Prenatal Arsenic Exposure and Birth Outcomes in a Longitudinal Birth Cohort in Bangladesh

Abstract

This research provides an in-depth investigation into the associations between prenatal arsenic exposure and adverse birth outcomes with a view to mechanistically explain these associations by exploring miRNA expression profiles in the placenta. The first part of the dissertation investigates the effects of prenatal arsenic exposure, adolescent marriage, and pregnancy weight gain on preterm birth in Bangladesh. Because these factors of environmental, societal and maternal health origin often coexist and are highly prevalent in the South and South-East Asia, including Bangladesh, findings from this research may provide insights into effective intervention strategies for reducing preterm birth burden in this region. The second part of the dissertation critically evaluates the causal association between prenatal arsenic exposure and birthweight in relation to shortening of gestation and intrauterine growth restriction- the two main causal processes of low birthweight. Using quantile causal mediation analysis approach, we estimated pathway specific effects of arsenic exposure on birthweight and evaluated whether the susceptibility of arsenic exposure varies by infant birth sizes. In the third chapter we delved into identifying placental microRNA markers that regulate birthweight in presence to environmental arsenic exposure. Using epigenome-wide approach, we identified that placenta-derived miRNAs not only regulate birthweight by determining the length of gestation but also modulating the susceptibility of environmental toxicants on fetal growth. This dissertation presents a more complete understanding of the associations between prenatal arsenic exposure and birthweight by contributing new knowledge to explain underlying mechanisms of this complex exposure-outcome relation.