孕期饮用水消毒副产物暴露对胎儿生长发育的影响及机制研究

Exposure to disinfection by-products (DBPs) during gestation has been found to cause adverse effects on birth outcomes in animals. However, the findings from human studies are inconclusive. Early pregnancy is critical for the organ differentiation and development of fetus, which represents a critical window of exposure for implications in adverse health outcomes later in life. Based on the assumption that environmental exposure to DBPs during gestation may impair fetal growth by inducing increased oxidative stress, the project will conduct a prospective cohort study to examine the associations of environmental exposure to DBPs during gestation with oxidative stress and fetal growth, in which individuals' exposure levels are accurately and comprehensively estimated using trihalomethanes in blood and haloaceticacids in urine samples collected during early, mid-, and late pregnancy as internal exposure markers and DBPs measurements in tap water during pregnancy as external makers; fetal growth characteristics are repeatedly measured by ultrasound during pregnancy and combined with measurements at birth; and oxidative stress are assessed by measuring markers of oxidative stress in urine and blood samples collected during early, mid-, and late pregnancy. The results will elucidate the effects of environmental exposure to DBPs on fetal growth and related mechanisms, which ultimately provides scientific basis for the risk estimation of environmental exposure to DBPs during gestation.

消毒副产物（disinfection by-products, DBPs）暴露可引起实验动物不良妊娠结局，但孕妇孕期DBPs暴露是否会影响胎儿的生长发育尚无定论。孕早期是胎儿各器官分化发育关键期，胎儿在此期间受外界环境污染的影响最为深远。基于孕期DBPs环境暴露可通过诱导氧化应激影响胎儿生长发育的假说，本项目采用前瞻性队列设计，以孕早、中、晚期血三卤甲烷和尿卤代乙酸含量为内暴露生物标志，结合孕期全程监测的管网水DBPs含量为外暴露标志准确而全面地评估个体不同孕期的暴露水平；以孕期多时点超声检查参数结合新生儿出生结局动态评估胎儿的生长发育；以研究对象孕早、中、晚期体内一系列代表性氧化应激标志表征机体的氧化应激状态。在此基础上分析孕期DBPs环境暴露、体内氧化应激与胎儿生长发育的关联，以探讨DBPs环境暴露对胎儿生长发育的影响及作用机制，为评估孕期DBPs环境暴露的生殖健康风险提供科学依据。

毒理学证据表明，消毒副产物（disinfection by-products，DBPs）暴露可引起实验动物出现不良妊娠结局，但是现有流行病学研究结果不一致，且DBPs的作用机制也不明确。因此，本研究采用前瞻性队列研究方法，共招募了1760名待产孕妇，以孕早、中、晚期血三卤甲烷（trihalomethanes，THMs）和尿卤代乙酸（haloacetic acids，HAAs）为DBPs暴露标志物，探讨孕期DBPs的暴露水平、时间变异与影响因素；测定了不同孕期尿液样本中3种氧化应激标志物浓度，表征孕妇氧化应激状态；以孕期超声检查参数结合新生儿出生结局动态评估胎儿的生长发育水平，并对部分胎儿出生后第3天神经发育水平进行了评估，分析孕期DBPs内暴露水平、氧化应激与胎儿生长发育的关联。结果显示，血THMs、尿HAAs受采样季节、孕妇社会人口学特征、饮食和用水习惯等因素影响；血THMs、尿HAAs与尿氧化应激标志物在孕期内变异较大，单次采样代表孕期平均暴露水平很可能造成暴露的错误分类。孕期THMs暴露与胎儿腹围、股骨长径和超声测量体重间存在负相关，增加了小于胎龄儿发生风险，且孕早期一溴二氯甲烷和孕晚期三氯乙酸暴露与胎儿神经发育水平降低有关。此外，我们也发现了尿氧化应激标志物与血THMs和尿HAAs水平存在显著正相关，且中介了孕中期THMs暴露与孕晚期胎儿股骨长径间的负相关。研究结果提示，孕期DBPs暴露可能影响了胎儿生长发育水平，且氧化应激可能发挥了介导作用。