Arsenic Contaminated Water Consumption & Spontaneous Pregnancy Loss in Romania

描述（由申请方提供）：在几项流行病学研究中，母体暴露于浓度超过十亿分之十（ppb）的无机砷（iAs）已被确定为临床公认的自发性流产的风险因素。迄今为止报告的大多数研究评估了居住在地下水iAs污染程度很高的地区的人。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轻度-中度iAs浓度;低于10 ppb iAs。尽管有限，但人体、动物和体外研究表明，与暴露于轻度-中度饮用水iAs浓度相关的自发性流产风险增加。到目前为止，只有一项研究，从1976年至1978年进行，针对饮用水中的iAs暴露低于10 ppb的人群，并检测到50%的风险增加自然流产的临床公认的怀孕。考虑到人类临床公认的妊娠自发丧失的高基线风险（即，12-24%），暴露于轻度-中度iAs污染的饮用水的广泛分布，即使风险略有增加，也会引发大量可归因事件。我们提出了一个初步的评估饮用水iAs暴露和自发性损失的临床确认的怀孕不到20周完成妊娠之间的关联，并评估参与者招募和数据收集策略在罗马尼亚西部的一个大型城市医疗中心的可行性。罗马尼亚的这一地区以饮用水源的轻度-中度iAs污染而闻名，提供了低于10 ppb的广泛暴露。此外，产前护理是强制性的，在罗马尼亚由政府资助，这有助于对由18-44岁的新怀孕妇女组成的拟议研究人群进行几乎完全的确定。我们将采用病例对照研究设计，发病密度抽样为150例病例和150例对照，按胎龄（1：1）匹配。通过护士管理的问卷调查收集的个人历史饮用水暴露数据，通过报告的饮用水源中的实验室iAs测量进行补充，将用于分配生殖关键窗口的暴露。我们假设，在妊娠前和妊娠期间，通过在家中和工作场所饮用水暴露于更大量的iAs，将增加自发流产的风险。我们拟定的研究将提供初步数据，以允许和评价更大规模多中心确证性研究的最佳方法，以解决有关低-中度饮用水iAs污染和自发性流产的关键数据缺口。这些数据对于保护孕妇及其胚胎和胎儿免受可能致命和广泛的风险因素的影响至关重要。 公共卫生相关性：这项研究将包括初步评估饮用水与中低浓度无机砷（即，<十亿分之十，ppb），天然存在于地下饮用水源中，以及临床确认的妊娠不到20周的自然流产。在美国和全世界，数百万育龄妇女暴露于饮用水中低-中等浓度的砷，补救技术成本高昂。虽然大量证据表明，饮用水中无机砷含量>10 ppb会增加自然流产的风险，但很少有研究涉及更多人接触的低-中等水平的无机砷。

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. PUBLIC HEALTH RELEVANCE: This study will comprise a preliminary assessment of associations between the consumption of drinking water with low-moderate concentrations of inorganic arsenic (i.e., <10 parts per billion, ppb), naturally present in ground drinking water sources, and the spontaneous loss of clinically recognized pregnancies of less than 20 weeks completed gestation. In the United States and worldwide millions of women of reproductive age are exposed to low-moderate concentrations of arsenic in drinking water and remediation technologies are costly. Although substantial evidence suggests that exposure to levels of inorganic arsenic in drinking water >10 ppb increases the risk for a spontaneous pregnancy loss, very little research has been conducted concerning the low-moderate levels of inorganic arsenic to which a far greater number of people are exposed.