工业化和城市交通造成的空气污染是威胁健康的重要环境问题。既往研究发现空气污染可增加自然流产、低出生体重、早产和出生缺陷的风险。妊娠期高血压、子痫前期和糖尿病等妊娠并发症严重威胁到母婴健康。我们前期在加州首次发现交通污染与子痫前期的发生有关，但国内外对其他妊娠并发症及空气污染的毒性机制研究甚少。本研究将基于地理信息系统和高分辨率时空模型，将尖端的空气污染暴露评估技术与分子生物学相结合：（1）利用暴露评价体系，建立并验证氮氧化物和PM2.5的暴露模型；（2）在重污染的天津市城区，结合先进的暴露模型、时空活动模式、建筑环境和问卷调查进行病例对照研究；（3）利用分子生物学技术，检测母血和胎盘DNA加合物、DNA甲基化和mtDNA的含量，探讨污染物可能的作用机制。本项目将在空气污染与妊娠并发症的研究方面填补学术空白，并将显著提高合作者在空气污染流行病学领域的研究能力，使中国在该领域的研究走向世界前列

Air pollution is an increasing environmental health problem in China. Studies have linked air pollution with natural or missed abortion, low birth weight, preterm birth, and birth defects. Pregnancy complications such as pregnancy-induced hypertension, preeclampsia, and diabetes are common in pregnant women and can cause severe immediate and long-term health outcomes in both the mother and the infants. We published the first study that linked local traffic-generated air pollution with preeclampsia in a California population. However, up till now, very little is known internationally and in China about the associations between air pollution and other pregnancy complications, let alone mechanisms underlying potential toxicity. In this study, we will combine cutting-edge air pollution exposure assessment techniques (based on geographical information system and advanced spatiotemporal modeling) with molecular mechanism.investigations to examine potential adverse effects of air pollutant mixture on important pregnancy complications (pregnancy-induced hypertension and preeclampsia, and diabetes). We will conduct exposure measurements, and develop and validate air pollution exposure models for both gases (e.g. nitrogen oxides) and fine particulate matter (PM2.5). Sophisticated air pollution exposure assessment, real-time time-activity tracking, built-environment investigation, and detailed questionnaire will be applied to case-control subjects in metropolitan.Tianjin area, where industries and traffic congestions cause a severe air pollution problem. Further, we will use molecular biology methods including the measures of DNA addult, DNA methylation, and mtDNA contents to examine the potential mechanism of air pollution using maternal blood and placenta samples. The results will fill importantr gaps in the literature on the impact of air pollution on major preganncy complication outcomes. The project will also signficnatly enhance the research capability in air pollution epidemiology among the Chinese collaborators and will promote the leadership of China in this reseach area.

本研究按计划书的内容顺利进行，利用环境监测、地理信息系统及遥感信息、和空间统计等先进技术建立了大气污染高分辨率时空模型；研究环境暴露对孕期并发症的影响；并探讨多环芳烃-DNA加和物与孕期并发症的关系。除了获取环保局常规空气污染监测数据，我们进行了高时空分辨率实地测量。我们收集了夏季和冬季室外氮氧化物（N = 96）和臭氧（N = 36）的样品。夏季O3浓度远高于冬季，而NOx和NO正相反。我们研究了可能影响污染的因素（离机场和工业源距离，道路和交通特征，人口和公交站密度，卫星观测的地表温度，绿地和树木覆盖等），并成功开发NOx和NO（交叉验证R2：0.66-0.67）和O3（交叉验证R2：0.78）预测模型。自2017年1月以来，我们每8天在5个地点用滤膜收集细颗粒物（PM2.5），为期一年（260个滤膜）。 关于PM2.5金属和多环芳烃（PAH）浓度的实验室分析正在进行中。我们在天津医科大学总医院和平津医院招募研究参与者。我们已纳入49名先兆子痫病例（收集48例母血，34例脐血和42例胎盘）和49名对照（收集41例母血，29例脐血和36例胎盘），及43名孕期糖尿病例（18例孕中期母血，42例孕晚期母血，43例脐血和41例胎盘）和101名对照（101例孕中期和101例孕晚期母血，99例脐血， 101例胎盘）。我们尽量采集完全生物样本，但不能避免夜间分娩或同时分娩无法收集的情况。我们用IPAD进行20分钟，涵盖106个问题的问卷调查，内容包括基本病人信息、住房、生活方式和行为、环境接触、病史情况、生育相关史、精神刺激、情绪和感情波动等。目前共完成问卷168份（子痫前期病例49份，孕期糖尿病例43份，对照76份）。此外我们还用GPS收集了53名孕妇一周的时空活动模式及46份唾液样本。我们目前基本完成关于NOx和O3模型建立和验证的文章，预期2018年至少写两篇论文，一篇关于PM2.5成分的时空分布和建模，另1-2篇关于环境暴露（如PAH-DNA加合物和空气污染）和结局（如DNA甲基化，mtDNA含量，先兆子痫，妊娠糖尿病）。这项研究将填补当前文献中有关空气污染对妊娠并发症影响的重要空白。