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

描述（由申请人提供）：美国印第安人/阿拉斯加原住民（AI/AN）在历史上经历了关键生殖健康指标的不同比率。此外，许多人工智能部落，特别是在美国西部，受到环境污染物的不成比例的影响，包括但不限于非职业暴露于铀和其他金属废物，如过去采矿和碾磨作业产生的砷，以及饮用水污染。此外，影响许多部落社区的恶劣社会经济条件往往导致酗酒和依赖率上升。虽然AI/AN在以人群为基础和有针对性的筛查计划中代表性不足，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，酒精会与铀和砷的共同暴露协同作用，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博士关于纳瓦霍族铀和砷暴露源的广泛初步数据和Bakhireva博士进行的乙醇生物标志物研究的验证的支持。铀和砷暴露将通过家庭环境评估、对暴露史的广泛调查和对最近暴露的生物监测确认来确定。除了产妇自我报告外，PAE将通过一组已建立的（脂肪酸乙酯[FAEE]）和两种新的（葡萄糖醛酸乙酯[EtG]和硫酸乙酯[EtS]）胎粪生物标志物进行确认。此前有报道称，出生时胎便中FAEE的存在可预测儿童未来的智力和精神运动迟缓，而三种生物标志物有望提高该测试的敏感性和特异性。拟议工作的创新之处在于与现有的国家统计局合作，利用国家统计局的资源，采用具有成本效益的战略，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，这项拟议的研究是第一次尝试客观地评估美国土著人口中产前酒精暴露（PAE）的患病率以及PAE与环境毒物之间的相互作用。这两种暴露都代表了潜在的可改变的风险因素，这可能是导致美洲土著社区健康差距和不良围产期结果的关键因素。如果这一假设得到研究结果的支持，研究结果的影响将超出当前人群。

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.