Associations between urinary phthalate metabolites and biomarkers of inflammation and oxidative stress in pregnant women

Abstract

Background: Phthalate exposure is prevalent and associated with an array of adverse health effects. We hypothesized that these relationships may be mediated by phthalate-induced increases in systemic levels of inflammation and oxidative stress. In this study we examine the relationship between phthalate exposure and changes in biomarkers of inflammation and oxidative stress during pregnancy. Methods: Pregnant women recruited in the first trimester provided urine and plasma samples at medians of 10, 18, and 26 weeks gestation. C-reactive protein (CRP) and cytokines IL- 1?, IL-6, IL-10, and TNF-? were measured in plasma as markers of inflammation, and 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane (8-Iso) in urine were markers of oxidative stress. As an indicator of exposure, phthalate metabolites were measured in urine samples and levels were averaged across pregnancy. Results: Crude analysis between biomarkers and phthalate levels standardized for specific gravity showed significant positive correlations between CRP and mono-benzylbutyl phthalate (MBzP), mono-butyl phthalate (MBP), and mono-ethyl phthalate (MEP). Correlations were stronger with oxidative stress biomarkers for the same metabolites as well as mono-isobutyl phthalate (MiBP) and mono-carboxypropyl phthalate (MCPP). In models adjusting for specific gravity, maternal age, race/ethnicity, and education level associations with CRP and MBzP remained significant. Relationships between oxidative stress markers and MBzP, MBP, MiBP, MEP, and MCPP retained significance as well. Associations between phthalate metabolites and cytokines were spurious in both crude and adjusted analyses. Conclusions: Markers of inflammation (CRP) and oxidative stress (8-OHdG and 8-Iso) are associated with urinary phthalate metabolites in pregnant women which has relevance for understanding phthalate relationships with reproductive outcomes.