Environmental As, pregnancy, and children's health

值得注意的是，人们对孕妇和儿童长期接触无机砷(InAs)对健康的影响知之甚少，他们通常被认为是最容易受到环境暴露的人。异丙肾上腺素是一种已知的动物致畸物质，特别是在将其甲基化为单甲基丙酸(MMA)和二甲基丙氨酸(DMA)的物种中。我们已经确定了孟加拉国的一个地区(Sonargaon)，那里的饮用水含有独特的广泛的InAs浓度。我们建议进行这些研究，以检验关于Inas对孕妇和儿童的健康影响和代谢的假设。在2001年，通过对约2000名妇女过去妊娠结局的回顾研究，我们将检查InAs暴露、通过测量饮用水和尿As进行评估，以及后来的自然流产和死产之间的关系。在2002年和2003年，我们将招募大约100名怀孕12-20周的妇女来测试这一假设，即通过服用多种维生素或多种维生素+添加叶酸可以促进甲基化。这项随机试验将检测提供此类补充剂前后尿液中InAs、MMA和DMA的排泄情况。第三，在相同的孕妇中，我们将在分娩时描述母体和脐带InAs、MMA和DMA的关系；我们还将检查血浆同囊(E)ine(叶酸和B12状态的标记物)与InAs、MMA和DMA的关系。最后，在2004年和2005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记物之间的关联。

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.