Pregnancy is a period of heightened susceptibility to numerous modifiable environmental stressors, especially to one diverse class of endocrine and metabolic disrupting chemicals, ortho-phthalate diesters (commonly known as phthalates) and their replacements. Evidence suggests prenatal phthalate exposure is associated with adverse maternal and child health outcomes in pregnancy, but these health consequences may also persist well beyond gestation. This is concerning, as pregnant women are ubiquitously exposed to phthalates, but also their plasticizer replacements di(isononyl) cyclohexane-1,2-dicarboxylate (DiNCH) and di(2-ethylhexyl) terephthalate (DEHTP) to which exposure is increasing. Based on recent experimental and observational evidence, these replacements may have similar or worse health consequences than the original phthalates. Additionally, pregnant women are not exposed to one phthalate or replacement at a time, but a mixture of these chemicals, which necessitates evaluating associations of multiple phthalates/replacements with our outcomes of interest to understand the potential true impact of real-life exposures. Therefore, the studies presented in this dissertation were designed to identify potential maternal risk factors, gestational hormonal targets, and cardiometabolic health consequences of prenatal exposure to phthalates and their replacements in women enrolled in the Illinois Kids Development Study. Specifically, we evaluated determinants of maternal phthalate/ replacement exposure (Chapter 2), as well as associations of phthalates/replacements with maternal sex-steroid hormones (Chapter 3) and gestational weight gain (Chapter 4). We developed an approach for measuring urinary sex-steroid hormones at multiple gestational timepoints to capture longitudinal changes in associations of phthalates/replacements with hormones. Given the roles of gestational hormones in coordinating critical pregnancy metabolic adaptations, we also addressed the potential involvement of these biological processes in associations between phthalates/replacements and maternal cardiometabolic health, with a focus on gestational weight gain as one clinically-relevant metabolic endpoint. Throughout, various statistical mixtures approaches, including weighted quantile sum regression, quantile-based g-computation, k-means clustering, and principal component analysis, were highlighted as ways to evaluate phthalate/replacement mixtures. The overarching goal of this dissertation was to underscore the importance of considering maternal pregnancy health, highlighting regrettable substitution, and emphasizing the utility of statistical mixtures approaches to address our research questions of interest.
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