Cohort follow-up study of children exposed to arsenic in utero and early childhoo

描述（由申请人提供）：对生命早期暴露于大多数常见环境化学品（包括砷）的后果知之甚少。这构成了一个重大的知识空白，因为我们最近在智利的研究结果表明，生命早期接触砷会导致青年人因肺癌、膀胱癌、肾癌等几种癌症以及心肌梗塞、慢性肾衰竭和慢性呼吸道疾病等非癌症死亡原因而死亡的人数令人不安地增加。砷是一种已知会影响暴露于砷的成年人多个器官系统的显著有毒物质，包括增加几种癌症、心血管疾病、慢性呼吸道疾病和糖尿病的发病率。我们一直在跟踪孟加拉国650名儿童的队列，其中大约一半的儿童在生命早期广泛接触饮用水中的砷，高达1000μg/L，而另一半从未接触过超过10 μg/L的水。到目前为止，我们的重点一直是呼吸道疾病，我们发现7-17岁接触儿童的呼吸道症状明显增加，包括喘息和呼吸急促。我们建议继续跟踪这一独特的儿童队列，不仅要寻找呼吸系统疾病的进展，还要为其他几种重要的慢性疾病增加早期生命影响的其他标志物。这些包括心血管疾病（血压、血脂、体重指数和血红蛋白）、糖尿病（空腹血糖和糖尿）和慢性肾脏效应（肌酐和血清β 2-微球蛋白）的早期标志物和风险因素。我们还计划对乳牙中的砷作为子宫内和儿童早期暴露的生物标志物进行试点调查。研究生命早期砷暴露的影响是公共卫生的优先事项，因为美国和世界各地数百万孕妇和儿童暴露于高于现行饮用水标准10 μg/L的饮用水中的砷。如果进一步的研究证实了我们的初步证据，即早期生活暴露对暴露儿童的长期健康很重要，那么必须更加重视预防早期生活砷暴露。

DESCRIPTION (provided by applicant): Little is known about the consequences of early life exposure to most common environmental chemicals, including arsenic. This constitutes a critical gap in knowledge, since our recent findings from Chile suggest that early life exposure to arsenic results in disturbing increases in young adult mortality from several cancers, including lung cancer, bladder cancer, kidney cancer, as well as non-cancer causes of death, including myocardial infarction, chronic renal failure and chronic respiratory disease. Arsenic is a remarkable toxicant already known to affect multiple organ systems in exposed adults, including increased incidence of several cancers, cardiovascular disease, chronic respiratory disease and diabetes. We have been following a cohort of 650 children in Bangladesh, approximately half of whom had a wide range of exposure to arsenic in drinking water in early life, up to 1000μg/L, while the other half were never exposed to more than 10 μg/L in water. To date, our focus has been on respiratory disease, and we have found a marked increase in respiratory symptoms in the exposed children at ages 7-17 years, including wheezing and shortness of breath. We propose to continue following this unique cohort of children, not only to look for progression of respiratory disease, but also to add additional markers of early life effects for several other important chronic diseases. These include early markers and risk factors for cardiovascular disease (blood pressure, serum lipids, body mass index, and hemoglobin), diabetes (fasting blood sugar and glycosuria), and chronic renal effects (creatinine and serum ß2-microglobulin). We also plan a pilot investigation of arsenic in deciduous teeth as a biological marker for in utero and early childhood exposure. Studying the effects of early life arsenic exposure is a public health priority, since millions of pregnant mothers and children in the US and worldwide are exposed to arsenic in drinking water above the current drinking water standard of 10 μg/L. If further study confirms our preliminary evidence that early life exposure is important to the long-term health of exposed children, then much more attention must be paid to preventing early life arsenic exposure.