Consumer ProductChemical Mixtures and Oxylipin-MediatedInflammation and Oxidative Stress during Early Pregnancy: Findingsfrom a Large US Pregnancy Cohort

Consumer product chemicals pose an environmental risk to public health. Exposure during pregnancy to consumer product chemicals, particularly phthalates and phenols, may increase the susceptibility to pregnancy disorders by dysregulating inflammation and oxidative stress. However, existing studies rely on downstream and nonmodifiable markers of these processes. Oxylipins are oxidized lipids that act as key upstream drivers of inflammation and oxidative stress. Importantly, oxylipins are responsive to therapeutic interventions and thus potentially modifiable. Using recent advances in lipidomics and statistical approaches to address both individual chemical biomarkers and their mixtures, we determined associations between early pregnancy biomarkers of consumer product chemical exposure and oxylipins in a large prospective cohort. Overall, our results revealed associations among oxylipins produced across several biosynthetic pathways, suggesting a pattern indicative of dysregulated inflammation and elevated levels of oxidative stress. Phthalate metabolites were the primary drivers of associations, particularly for metabolites of low molecular weight phthalates, often used in personal care products. However, we found similar associations for a biomarker of a phthalate replacement that is increasingly used in consumer products. Our study provides observational evidence of specific physiological pathways that may be dysregulated by exposure to consumer product chemicals, including legacy phthalates and phthalate replacements.