Arsenic Contaminated Water Consumption & Spontaneous Pregnancy Loss in Romania

描述(由申请人提供)：在几项流行病学研究中，母亲暴露于超过十亿分之十(Ppb)的无机砷浓度(IAS)已被确定为临床公认的自发性妊娠丢失的危险因素。迄今报告的大多数研究评估了居住在以大量地下水国际AS污染而闻名的地区的人。一个更大的全球人口，可能包括数千万美国居民，通过饮用水污染暴露于中、轻度IAS浓度；那些低于10ppb的IAS。虽然有限，但人类、动物和体外研究表明，暴露于轻度-中等浓度的饮用水IAS会增加自然妊娠丢失的风险。到目前为止，只有一项研究是在1976-1978年间进行的，研究对象是饮用水IAS暴露量低于10 ppb的人群，并发现临床公认的妊娠自发流产的风险增加了50%。鉴于人类自然丧失临床确认的妊娠的基线风险很高(即12%-24%)，以及接触含有轻-中度IAS污染的饮用水的广泛分布，即使风险略有增加，也会导致大量可归因性事件。我们建议对饮用水IAS暴露与临床确认的妊娠完成时间少于20周的自然流产之间的关系进行初步评估，并评估罗马尼亚西部一个大型城市医疗中心招募参与者和收集数据策略的可行性。罗马尼亚的这一地区以饮用水源受到轻度到中度的IAS污染而闻名，这种污染提供了低于10ppb的大范围接触。此外，在罗马尼亚，产前护理是强制性的，由政府资助，便于几乎完全确定由18-44岁的新怀孕妇女组成的拟议研究人群。我们将采用病例对照研究设计，病例密度抽样150例，对照150例与胎龄(1：1)匹配。由护士管理的问卷收集的个人历史饮用水暴露数据，加上实验室IAS在报告的饮用水来源中的措施，将被用于分配生殖关键窗口的暴露。我们假设，在怀孕前和怀孕期间，通过在家里和工作场所饮用饮用水而暴露于更多的IAS会增加自然流产的风险。我们拟议的研究将提供初步数据，以允许和评估更大规模的多地点验证性研究的最佳方法，以解决这一关于中低饮用水IAS污染和自然妊娠丢失的关键数据差距。这些数据对于保护孕妇及其胚胎和胎儿免受可能致命的广泛风险因素的伤害至关重要。

DESCRIPTION (provided by applicant): Maternal exposure to concentrations of inorganic arsenic (iAs) in excess of 10 parts per billion (ppb) has been identified as a risk factor for clinically recognized spontaneous pregnancy loss in several epidemiologic studies. The majority of the studies reported to date assessed persons residing in regions well-known for substantial levels of groundwater iAs contamination. A far larger global population, likely to include tens of millions of U.S. residents, are exposed to mild-moderate iAs concentrations via drinking water contamination; those less than 10 ppb iAs. Although limited, human, animal and in vitro studies suggest an increased risk for spontaneous pregnancy loss in association with exposure to mild-moderate drinking water iAs concentrations. To date, only one study, conducted from 1976-1978, targeted a population with drinking water iAs exposures less than 10 ppb, and detected a 50% increased risk for spontaneous loss of a clinically recognized pregnancy. Given the high baseline risk for the spontaneous loss of clinically recognized pregnancies among humans (i.e., 12-24%), and the widespread distribution of exposure to drinking water with mild-moderate iAs contamination even a modest increase in risk would incur a substantial number of attributable events. We propose a preliminary evaluation of associations between drinking water iAs exposure and the spontaneous loss of clinically recognized pregnancies of less than 20 weeks completed gestation, and to assess the feasibility of participant recruitment and data collection strategies at a large urban medical center in western Romania. This area of Romania is well-known for mild-moderate iAs contamination of drinking water sources providing a wide range of exposures below 10 ppb. Moreover, prenatal care is compulsory and government funded in Romania facilitating nearly complete ascertainment of the proposed study population comprised of newly pregnant women 18-44 years of age. We will employ a case-control study design with incidence density sampling of 150 cases and 150 controls matched by gestational age (1:1). Individual historical drinking water exposure data collected by nurse-administered questionnaire, augmented by laboratory iAs measures in reported drinking water sources will be used to assign exposure across critical windows for reproduction. We hypothesize that exposures to greater amounts of iAs through the consumption of drinking water at home and at the workplace, prior to and during gestation, will increase the risk for spontaneous pregnancy loss. Our proposed study will provide preliminary data to permit and evaluation of the best approach for a larger multi- site confirmatory study to address this critical data gap concerning low-moderate drinking water iAs contamination and spontaneous pregnancy loss. These data are vital for the protection of expectant mothers and their embryos and fetuses from a possibly lethal and widespread risk factor for loss.