Associations of maternal blood metal concentrations with plasma eicosanoids among pregnant women in Puerto Rico

Background/aim: Heavy metals are known to induce oxidative stress and inflammation, and the association between metal exposure and adverse birth outcomes is well established. However, there lacks research on biomarker profiles linking metal exposures and adverse birth outcomes. Eicosanoids are lipid molecules that regulate inflammation in the body, and there is growing evidence that suggests associations between plasma eicosanoids and pregnancy outcomes. Eicosanoids may aid our understanding of etiologic birth pathways. Here, we assessed associations between maternal blood metal concentrations with eicosanoid profiles among 654 pregnant women in the Puerto Rico PROTECT birth cohort. Methods: We measured concentrations of 11 metals in whole blood collected at median 18 and 26 weeks of pregnancy, and eicosanoid profiles measured in plasma collected at median 26 weeks. Multivariable linear models were used to regress eicosanoids on metals concentrations. Effect modification by infant sex was explored using interaction terms. Results: A total of 55 eicosanoids were profiled. Notably, 12-oxoeicosatetraenoic acid (12-oxoETE) and 15-oxoeicosatetraenoic acid (15-oxoETE), both of which exert inflammatory activities, had the greatest number of significant associations with metal concentrations. These eicosanoids were associated with increased concentrations of Cu, Mn, and Zn, and decreased concentrations of Cd, Co, Ni, and Pb, with the strongest effect sizes observed for 12-oxoETE and Pb ( beta:-33.5,95 %CI: -42.9,-22.6) and 15-oxoETE and Sn ( beta:43.2,95 %CI:11.4,84.1). Also, we observed differences in metals-eicosanoid associations by infant sex. Particularly, Cs and Mn had the most infant sex -specific significant associations with eicosanoids, which were primarily driven by female fetuses. All significant sex -specific associations with Cs were inverse among females, while significant sex -specific associations with Mn among females were positive within the cyclooxygenase group but inverse among the lipoxygenase group. Conclusion: Certain metals were significantly associated with eicosanoids that are responsible for regulating inflammatory responses. Eicosanoid-metal associations may suggest a role for eicosanoids in mediating metalinduced adverse birth outcomes.