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

描述（由申请人提供）：对于生命早期暴露于最常见的环境化学物质（包括砷）的后果知之甚少。这构成了一个严重的知识缺口，因为我们最近在智利的调查结果表明，生命早期接触砷会导致年轻人因几种癌症（包括肺癌、膀胱癌、肾癌）以及非癌症死因（包括心肌梗死、慢性肾衰竭和慢性呼吸道疾病）而导致的死亡率令人不安地增加。砷是一种显著的有毒物质，已知会影响接触砷的成年人的多个器官系统，包括增加几种癌症、心血管疾病、慢性呼吸系统疾病和糖尿病的发病率。我们一直在跟踪孟加拉国的650名儿童，其中大约一半儿童在生命早期广泛接触饮用水中的砷，最高可达1000 μg/L，而另一半儿童从未接触过超过10 μg/L的饮用水。迄今为止，我们的重点一直放在呼吸道疾病上，我们发现7-17岁受污染儿童的呼吸道症状明显增加，包括喘息和呼吸短促。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慢性疾病的早期生活影响添加额外的标记。这些包括心血管疾病的早期标志和危险因素（血压、血脂、体重指数和血红蛋白）、糖尿病（空腹血糖和糖尿）和慢性肾效应（肌酐和血清ß - 2微球蛋白）。我们还计划对乳牙中的砷作为子宫和儿童早期接触的生物学标记进行试点调查。研究生命早期砷暴露的影响是一项公共卫生优先事项，因为美国和全世界数百万孕妇和儿童接触到的饮用水中的砷含量高于目前的饮用水标准10 μg/L。如果进一步的研究证实了我们的初步证据，即生命早期接触对接触砷的儿童的长期健康很重要，那么必须更加重视预防生命早期接触砷。

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 1000 μg/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.