Early Life Exposure to Lead, Iron Metabolism Gene Variants, and Impacts on Reproductive and Infant Outcomes.

Although tremendous reductions in lead exposure to the general population has been achieved in most of North America and Europe, worldwide adults and children continue to be exposed to elevated levels through a variety of media and informal sector occupations. Lead exposure has been adversely associated in epidemiological research with a variety of infant health outcomes, though many of the results have been found to be inconsistent between studies. To address study inconsistency, there has been recent interest in identifying particular exposure time points during development which are most critical for particular health outcomes and how personal susceptibility to environmental toxicants may be modified by common genetic mutations. This dissertation addresses these pertinent issues by expanding the scientific understanding of prenatal susceptibility to lead exposure. This dissertation provides the first evidence that lead exposure early in gestation, as reflected by first trimester plasma or whole blood lead, is a better predictor of gestational length when compared to biomarkers of lead exposure taken during the later stages of pregnancy. Additionally, this dissertation demonstrates for the first time, that both infant and maternal polymorphisms in the iron regulatory (HFE H63D and C282Y) and iron transport system (TF P570S) modify the adverse relationship between lead exposure and infant health outcomes, such as birthweight and mental development. Studies in this thesis highlight the importance of the prenatal period for epidemiological studies that associate environmental toxicants with infant health outcomes. Controlling for maternal as well as infant interpersonal genetic variations and timing of exposure poise significant challenges for future research in this area.PhDEnvironmental Health SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/63674/1/dcantonw_1.pd