Maternal Urinary Phthalate Metabolites are Associated with Lipidomic Signatures Among Pregnant Women in Puerto Rico

BackgroundPhthalates have been reported to alter circulating lipid concentrations in animals, and investigation of these associations in humans will provide greater understanding of potential mechanisms for health outcomes. Objectiveto explore associations between phthalate metabolite biomarkers and lipidomic profiles among pregnant women (n = 99) in the Puerto Rico PROTECT cohort. MethodsWe measured 19 urinary phthalate metabolites during 24-28 weeks of pregnancy. Lipidomic profiles were identified from plasma samples by liquid chromatography-mass spectrometry-based shotgun lipidomics. Relationships between phthalates and lipid profiles were estimated using compound-by-compound comparisons in multiple linear regression and dimension reduction techniques. We derived sums for each lipid class and sub-class (saturated, monounsaturated, polyunsaturated) which were then regressed on phthalates. Associations were adjusted for false discovery. ResultsAfter controlling for multiple comparisons, 33 phthalate-lipid associations were identified (q-value<0.05), and diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1 were the most strongly associated with multiple phthalate metabolites. Metabolites of di-2-ethylhexyl phthalate, bis(2-ethylhexyl) phthalate, dibutyl phthalates, and diisobutyl phthalate were associated with increased ceramides, lysophosphatidylcholines, lysophosphatidylethanolamines, and triacylglycerols, particularly those containing saturated and monounsaturated fatty acid chains. SignificanceCharacterization of associations between lipidomic markers and phthalates during pregnancy will yield mechanistic insight for maternal and child health outcomes. Impact StatementThis study leverages emerging technology to evaluate lipidome-wide signatures of phthalate exposure during pregnancy. Circulating lipids are critical for biological processes including inflammation, cell-to-cell communication, and metabolism. Therefore, lipid signatures of phthalate exposure provide insight into potential toxicological mechanisms. Characterization of these mechanisms are relevant for informing the etiology of maternal and childrens health outcomes.