Chemical exposures among reproductive age women and health outcomes for women and offspring
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Increasing evidence suggests that ubiquitous exposure to multiple chemical classes, including elements (e.g. metals) and phthalates, can adversely affect maternal and fetal health. The objective of our research was to evaluate the relationship between chemical exposures for reproductive-aged women and fetal and reproductive health outcomes for these women and their children. Specifically, we aimed to investigate associations between maternal exposure to elements and child neurobehavioral outcomes in a prospective pre-birth cohort of women from Massachusetts (Project Viva), and associations between phthalate exposures and uterine leiomyomata (UL or fibroids) incidence in a prospective cohort of premenopausal black women aged 23-35 residing in Detroit, Michigan (Study of the Environment, Lifestyle, and Fibroids, SELF). Three study aims were developed to examine these associations. In the first aim, we identified associations between maternal lead (Pb) exposure during pregnancy and neurobehavioral outcomes in childhood within Project Viva. We utilized 2nd trimester maternal erythrocyte blood samples to characterize prenatal exposure to Pb and estimated associations with parent- and teacher-rated executive function-related behavior and behavioral difficulties at mid-childhood (median 7.7 years) using multivariable linear regression models adjusted for maternal, paternal, and child characteristics as well as element co-exposures. While effect estimates were modest, trends suggested that higher average prenatal erythrocyte Pb levels predicted poorer childhood executive function related behavior and worse behavioral difficulties, as rated by parents responding to the Behavior Rating Inventory of Executive Function (BRIEF) and the Strengths and Difficulties Questionnaire (SDQ) assessments. Results were similar but attenuated for teacher-rated scales. The second aim investigated associations between prenatal exposure to a mixture of multiple elements, including Pb, and neurobehavioral outcomes in mid-childhood. We built on analysis in the first aim within Project Viva and assessed the interactive and joint effects of element mixtures, including essential and non-essential elements (lead, manganese, mercury and selenium) on neurobehavioral outcomes. We conducted Bayesian Kernel Machine regression (BKMR), multivariable linear regression (MLR) and Weighted Quantile Sum (WQS) regression, adjusting for maternal, paternal and child characteristics. Although associations included the null, the BKMR model suggested marginal joint effects of the mixture of Pb, manganese (Mn), mercury (Hg) and selenium (Se) per higher quantile of each element, with higher parent-rated scores indicating worse neurobehavioral performance. Pb and Se were major contributors to the association across all models. Results were attenuated for teacher-rated scales. The third aim evaluated the association between phthalates and UL incidence in SELF. We conducted a case-cohort study of reproductive-age women to examine incidence of UL as detected by vaginal ultrasound. Overall, most individual phthalate metabolites showed weak to moderate inverse associations with UL incidence among obese women, while the associations were null or weakly positive among women with BMI <30. Taken together, the influence of exposure to elements and phthalates on fetal and reproductive health outcomes varied across toxicants. Results suggest that prenatal Pb exposure can adversely affect child behavior, even at levels relevant to the current population concentration, with marginal evidence of adverse effects of the mixture of essential and non-essential elements. Observed findings for phthalates and UL differed across metabolites and among obese women, suggesting mostly null and inverse effects of phthalates on UL that may be influenced by the hormone activity of each phthalate.