Prenatal exposure to persistent and non-persistent chemical mixtures and associations with adverse birth outcomes in the Atlanta African American Maternal-Child Cohort

Abstract

Background: African Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards. Objective: We examined the individual and mixture effects of non-persistent chemicals and persistent organic pollutants (POPs) on gestational age at birth and birthweight for gestational age z-scores within a prospective cohort of pregnant AAs. Methods: First-trimester serum and urine samples obtained from participants within the Atlanta African American Maternal-Child cohort were analyzed for 43 environmental chemicals, including per-and polyfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides, pyrethroid insecticides, phthalates, bisphenol A, nicotine, and the primary metabolite of delta-9-tetrahydrocannabinol. Linear regression was used to estimate individual associations between chemicals and gestational age and birthweight z-scores (N ranging from 107 to 523). Mixture associations were estimated using quantile g-computation, principal component (PC) analyses, and hierarchical Bayesian kernel machine regression among complete cases (N=86). Results: Using quantile g-computation, increasing all chemical exposures by one quantile was modestly associated with a reduction in gestational age (mean change per quartile increase= −0.47, 95% CI= −1.56, 0.61) and birthweight z-scores (mean change per quartile increase= −0.49, 95% CI= −1.14, 0.15). All PCs were associated with a reduction in birthweight z-scores; associations were greatest in magnitude for the two PCs reflecting exposure to combined tobacco, insecticides, PBDEs, and phthalates. In single pollutant models, we observed inconsistent and largely non-significant associations. Signifance: We conducted multiple targeted exposure assessment methods to quantify levels of environmental chemicals and leveraged mixture methods to quantify their joint effects on gestational age and birthweight z-scores. Our findings suggest that prenatal exposure to multiple classes of persistent and non-persistent chemicals is associated with reduced gestational age and birthweight z-scores in AAs.

Metabolic Perturbations Associated with an Exposure Mixture of Per- and Polyfluoroalkyl Substances in the Atlanta African American Maternal-Child Cohort

“…Metabolomics is the systemic study of all metabolites associated with exogenous exposure and endogenous processes, and has emerged as an innovative and powerful analytical platform in environmental epidemiology. , Recent investigations demonstrate the applicability of using metabolomics as a central platform to link human exposure with internal dose and biological response. − Specifically, an increase in circulating concentrations of PFAS has been consistently associated with several endocrine disruption- and oxidative stress-related pathways. ,,− In one of our recent metabolome-wide association studies (MWAS), we also identified and verified several biomechanisms and biomarkers mediating the association between serum PFAS concentrations and fetal growth restriction . Moreover, in two separate analyses within the same pregnant population, we found an inverse association between prenatal exposure to PFAS, modeled as single chemicals and a mixture, with fetal growth measures. , …”

“…15 Moreover, in two separate analyses within the same pregnant population, we found an inverse association between prenatal exposure to PFAS, modeled as single chemicals and a mixture, with fetal growth measures. 28,29 Despite these promising findings, methodological challenges remain in elucidating the potential biological responses and health effects associated with multiple PFAS chemicals, particularly for critical windows of exposure across the life course. The vast majority of metabolomics studies continue to focus on a single PFAS chemical at a time or the linear summation of PFAS concentrations, which prevents a deeper understanding about potential joint effects and neglects the high correlation of exposure within the PFAS family.…”

“… 15 Moreover, in two separate analyses within the same pregnant population, we found an inverse association between prenatal exposure to PFAS, modeled as single chemicals and a mixture, with fetal growth measures. 28 , 29 …”

Environmental Exposure to Persistent Organic Pollutants and Its Association with Endometriosis Risk: Implications in the Epithelial–Mesenchymal Transition Process

“…Adipose tissue is, therefore, considered the main reservoir of these compounds, accounting for all routes and sources of exposure, and represents a stable and long-term biomarker of exposure to these chemicals [15][16][17]. The relationship between POP exposure and increased risk for this estrogen-dependent disease is biologically plausible since many OCPs and PCBs have been shown to interact with estrogen and/or androgen receptors [18][19][20][21][22], and epidemiological evidence has been published for a variety of hormone-dependent diseases, e.g., breast cancer [23,24], anovulation [25], ovarian function [26,27], infertility [28], preterm birth [29], polycystic ovarian syndrome [30], fibroids [31], and endometriosis [32]. Nevertheless, while some authors pointed out that some POPs might be related to an increased risk for endometriosis [33][34][35], others have not found any association between POP exposure and endometriosis risk [36][37][38].…”

Sex-Specific and Trimester-Specific Associations of Prenatal Exposure to Bisphenols, Parabens, and Triclosan with Neonatal Birth Size and Gestational Age

“…Previous studies on the effects of multiple EDCs on birth outcomes were fragmented and inconclusive. Besides, the relationship between EDCs and outcomes tends to be nonmonotonic, and multicollinearity often exists among mixtures. , These premises limit the usage of traditional logistic regression or multicollinear models. Thus, in the present study, we introduced three novel models, including quantile-based g-computation (QGC), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models, to explore the joint effect of coexposure to bisphenols, parabens, and TCS on birth size and gestational age.…”