大气污染影响先天性心脏病发生的出生队列研究

The impact of air pollution exposure during pregnancy on fetal cardiovascular development is becoming more and more concerned. Congenital Heart Defects (CHD) are results of the combination of genetic and environmental factors, but the causes are not very clear. .On the basis of the birth cohort study in Tianjin, especially on the basis of prenatal diagnosis and screening. We will investigate the potential correlation of air pollution exposure and the fetal cardiovascular development in the follow-up of this prospective cohort study. Atmospheric pollutant concentration of PM2.5, PM10, SO2, NO2, O3, CO will be continuously monitored. Mass concentrations and chemical compositions of PM2.5 and PM10 will be measured continuously for over three years. The Spatial-Temporal model will be used to evaluate the individual exposure based on land utilization, road network data and meteorological data. At the same time, we will explore the mechanism of air pollution on Congenital Heart Defects, and investigate biomarkers of fetal cardiovascular effects, such as the changes of the key signaling pathways, placental function, mitochondrial DNA (mtDNA) methylation and copy number, using the samples of placenta, umbilical cord blood from the nested case-control population. This project will provide basis for early prevention of Congenital Heart Defects, as well as evidence for the influence of ambient air pollution on adverse pregnancy outcomes.

孕期大气污染暴露对胎儿心血管发育的影响受到日益关注，先天性心脏病(Congenital Heart Defects, CHD)是遗传和环境共同作用的结果，但环境因素影响并不明确。本项目拟在已建立的出生队列基础上，依据孕妇的产前诊断，结合胎儿发育情况和妊娠结局，基于研究对象所处区域环境的大气污染物（PM2.5，PM10，SO2，NO2，O3，CO）浓度及颗粒物组分测定，应用Spatial-Temporal模型进行个体暴露评估，进行大气污染与胎儿心血管发育不良影响的关联性分析。同时，选择巢式病例对照人群，应用胎盘、脐血等生物样本，在关键信号通路因子表达，胎盘功能，线粒体DNA（mtDNA）甲基化和拷贝数改变方面探索大气污染对胎儿心血管发育影响的机制，并应用可能的标志物进行风险评估，以期为先天性心脏病早期预防提供基础，也为大气污染对不良妊娠结局的影响提供科学依据。

孕期大气污染暴露对胎儿心血管发育的影响受到日益关注，先天性心脏病(Congenital Heart Defects, CHD)是遗传和环境共同作用的结果，但环境因素影响并不明确。本研究以天津市作为研究地区，采用反距离加权插值法计算研究期间内研究人群的孕期个体颗粒物暴露水平；使用条件logistics回归分析探究孕期可吸入颗粒物与细颗粒物暴露与子代先心病之间的关联，并使用基于条件logistics回归的分布滞后非线性模型计算孕期第1周至第8周颗粒物个体暴露对子代先心病的滞后效应。结果显示，孕早期PM2.5与PM10暴露对子代先心病具有滞后效应，暴露窗口期主要集中在孕期第1-8周，其中PM2.5的暴露窗口期可能早于胚胎心脏发育关键期。此外，本研究分析差异甲基化位点与孕期第1-8周两种颗粒物暴露的关联，探索胎盘组织DNA甲基化位点在孕期颗粒物暴露与子代先心病之间的中介作用。先心病相关的差异甲基化位点与孕期第1-8周PM2.5与PM10暴露有关，部分位点在颗粒物暴露与子代先心病之间存在间接效应，但具体机制仍需探索。本研究为孕期颗粒物暴露对子代先心病影响研究提供了新的流行病学证据，为胎盘组织DNA甲基化在二者之间的中介效应提供新思路与初步研究基础。