Fetal growth restriction is an important risk factor for future child and adult morbidity and mortality. Thus, un- derstanding biological mechanisms and preventing exposures during pregnancy that can impact fetal growth have important implications for future child and adult health. Outdoor air pollution has been deemed a signifi- cant health risk contributing annually to 3.2 million premature deaths and 76 million years of healthy life lost globally. Work by our group and others have shown associations between increased air pollution and de- creased birth weight (a proxy of fetal growth restriction). In our previous R01 study, we found that when the ambient concentrations of particulate matter and gaseous pollutants were substantially reduced during the 2008 Beijing Olympics (August 8-September 24; 47 days), babies born to pregnant women living in Beijing whose 8th month of pregnancy was during this period, were 23g (95% CI = 5g, 40g) larger than babies born to pregnant women with their 8th month of pregnancy during the same calendar dates in 2007 or 2009. However, the biological mechanisms by which late pregnancy exposure may impair fetal growth (hence birth weight) are largely unknown to date. It is well appreciated that oxidative stress and inflammation can alter growth and de- velopment in utero, with both associated with preeclampsia and fetal growth restriction. Metabolic deficiencies have also been associated with fetal growth restriction. A factor that may mediate interactions between these pathways is the growth and development of the placenta, the conduit, controller, and anchor for the growth and development of the fetus. Alterations in placental growth and circulatory pattern development may have pro- found impacts on the growth of the fetus. Fetal growth is also controlled in part by genes that are genomically imprinted, a unique form of epigenetic regulation resulting in parent-of-origin-dependent methylation and ex- pression. Imprinted genes play a substantial role in placental function, including regulation of nutrient ex- change. With an overall goal to understand the pathophysiologic pathways linking air pollution and birth weight, we propose to enroll 660 newly pregnant women in Beijing, and measure biomarkers of these pathways in ma- ternal blood or urine at 5 visits during pregnancy and at birth, and in cord blood and placental tissue at birth. We will measure internal doses of combustion-generated pollutants at the same visits, and estimate address- specific ambient concentrations of air pollutants throughout pregnancy, to assess personal pollutant expo- sures. The multiple exposure metrics representing different exposure durations allow us to examine critical time windows during which pollutants may have strong effects on biomarkers and birth weight. This will be the first study to simultaneously examine whether air pollution induces changes in biomarkers of these pathways in pregnant women, the placenta, and/or the fetus, the first study to examine effects of air pollution on epigenetic regulation of critical growth regulatory genes in the placenta, and the first to explore whether these pathways mediate any birth weight (i.e. fetal growth) response to air pollution exposure.
This project will examine associations between increased air pollution exposure during pregnancy (using an internal dose marker of air pollution [Benzo-a-pyrene]) and biomarkers of metabolic deficiency, placental development and vascularization, and systemic inflammation and oxidative stress, measured in maternal blood and urine samples of pregnant residents of Beijing women collected at 5 visits during pregnancy, and cord blood, maternal blood, and placental tissue samples collected at birth. We will then estimate the difference in birth weight associated with increased air pollution exposure during pregnancy, and explore whether biomarkers of these mechanistic pathways mediate this air pollution / birth weight association.
