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.

PROJECT NARRATIVE Impacts from air pollution exposures on adverse pregnancy outcomes can have serious consequences for populations in low and middle income countries (LMICs) struggling to improve maternal and child health in the face of multiple risk factors. The proposed research will use novel exposure assessment tools to generate extensive (environmental and biomarker based) pregnancy period exposure information for PM2.5 and PAHs in relation birth outcomes in India. Evidence from the study will inform monitoring and evaluation efforts directed at maternal and child health in India and other LMICs.