Associations of Maternal Blood Metal Concentrations with Plasma Eicosanoids Among Pregnant Women in Puerto Rico

Abstract

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 is a paucity of research on identifying biomarker profiles linking metal exposures and adverse birth outcomes that may help inform strategies for prevention, detection, and/or intervention. Eicosanoids are important lipid molecules that regulate inflammation in the human body, and there is growing evidence that suggests associations between plasma eicosanoids and pregnancy outcomes. Therefore, eicosanoids are endogenous biomarkers that may aid our understanding of etiologic 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, along with eicosanoid profiles measured in plasma collected at median 26 weeks. Multivariable linear models were used to regress eicosanoids on metals concentrations. Potential effect modification by infant sex was explored using interaction terms.

Results: A total of 63 unique 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 maternal blood metal concentrations. Also, we observed some differences in metals-eicosanoid associations by infant sex. Particularly, Cs and Mn had the most number of infant sex-specific significant associations with the 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 pathway group but inverse among the lipoxygenase pathway group.

Conclusion: Certain metals were significantly associated with eicosanoids that are responsible for regulating inflammatory responses. These eicosanoid-metal associations may suggest a potential role for eicosanoids in mediating metal-induced adverse birth outcomes.

Note:
Funding Declaration: This study was supported by the Superfund Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health (P42ES017198). Additional support was provided from NIEHS grant numbers T32ES007062, P50ES026049, R01ES032203, and P30ES017885 and the Environmental influences on Child Health Outcomes (ECHO) program grant number UH3OD023251.

Conflicts of Interest: None

Ethical Approval: This study was approved by the research and ethics committees of the University of Michigan School of Public Health, University of Puerto Rico, Northeastern University, and participating hospitals and clinics. The patients/participants provided their written informed consent to participate in this study.

Keywords: Metals, Eicosanoids, Pregnancy, Puerto Rico