Environmental As, pregnancy, and children's health

人们对孕妇和儿童长期接触无机砷的健康后果所知甚少，而孕妇和儿童通常被认为是最容易受到环境接触的群体。InAs是一种已知的动物致畸物，特别是在甲基化成一甲基larsinic酸（MMA）和二甲基larsinic酸（DMA）效率低下的物种中。我们已经确定了孟加拉国的一个地区（索纳加翁），那里的饮用水中含有独特的广泛浓度的InAs。我们建议开展这些研究，以检验有关InAs对孕妇和儿童的健康影响和代谢的假设。在2001年，通过对大约2000名妇女过去妊娠结局的回顾性研究，我们将检查InAs暴露之间的关系，通过测量饮用水和尿液中的As来评估，以及后来的自然流产和死产。在-02年和-03年，我们将招募大约100名怀孕12-20周的妇女来测试a甲基化可以通过服用多种维生素或多种维生素+叶酸来促进的假设。这项随机试验将检查在提供这些补充剂之前和之后尿中InAs、MMA和DMA的排泄情况。第三，在同一孕妇中，我们将描述分娩时母体和脐带的InAs、MMA和DMA之间的关系；我们还将研究血浆同囊(e)线（叶酸和B12状态的标志）与InAs、MMA和DMA之间的关系。最后，在-04年和-05年，我们将分别对6岁和10岁的儿童进行横断面研究，以检查InAs暴露与选定的健康结果生物标志物之间的关系。

Remarkably little is known about the health consequences of chronic inorganic arsenic (InAs) exposure in pregnant women and children, typically perceived to be the most vulnerable to environmental exposures. InAs is a known to teratogen in animals, particularly in species that are inefficient in methylating it to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). We have identified a region of Bangladesh (Sonargaon) where drinking water contains a uniquely wide range concentrations of InAs. We propose to conduct these studies which will test hypotheses concerning the health effects and metabolism of InAs in the pregnant women and children. In year -01, through a retrospective study of past pregnancy outcomes in approximately 2000 women, we will examine the relations between InAs exposure, assess through measurements of drinking water and urinary As, and later spontaneous abortion and stillbirth. In years -02 and -03, we will recruit approximately 100 women at 12-20 weeks of gestation to test the hypothesis that As methylation can be facilitated through the administration of multi-vitamins, or multi-vitamins + addition folate. This randomized trial will examine urinary excretion of InAs, MMA and DMA before and after the provision of such supplements. Third, among the same pregnant women, we will describe at delivery the relationships between maternal and umbilical cord InAs, MMA and DMA; we will also examine the relation between plasma homocyst(e)ine (a marker of folate and B12 status) and InAs, MMA and DMA. Finally, in years -04 and -05, we will conduct cross-sectional studies of children aged-6 and 10-years, respectively, to examine association between InAs exposure and selected biomarkers of health outcomes.