A Prospective Birth Cohort Study Involving Uranium Exposure in the Navajo Nation

描述（由申请者提供）：应社区要求，将制定纳瓦霍出生队列，通过以下具体目标研究纳瓦霍母亲及其后代在环境中接触铀和相关采矿废物对产前、围产期和产后早期健康的影响：目标1：合作设计和进行一项前瞻性流行病学出生队列研究，研究纳瓦霍族母婴对中与铀废物暴露相关的妊娠结局和儿童发育。 1.征求社区、纳瓦霍人和联邦机构的意见，为最终研究设计提供信息，以确保其尊重纳瓦霍文化，并包括解决社区问题的适当措施2。招募1，650名妊娠早期（妊娠早期或妊娠中期早期，如可行）的孕妇，并在整个妊娠和分娩期间对其进行随访（假设妊娠丢失率为10%）。建立一个由1,500名这些妇女的后代组成的出生队列，对他们的出生、生长和神经发育结果进行评估和随访，直到12个月大（在随访的初始阶段）。比较接触铀和相关金属的可能性较高和较低的母亲及其子女的健康终点（由扩大的研究小组最后确定）。目标二：描述队列的流动性、暴露、共同暴露、可能影响结果的人口统计学和文化特征1。测量/估计人类对铀和其他有毒物质的接触，并确定接触途径2。使用地理空间统计数据识别暴露“热点”，作为暴露3的替代物。收集有关易感性的潜在修饰因素的信息，如饮食和心理社会压力目标3：在我们扩大的社区联络小组（CLG）的指导下，并与社区卫生工作者合作，提供关于研究目标和结果的广泛宣传，产前护理，可用的临床服务，以及减轻任何对纳瓦霍人的健康影响。目标4：与纳瓦霍机构合作伙伴合作，发展其环境卫生能力，并制定一项可持续性计划，以继续对这一群体进行跟踪。这项工作将通过与美国毒物和疾病登记署/疾病控制和预防中心的合作协议来完成，并让机构科学家以及社区参与最后设计的开发和实施。研究团队将流行病学，毒理学，数学和建模以及环境评估方面的科学专业知识与纳瓦霍文化和语言专家，传统医学家和纳瓦霍民族机构以及临床护理提供者的参与相结合，以确保不仅尊重设计和实施，而且有效地将结果转化为政策，医疗保健和有效的社区推广和教育。 公共卫生相关性：纳瓦霍社区50多年来一直暴露在铀矿开采的遗留废物中。社区成员担心接触会导致生殖毒性以及儿童发育受损。在发生过铀暴露的其他社区也提出了类似的关切，但没有在人类中进行过明确的研究。在拟议的纳瓦霍出生队列研究中，我们将检查孕妇的生殖结果，跟踪和评估3个月至1岁的孩子，并建立一个系统，允许跟踪到6岁的儿童，以评估铀暴露对生物和心理社会终点的影响。这项研究将由一个由研究科学家、纳瓦霍和联邦机构代表、临床医生以及纳瓦霍文化和语言专家组成的团队使用基于社区的技术进行。

DESCRIPTION (provided by applicant): In response to community requests, a Navajo Birth Cohort will be developed to study the prenatal, perinatal, and early postnatal health effects of environmental exposures to uranium and associated mining wastes on Navajo mothers and their offspring through the following specific aims: Aim 1: Co-operatively design and conduct a prospective epidemiologic birth cohort study of pregnancy outcomes and child development in relation to uranium waste exposures among Navajo mother-infant pairs. 1. Solicit community, Navajo and federal agency input, to inform the final study design to ensure it is respectful of Navajo culture and includes appropriate measures to address community concerns 2. Enroll 1,650 pregnant women in early pregnancy (1st or early 2nd trimester, as feasible) and follow them throughout pregnancy and childbirth (assumes a pregnancy loss rate of 10%) 3. Establish a birth cohort of 1,500 offspring of these women who will be assessed and followed for birth, growth, and neurodevelopmental outcomes to 12 months of age (in the initial phase of follow-up) 4. Compare health endpoints (as finalized by the expanded Research Team) among mothers and their children who are more and less likely to be exposed to uranium and associated metals. Aim 2: Characterize the cohort with respect to mobility, exposures, co-exposures, demographic and cultural characteristics that may influence outcomes 1. Measure/estimate human exposures to uranium and other toxicants, and identify exposure pathways 2. Use geospatial statistics to identify exposure "hot spots" as surrogates for exposure 3. Collect information on potential modifiers of susceptibility, such as diet and psychosocial stress Aim 3: With guidance from our expanded Community Liaison Group (CLG) and collaboration with community health workers, provide extensive outreach on the study goals and results, on prenatal care, available clinical services, and mitigation of any exposure-induced health effects on Navajo. Aim 4: Work with Navajo agency partners to develop their environmental health capacity and to develop a sustainability plan for continued follow-up of the cohort. This work will be accomplished through a cooperative agreement with ATSDR/CDC and involve agency scientists as well as communities in development and implementation of the final design. The Research Team combines scientific expertise in epidemiology, toxicology, mathematics and modeling, and environmental assessment with participation of Navajo culture and language experts, traditional medicinemen, and Navajo Nation agencies as well as clinical care providers to ensure not only respectful design and implementation, but effective translation of the results to policy, health care, and effective outreach and education for communities. PUBLIC HEALTH RELEVANCE: Navajo communities have been exposed to legacy waste of uranium mining for more than 50 years. Community members are concerned that the exposures have lead to reproductive toxicity as well as impaired development in their children. Similar concerns have been raised in other communities where uranium exposures have occurred but no definitive studies have been conducted in humans. In the proposed Navajo Birth Cohort study we will examine the reproductive outcomes in pregnant women, follow and assess their children for 3 months to 1 year of age, and set up a system to allow follow up through childhood age 6 to evaluate the impacts of uranium exposure on biological and psychosocial endpoints. The research will be conducted by a team of research scientists, Navajo and federal agency representatives, clinicians, and Navajo culture and language experts using community-based techniques.