Pregnant women are exposed to a complex mixture of environmental agents implicated as endocrine disrupting chemicals (EDCs) as shown by experimental studies (Gore et al., 2015). Previous studies report widespread exposure to multiple environmental phenols (EPs), including bisphenols, parabens, benzophenones, and triclosan (TCS), among pregnant women in the U.S. (Aung et al., 2019; Kim et al., 2021; Lee-Sarwar et al., 2018; Mortensen et al., 2014; Polinski et al., 2018). EPs cross the placenta and have been measured in umbilical cord blood, with transplacental transfer ratios exceeding 1.0 in some studies, suggesting accumulation in the fetal compartment (Bloom et al., 2022). Toxicologic and epidemiologic literature implicate some EPs as sex-steroid and thyroid hormone disruptors (Mustieles et al., 2020, 2023; Pulcastro and Ziv-Gal, 2024; Weatherly and Gosse, 2017), modulators of inflammation (Sturla Irizarry et al., 2024; Wu et al., 2022) and oxidative stress inducers (Lan et al., 2022; Pollack et al., 2020). These endocrine, inflammatory, and oxidative stress effects may have critical implications for pregnancy maintenance and preterm birth (PTB) (Johns et al., 2017; Kek et al., 2024; Stagnaro-Green, 2009). PTB, defined as gestational age of <37 weeks at delivery, is the most significant risk factor for neonatal and infant mortality and morbidities, increases the likelihood of developmental delays in childhood, and inflates risks of adverse health outcomes across the lifespan (Morniroli et al., 2023)
The results of previous epidemiologic studies suggest that prenatal exposure to EPs may increase PTB risk, but the results have been inconsistent (Kek et al., 2024). For example, a recent study of couples using in vitro fertilization (IVF) reported greater PTB risk in association with higher maternal urinary bisphenol A (BPA) and bisphenol S (BPS), but a lower risk associated with higher maternal urinary benzophenone-3 (BP-3) and TCS (Zhang et al., 2021). Other studies have also shown contradictory associations between prenatal exposure to EPs and PTB or gestational age at delivery (Fu et al., 2024a, 2024b; Teiri et al., 2022).
Moreover, experimental studies suggest additive and synergistic endocrine-disrupting effects associated with joint exposure to mixtures of EPs, after no observed effect level doses for individual chemicals (Kunz and Fent, 2006; Silva et al., 2002; van Meeuwen et al., 2008). Similarly, the associations of individual urinary EPs with PTB can differ from mixtures (Fu et al., 2024a, 2024b; Guo and Zhu, 2023), and thus, multipollutant and mixture effects of EPs may be helpful tools to inform human health risk assessments (Shaffer et al., 2025)
Minoritized populations experience inflated risks of PTB relative to non-Hispanic white (NHW) populations in the US, especially among people who identify as non-Hispanic Black (NHB) race and ethnicity (Barreto et al., 2024; Manuck, 2017; Osterman et al., 2024). “Race,” is a social construct, used here as a surrogate for individual and systematic lived experiences resulting from complex prior and ongoing historical processes in the US that are based (primarily) on self-identified racial grouping (Cerdeña et al., 2022; Payne-Sturges et al., 2021). Environmental toxicants may be a stressor that plays a causal role in the excess PTB risk experienced by NHB women (Aung et al., 2019; Kim et al., 2021; Lee-Sarwar et al., 2018; Mortensen et al., 2014; Polinski et al., 2018). Differences in the use, costs, and availability of consumer products and pre-packaged and fresh foods, residential proximity to waste and industrial sites, and occupation can lead to differences in the patterns and levels of exposure to EPs among NHB and other minoritized groups (Pacyga et al., 2019; Zota and Shamasunder, 2017). A recent study of pregnant women from across the US reported higher urinary methyl paraben (MePb), ethyl paraben (EtPb), propyl paraben (PrPb), and BPA among NHB compared to NHW women while urinary BP-3 was higher among NHW than NHB women (Bloom et al., 2025).
Psychosocial stress and institutionalized racism may potentiate the toxicity of EPs as a potential mechanism for observed differences in associations with birth outcomes (Burris et al., 2019; James-Todd et al., 2016; Vesterinen et al., 2017). Yet, there are few data to estimate racial and ethnic differences in associations between exposure to widely distributed mixtures of endocrine disrupting EPs with PTB. We used data from the prospective Reproductive Development Study to help address this issue. We hypothesized that associations between mixtures of urinary EPs and PTB would differ between NHW and NHB pregnant women.
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