Interactive Effect of Environmental Exposures and Alcohol in the Navajo Birth Coh

描述（由申请人提供）：美洲印第安人/阿拉斯加原住民 (AI/AN) 历来经历过关键生殖健康指标的不同比率。此外，许多人工智能部落，尤其是美国西部的部落，受到环境污染物暴露的影响尤为严重，包括但不限于非职业性接触铀和其他金属废物，例如过去采矿和铣削作业以及饮用水污染产生的砷。此外，影响许多部落社区的不良社会经济条件往往导致酗酒和酒精依赖率上升。虽然 AI/AN 在基于人群和有针对性的筛查计划中的代表性严重不足，但最近对北部平原 AI 的研究表明，胎儿酒精谱系障碍的患病率可能比美国普通人群高 10 倍（May 等人，2008 年）。该项目的目标是与纳瓦霍出生队列研究（NBCS；PI：Lewis）合作，评估产前酒精、铀和砷暴露对 600 名 1 岁纳瓦霍儿童生长和神经认知缺陷的综合影响。核心假设是，酒精与铀和砷的共同暴露会产生协同作用，增加一岁时早期生长和神经发育缺陷的风险。该项目将采用最先进的方法来确认环境暴露和产前酒精暴露 (PAE)，并得到 Lewis 博士关于纳瓦霍族部落铀和砷暴露源的广泛初步数据以及 Bakhireva 博士进行的乙醇生物标志物研究验证的支持。铀和砷暴露将通过室内环境评估、暴露历史的广泛调查以及通过对近期暴露的生物监测确认来确定。除了母亲的自我报告外，PAE 还将通过一组已建立的（脂肪酸乙酯 [FAEE]）和两种新型（乙基葡萄糖醛酸苷 [EtG] 和硫酸乙酯 [EtS]）胎便生物标志物来确认。此前曾有报道称，出生时胎便中 FAEE 的存在可以预测儿童未来的精神和精神运动迟缓，并且一组三种生物标志物有望提高测试的敏感性和特异性。拟议工作的创新在于与已建立的 NBCS 合作，通过利用 NBCS 资源采用具有成本效益的策略，并在已建立的长达十年的社区和学术伙伴关系中开展工作。据我们所知，这项研究是客观评估美洲原住民中产前酒精暴露 (PAE) 患病率以及 PAE 与环境毒物之间相互作用的首次尝试。这两种暴露都代表了潜在的可改变的风险因素，这些因素可能是导致美洲原住民社区健康差异和围产期结局不佳的关键因素。如果研究结果支持这一假设，那么研究结果将产生超出当前人群的影响。

DESCRIPTION (provided by applicant): American Indian/Alaska Natives (AI/AN) have historically experienced disparate rates of key reproductive health indicators. In addition, many AI tribes, especially in the western U.S., have been disproportionately affected by exposure to environmental contaminants, including but not limited to non-occupational exposures to uranium and other metal wastes such as arsenic resulting from past mining and milling operations and also from drinking water contamination. In addition, poor socioeconomic conditions affecting many tribal communities often lead to increased rates of alcohol abuse and dependence. While AI/AN are greatly underrepresented in the population-based and targeted screening programs, recent studies among AI of the Northern Plains suggest that the prevalence of the Fetal Alcohol Spectrum Disorder might be 10-fold higher than in the general U.S. population (May et al, 2008). The goal of this project is to partner with the Navajo Birth Cohort Study (NBCS; PI: Lewis) to assess a combined effect of prenatal alcohol, uranium, and arsenic exposure on growth and neurocognitive deficits in 600 Navajo children at 1 year of age. The central hypothesis is that alcohol will synergize with uranium and arsenic co-exposures to increase the risk of early growth and neurodevelopmental deficits at one year of age. The project will employ the state-of-the-art methods to confirm both environmental exposures and prenatal alcohol exposure (PAE) and is supported by Dr. Lewis's extensive preliminary data on uranium and arsenic exposure sources in the Navajo Nation and validation of ethanol biomarkers studies conducted by Dr. Bakhireva. Uranium and arsenic exposures will be determined through in- home environmental assessments, extensive surveys for exposure histories, and through biomonitoring confirmation of recent exposures. In addition to maternal self-report, PAE will be confirmed with a battery of one established (fatty acid ethyl ester [FAEE]) and two novel (ethyl glucuronide [EtG] and ethyl sulfate [EtS]) meconium biomarkers. The presence of FAEE in meconium at birth has been previously reported to be predictive of future mental and psychomotor delays in children, and a battery of three biomarkers is expected to improve sensitivity and specificity of the test. The innovation of the proposed work lies in partnering wit the established NBCS, employing a cost-effective strategy by leveraging NBCS resources, and working within an established, decade-long, community and academic partnership. The proposed study is, to our knowledge, the first attempt to objectively assess prevalence of prenatal alcohol exposure (PAE) and interaction between PAE and environmental toxicants in a Native American population. Both exposures represent potentially modifiable risk factors which might be the key players contributing to health disparities and poor perinatal outcomes in the Native American communities. If the hypothesis is supported by the study outcomes, the findings would have impact beyond the current population.