与帮助克服逆境的韧性的发展有关。因此双方的 包括在这一努力，以了解暴露对这些重要的健康结果的影响，将带来一个 这一观点不仅有助于我们了解美国的发展， 主权部落民族所代表的多样性，但也将有利于部落在通知 制定政策和临床护理，提高儿童发挥最大潜力的能力。

Summary The URGENT Native American ECHO Cohort will build on the active Navajo Birth Cohort Study (NBCS), extending the follow up period beyond the current 12 month protocol, and adding two additional tribes, the Cheyenne River and Oglala Sioux Tribes, to assess the impact of environmental exposures to abandoned mine waste on birth outcomes and child development. The study, the first large-scale assessment of environmental exposures and children’s health in tribal populations is conducted in partnership with tribal communities and will help to build both research capacity within the tribes as well as capacity of tribal staff to conduct detailed developmental assessments. The study will follow development of the enrolled children until age 5 to track trajectories or patterns of neuro- and physical development with respect to environmental exposures to metal mixtures from abandoned hard rock and uranium mines on or near tribal lands. There are 161,000 such abandoned mines in the Western US, 4,000 of them abandoned uranium mines which are often unfenced, unmarked and accessible to children. On Navajo Nation alone, more than 500 abandoned uranium mines remain un-remediated more than 30 years since the closing of the last mine. The proposed research will address two of the key health outcome focus areas identified by the ECHO program through study of the effects of prenatal and early childhood exposure on 1) neurodevelopment, and 2) obesity. Based on the team’s preliminary findings, the research will focus on dysregulation of immune function as a result of exposure to metal mixtures during gestation, and mechanisms by which this dysregulation can lead to neurodevelopmental delays and obesity. The work will be conducted as part of the NIH Consortium to study Environmental Influences on Child Health Outcomes (ECHO) which will attempt to bring together as many as 50,000 children from existing birth cohort studies to understand the complex interactions of toxicant, social, nutritional, and cultural environments on developmental trajectories. Inclusion of the Native American Cohort will bring to the Consortium the first in-depth look at how normal child development progresses in Native populations in addition to how environmental adversity affects that course. Native Americans have far greater rates of poverty and unemployment, lack much essential infrastructure including clean drinking water and sewers, and have lower educational completion rates. However, they also have strong cultural identities, strength in child- rearing from extended families, and differences in appreciation of significant developmental milestones that have been associated with the development of resilience that helps in overcoming adversity. Therefore, their inclusion in this effort to understand the effects of exposure on these important health outcomes will bring a perspective that will serve not only to inform our understanding of development in the US through inclusion of the diversity represented by the sovereign tribal nations, but will also be of benefit to the tribes in informing the development of policies and clinical care that enhances the ability of children to reach their maximum potential.