塑化剂邻苯二甲酸二（2-乙基己)酯、邻苯二甲酸二乙酯和双酚A暴露与学龄儿童肥胖流行的前瞻性队列研究

The world-wide and ongoing rise in obesity has become one of the major problems of global public health. The idea that the endocrine-disrupting chemicals in environment could be contributing to the obesity epidemic has brought about the great attention in international academic community and was acknowledged by some government,However,little attention has been paid to this idea until now in China.The obesity epidemic among chinese children is more critical than ever. Our research results indicated that exposure to some of endocrine-disrupting chemicals like DEHP,DEP and BPA was associated with an increase in body size in children of Han-nationality of citizen schools.Therefore, the role of the endocrine-disrupting chemicals like DEHP,DEP and BPA in children obesity is hypothesized.In this study, the prospective cohort study will be conducted to investigate the causal relationship between exposure to plasticizers (DEHP,DEP and BPA) and school children obesity in China。First, the base check will be performed based on the established a few of thousands Han-nationality school children cohort aged 8 to 10 years enrolled in citizen schools from Shanghai, Jiangsu and Zhejiang provinces respectivly. Follow-up study on obesity will be conducted in 1500 participants of normal weight with different levels of exposure during the following 3 years, with collection of data through questionnaire, physical examination and urinary smaples. The causation will be examined in respect of exposure strength, type of obesity and dose-response relationship.

肥胖流行已成为21世纪全球最重要的公共卫生问题之一。环境内分泌干扰物促肥胖流行的观点已引起国际学术界和各国政府的高度关注，但是迄今国内该领域研究很少。中国儿童肥胖问题日益突出。课题组前期研究结果显示：邻苯二甲酸二（2-乙基己）酯（DEHP）、邻苯二甲酸二乙酯（DEP）和双酚A暴露均与汉族学龄儿童肥胖呈正关联。结合国内外最新研究进展，课题组提出"邻苯二甲酸酯类（DEHP、DEP）和BPA具促肥胖效应，可促进儿童肥胖流行"的假说。本研究在已建立的数千例来自上海、江苏海门和浙江玉环等三个城市的汉族学龄儿童队列人群基础上，先进行基线调查研究，筛选1500名体重正常含不同塑化剂暴露水平的8-10岁学龄儿童为研究对象，然后连续随访3年，包括问卷调查、体格检查和尿液样本采集，从暴露强度、肥胖类型、剂量反应关系等方面，分别探讨塑化剂DEHP、DEP和BPA单独/联合暴露与我国城市学龄儿童肥胖发生的因果关系

环境内分泌干扰物促肥胖流行的观点引起国际学术界高度关注。本项目在前期横断面调查研究基础上，以整群抽样方式在江浙沪连续收集458名8-10岁汉族学龄儿童三年晨尿、体检和问卷资料，从暴露强度、肥胖类型和剂量效应关系等角度探讨DEHP、DEP和BPA单独/联合暴露与我国城市儿童肥胖发生的关联关系。研究发现：城市学龄儿童中BPA检出率为98.02%，中位数1.70ug/L，DEHP代谢产物MEHP、MEHHP、MEOHP、MECPP、MCMHP检出率为100%，中位数5.81μg/L~32.70μg/L，DEP代谢产物MEP检出率为100%，中位数为19.92μg/L。在调整人口统计学特征、活动行为、饮食、皮肤接触和肌酐等29个因素后，利用混合线性模型分析，城市学龄儿童全身型肥胖指标BMI水平与尿样中BPA、DEHP代谢产物、∑DEHP和DEP浓度水平的关联不具有统计学意义，儿童腹型肥胖指标腰围WC水平与尿样中MEP浓度有负关联（P=0.005），MEP每上升一个lg单位，WC值减少0.960859单位，儿童腹型肥胖指标腰臀比WHR水平与尿样中MCMHP浓度有正关联（P=0.004），MCMHP每上升一个lg单位，WHR值增加0.022651单位，男性学龄儿童WHR水平与尿样中∑DEHP总浓度有正关联（P=0.023），∑DEHP每上升一个lg单位，WHR值增加0.021286单位，女性学龄儿童WHR水平与尿样中MEP浓度有负关联（P=0.036），MEP每上升一个lg单位，WHR值减少0.016365单位。浓度进行四分位划分，MCMHP的P75、P50、P25组与P0组的WHR平均水平具有统计学差异（P=0.010、0.001、0.023）。线性趋势检验进一步说明尿样中MCMHP浓度、∑DEHP总浓度与WHR平均水平均具有正向线性关系（P=0.002，0.026）。尿样中BPA、DEHP的存在会改变MEP与WC关联强度，最高可提高27.82%，尤其对于男性儿童，BPA暴露导致MEP与WHR呈现负关联（P=0.039）。总之，BPA暴露与儿童肥胖发生没有关联被发现，DEHP暴露与儿童腹型肥胖有正关联，对男性影响更显著，BPA和DEHP暴露增加DEP与儿童腹型肥胖的关联强度。本研究结果为验证DEHP、DEP和BPA致肥胖假说提供重要的人群纵向队列研究基础数据。