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，由于暴露于环境污染物，包括但不限于非职业性暴露于铀和其他金属废物，如过去采矿和碾磨作业以及饮用水污染所产生的砷，受到的影响尤为严重。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依赖率上升。虽然AI/AN在基于人群和有针对性的筛查项目中的代表性大大不足，但最近对北方平原AI的研究表明，胎儿酒精谱系障碍的患病率可能是美国普通人群的10倍（May et al，2008）。该项目的目标是与纳瓦霍出生队列研究（NBCS; PI：刘易斯）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共同暴露会协同作用，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），并得到刘易斯博士关于纳瓦霍民族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的验证的支持。铀和砷的暴露将通过家庭环境评估、对暴露历史的广泛调查以及通过对最近暴露的生物监测确认来确定。除母体自我报告外，还将使用一组已确定的（脂肪酸乙酯[FAEE]）和两种新的（乙基葡糖苷酸[EtG]和硫酸乙酯[EtS]）胎粪生物标志物确认PAE。出生时胎粪中FAEE的存在以前曾被报道可预测儿童未来的精神和心理延迟，一组三种生物标志物有望提高测试的灵敏度和特异性。拟议工作的创新在于与既定的NBCS合作，通过利用NBCS资源采用具有成本效益的战略，并在一个已建立的，长达十年的社区和学术伙伴关系中工作。据我们所知，这项拟议的研究是第一次尝试客观地评估产前酒精暴露（PAE）的患病率和PAE与环境毒物在美洲原住民人口之间的相互作用。这两种暴露都是潜在的可改变的风险因素，可能是造成美洲土著社区健康差异和围产期不良结局的关键因素。如果研究结果支持这一假设，则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.