PRENATAL FINE PARTICULATE MATTER (PM2.5) AND POLYCYCLIC AROMATIC HYDROCARBON (PAH) EXPOSURES AND THEIR ASSOCIATION WITH BIRTHWEIGHT IN SOUTHERN INDIA

项目摘要/摘要 空气污染是印度全国疾病负担的主要风险因素，估计导致1.17 2019年成人死亡100万人，新生儿死亡11.6万人。印度各地的环境空气污染正在稳步增加 特大城市和近100%的人口暴露在不安全水平的细颗粒物中 (PM2.5)。此外，暴露在空气中的有毒物质，如多环芳烃(PAHs)，可能会 由于来源无处不在和排放量高，在印度城市普遍存在，但暴露于 空气有毒物质的特征仍然很差。空气污染对孕妇及胎儿发育的影响 对印度有巨大的影响，在印度，低出生体重(LBW&lt；2.5公斤出生体重)的流行率是 已经很高了(各州15%到30%)。尽管健康无处不在，有害PM2.5和多环芳烃暴露以及 LBW的高患病率，将这些暴露与不良妊娠结局联系起来的证据一直有限 印度。为了解决这一证据差距，该研究建议建立一个300名孕妇的城市队列 在金奈(印度南部的一个特大城市)通过以下途径检查怀孕期间PM2.5和PAHs的暴露情况 个人监测和生物标记物测量，并检查与出生体重的关系。建议数 研究建立在主办机构通过以前的NIH支持建立的广泛能力的基础上 项目。这项研究将从SRI Ramachandra医院的门诊招募300名孕妇 (申请者所在研究所)，进行三次24小时PM2.5和PAHs个人暴露测量， 每三个月使用一次可穿戴取样器，并评估PM2.5组分的氧化潜力 (PM-OP)及其与PM2.5和PAHs的关系尿中多环芳烃代谢物水平(2- 和8-氧-7，8-二氢-2‘-脱氧鸟苷(8-OHdG)，氧化的生物标志物 每三个月将测量损伤，脐带血中将测量白细胞端粒长度(LTL 血。这将允许对PM2.5、多环芳烃、PM-OP、 尿液生物标志物(PAH代谢物和8-OHdG)和端粒长度。在100人的子集上 队列，新鲜空气腕带将用于提供个人暴露于多环芳烃的衡量标准，并将 与暴露和影响的其他指标一起进行评估。最后，PM2.5和PAHs对环境的不同影响 足月儿低出生体重将使用单污染、双污染和多污染模型进行检测。这项研究将加强 出生前PM2.5和多环芳烃暴露与出生体重的有限可用暴露反应证据 同时还确定了潜在的易受影响的暴露窗口。职业发展活动将重点放在 关于新的暴露评估技术、基于质谱学的技术的高级培训 生物标志物分析、回归分析和多污染物模型。增加的调查员能力将 允许研究超越传统PM与大众相关的健康影响，以解决多种环境暴露问题 在印度城市的高曝光率环境中占主导地位。

PROJECT SUMMARY / ABSTRACT Air pollution is a leading risk factor for the national disease burden in India, resulting in an estimated 1.17 million adult and 116,000 neonatal deaths in 2019. Ambient air pollution is increasing steadily across Indian megacities and nearly 100% of the population experience exposures to unsafe levels of fine particulate matter (PM2.5). Further, exposures to air toxics such as polycyclic aromatic hydrocarbons (PAHs) are likely to be widespread in urban India on account of ubiquity of sources and high volume of emissions, but exposures to air toxics remain poorly characterized. Impacts of air pollution on pregnant women and the developing fetus have tremendous implications for India where, the prevalence of low birth weight (LBW <2.5 kg birthweight) is already high (15 to 30% across states). Despite the ubiquity of health damaging PM2.5 and PAHs exposure and high prevalence of LBW, evidence linking these exposures to adverse pregnancy outcomes has been limited in India. To address this evidence gap, the study proposes to establish an urban cohort of 300 pregnant women in Chennai (a megacity in southern India) to examine pregnancy period exposures to PM2.5 and PAHs through personal monitoring and biomarker measurements and examine associations with birthweight. The proposed research builds on the extensive capacities at the host institution created through previous NIH supported projects. The study will recruit 300 pregnant women from outpatient clinics of Sri Ramachandra Hospital (applicants host institute), conduct 24-hour personal exposure measurements for PM2.5 and PAHs three times, once during each trimester using a wearable sampler and assess the oxidative potential of the PM2.5 fractions (PM-OP) by acellular assays and its relationship with PM2.5 and PAHs. Urinary levels of PAH metabolites (2- naphthol and 1-hydroxypyrene) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-OHdG), a biomarker of oxidative damage will be measured during each trimester and leukocyte telomere length (LTL) will be measured in cord blood. This will allow an evaluation of the individual and interactive associations between PM2.5, PAHs, PM-OP, urinary biomarkers (PAH metabolites and 8-OHdG) and telomere length. On a 100-person subset of the cohort, Fresh Air wristbands will be used to provide a measure of personal exposure to PAHs and will be evaluated with other measures of exposure and effect. Finally, the differential effects of PM2.5 and PAHs on term low-birth weight will be examined using single, two and multipollutant models. The study will strengthen the limited available exposure-response evidence for prenatal PM2.5 and PAH exposures and birthweight in India while also identifying potential vulnerable exposure windows. Career development activities will focus on advanced training in novel exposure assessment techniques, mass spectrometry-based techniques for biomarker analysis, regression analysis and multipollutant modeling. The increased investigator capacities will allow research beyond traditional PM mass-related health effects to address multiple environmental exposures that predominate in high exposure settings of urban India.