Moving toward understanding specific pathways of inflammation in pregnancy: prenatal exposure to consumer product chemicals and changes in plasma eicosanoids

Abstract

Background. Exposure to consumer product chemicals during pregnancy can influence maternal inflammation, making mothers and infants more susceptible to pregnancy-related disorders. These chemicals can differentially affect inflammatory pathways, but specific pathways during pregnancy are not well characterized. Eicosanoids, an important class of lipid mediators that influence key pathways of inflammation, can now be measured in comprehensive lipid panels. We aimed to determine the association between plasma eicosanoids and urinary biomarkers of three classes of consumer product chemicals among pregnant women.Methods. Our data come from a pilot study of 90 pregnant women nested within the LIFECODES birth cohort study. Maternal plasma and urine were collected at up to three prenatal visits. Plasma was analyzed for 61 eicosanoids, which were grouped into biosynthetic pathways defined by the upstream: 1) fatty acid precursor, including linoleic, arachidonic, docosahexaenoic, or eicosapentaenoic acid; and 2) enzyme pathway, including cyclooxygenase, lipoxygenase, or cytochrome P450. Urine was analyzed for three chemical classes, including 12 phthalate metabolites, 12 phenols, and 9 organophosphate flame retardant metabolites (OPFRs). Each eicosanoid-chemical association was examined using repeated measures from generalized additive mixed effects models. Quantile g-computation was used to examine the association between eicosanoids and a simultaneous increase in all chemicals within each class mixture.Results. Both single-pollutant and mixture analyses showed positive associations between phthalates and phenols with specific eicosanoid pathways. The most consistent associations were between phthalate metabolites and eicosanoids produced from arachidonic acid by lipoxygenase or cyclooxygenase enzymes. In the mixture analyses, a quartile increase in all di-2(ethylhexyl)-phthalate metabolites were most strongly associated with prostaglandin E2 (β = 1.61, 95% confidence interval: 0.98, 2.24).Conclusions. We estimate that higher exposure to phthalates and phenols, but not OPFRs, is associated with elevated inflammation-related eicosanoids, which can provide insight into specific exposure-related pathways of maternal inflammation during pregnancy.