Prenatal exposure to phthalates and associations with gestational weight gain and fetal growth trajectories.

项目总结/文摘

PROJECT SUMMARY/ABSTRACT Widespread exposure to ubiquitous endocrine disrupting chemicals, such as phthalates, during pregnancy, a sensitive period in the life course for both mother and baby, is of global concern. Phthalates and their metabolites (PMs) are associated with increased oxidative stress, hormonal disturbances and epigenetic changes that may interfere with maternal gestational weight gain (GWG) and fetal growth patterns. Maternal GWG and fetal growth rates are important as they influence both short and long-term health outcomes of the mother and baby. Further, pregnancy related racial and ethnic disparities in pregnancy outcomes have persisted over time and environmental exposures may contribute to these. Non-Hispanic Black, Hispanic and Asian women have higher concentrations of PMs likely due to the use of specific personal care products. Although several studies have evaluated PM’s effect on birthweight (the end point of fetal growth) or on periods of GWG, few have considered associations between PMs and fetal growth and GWG rates and those that have are subject to methodological limitations. In addition, there is scarcity of evidence regarding associations between mixtures of PMs and adverse health outcomes. Using data from a nested case control study in a racially diverse population (Nulliparous Mothers To Be (nuMoM2b)), and specifically among healthy controls, we will explore associations between PMs and GWG and fetal growth trajectories using sophisticated statistical methods (i.e., growth mixture models, generalized estimating equations and weighted quantile sum regression) which account for multiple measures of both exposures and outcomes, and account for PM mixtures. We propose the following aims: 1) to examine associations between prenatal exposure to PMs (and their mixtures), measured in each pregnancy trimester and a) GWG and b) estimated fetal growth trajectories among 960 healthy pregnant women across the United States; 2) to evaluate modification by race/ethnicity and fetal-sex between PMs and GWG and fetal growth. This will be the first study to evaluate the effect of a ubiquitous environmental exposure on GWG and fetal growth trajectories. Findings from the proposed study are important to identify critical windows of gestation when maternal GWG and fetal growth may be more be more sensitive to insults from PMs. Importantly, this will aid the design of interventions to reduce phthalate exposure levels, inform policies to regulate phthalate concentrations in products, and educate and target women at greatest risk of exposure. Execution of these specific aims will advance NIEHS’s mission to understand the impact of a ubiquitous environmental exposure, phthalates, on salient maternal fetal outcomes. The proposed training plan will be delivered within Columbia University, one of the world’s preeminent research universities, providing skills in environmental exposures including mixtures analysis, maternal child health and advanced analytic methods that will, with the support of an excellent sponsor team, will ensure successful completion of the study aims and prepare me to a career as an independent productive researcher.