Neonatal cord blood oxylipins and exposure to particulate matter in the early-life environment: An ENVIRONAGE birth cohort study

Abstract

Background: As part of the lipidome, oxylipins are bioactive lipid compounds originating from oxidation of different fatty acids. Oxylipins could provide a new target in the developmental origins model or the ability of early life exposure to change biology. Objectives: We studied the association between in utero PM2.5 (particulate matter with aerodynamic diameter < 2.5 μm) exposure and oxylipin profiles in newborns. Methods: Thirty-seven oxylipins reflecting the cyclooxygenase (COX), lipoxygenase (5-LOX and 12/15-LOX), and cytochrome P450 (CYP) pathways were assayed in 197 cord blood plasma samples from the ENVIRONAGE birth cohort. Principal component (PC) analysis and multiple regression models were used to estimate associations of in utero PM2.5 exposure with oxylipin pathways and individual metabolites. Results: A principal component representing the 5-LOX pathway (6 metabolites) was significantly positively associated with PM2.5 exposure during the entire (multiple testing–adjusted q-value = 0.05) and second trimester of pregnancy (q = 0.05). A principal component representing the 12/15-LOX pathway (11 metabolites) was positively associated with PM2.5 exposure during the second trimester of pregnancy (q = 0.05). PM2.5 was not significantly associated with the COX pathway during any time period. There was a positive but nonsignificant association between second-trimester PM2.5 and the CYP pathway (q = 0.16). Conclusion: In utero exposure to particulate matter, particularly during the second trimester, was associated with differences in the cord blood levels of metabolites derived from the lipoxygenase pathways. These differences may indicate an effect of air pollution during in utero life on the inflammatory state of the newborn at birth. Oxylipins may be important mediators between early life exposures and health outcomes later in life.