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

项目总结/摘要 空气污染是印度国家疾病负担的主要风险因素，估计造成1.17 2019年有11.6万成人和11.6万新生儿死亡。印度各地的环境空气污染正在稳步增加 特大城市和近100%的人口暴露于不安全的细颗粒物水平 （PM2.5）。此外，暴露于空气中的有毒物质，如多环芳烃（PAH），可能是 由于无处不在的来源和大量的排放，印度城市中的空气污染非常普遍， 空气中的有毒物质仍然没有得到很好的描述。空气污染对孕妇及胎儿发育的影响 对印度有巨大的影响，低出生体重（LBW <2.5 kg出生体重）的流行率是 已经很高了（15%到30%）。尽管PM2.5和多环芳烃暴露对健康有害， 低出生体重的高患病率，将这些暴露与不良妊娠结局联系起来的证据有限， 印度为了解决这一证据缺口，该研究建议建立一个由300名孕妇组成的城市队列 在钦奈（印度南部的一个大城市），通过以下方式检查怀孕期间对PM2.5和多环芳烃的暴露情况： 个人监测和生物标志物测量，并检查与出生体重的关联。拟议 研究建立在主办机构的广泛能力基础上，这些机构是通过以前的NIH支持建立的 项目该研究将从斯里兰卡拉玛昌德拉医院的门诊招募300名孕妇 （申请人所在机构），进行三次PM2.5和PAHs的24小时个人暴露测量， 在每个三个月期间使用可穿戴采样器进行一次，并评估PM2.5组分的氧化潜力 （PM-OP）及其与PM2.5和多环芳烃的关系。PAH代谢物（2- 萘酚和1-羟基芘）和8-氧代-7，8-二氢-2 '-脱氧鸟苷（8-OHdG），一种氧化应激的生物标志物 在每三个月期间测量损伤，并测量脐带中的白细胞端粒长度（LTL 血这将允许对PM2.5、多环芳烃、PM-OP、 尿生物标志物（PAH代谢物和8-OHdG）和端粒长度。在一个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措施，并将 与其他暴露和影响的措施进行评估。最后，PM2.5和多环芳烃对 将使用单一、两种和多种污染物模型对足月低出生体重儿进行研究。该研究将加强 产前PM2.5和PAH暴露和出生体重的有限的可用证据， 印度，同时也确定了潜在的脆弱暴露窗口。职业发展活动将侧重于 在新的接触评估技术，质谱技术， 生物标志物分析、回归分析和多污染物建模。调查员能力的提高将 允许研究超越传统的PM质量相关的健康影响，以解决多种环境暴露问题 在印度城市的高暴露环境中占主导地位。

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.