Maternal exposure to criteria air pollutants during early pregnancy and congenital heart defects in offspring.

摘要

Toxicological and epidemiological literature suggests that maternal exposure to air pollutants during pregnancy has the potential to disrupt fetal development, resulting in adverse pregnancy outcomes in offspring. The goal of this dissertation was to explore the relationship between maternal exposure to carbon dioxide, nitrogen dioxide, ozone, coarse and fine particulate matter and sulfur dioxide during the window of fetal cardiac development, weeks 2 through 8 of pregnancy, and congenital heart defects (CHDs) in offspring within the context of the National Birth Defects Prevention Study (NBDPS), a large population-based case-control study. Specific Aim 1 sought to explore the relationships between pollutants and individual CHDs in a novel way, by assessing individual weeks of exposure in addition to a seven-week summary measure and utilizing hierarchical regression models to address the issue of multiple inference. These relationships were also explored in a multipollutant context by using principal components analysis to construct source-factor models. Positive associations were observed for several pollutants and CHDs in both single-pollutant and source-factor analyses. Assessing individual weeks of fine particulate matter exposure revealed potential windows of greater susceptibility, including week 2 for tetralogy of Fallot (odds ratio, OR 1.98 95% confidence interval, CI 1.11,3.46) and week 5 for pulmonary valve stenosis (OR 1.83 95% CI 1.08,3.12) when contrasting women in the highest and lowest deciles of exposure. Women who used supplements containing folic-acid, a methyl donor involved in the regulation of DNA methylation processes, had lower odds of offspring with CHDs associated with fine particulate matter exposure than women who did not report taking supplements, suggesting a potential mechanism underlying these associations. Specific Aim 2 sought to compare the monitor-derived estimates of fine particulate matter and ozone exposure to model-derived estimates with greater temporal and spatial resolution. This comparison revealed little effect of the greater temporal resolution and found observed differences in results using monitor-based versus model-based exposure estimates potentially attributable to the spatial differences in the composition of particulate matter. The findings of this dissertation support further avenues of research including how risk of CHDs varies by the composition of fine particulates and the quality of maternal nutrition.