Abstract
Lipidome-wide metabolites may be useful biomarkers of pregnancy outcomes. We sought to characterize maternal lipidomic signatures associated with preterm birth and neonatal anthropometric parameters. Plasma samples were collected 24–28 weeks gestation, and lipidomic profiling was quantified using high-performance liquid chromatography tandem mass spectrometry. Lipid metabolites were analyzed individually and as whole lipid classes and subgroups based on degree of hydrocarbon chain saturation. Associations were estimated using linear and logistic regression. After false discovery adjustment (q < 0.15), four plasmenyl-phosphatidylethanolamines and three free fatty acids associated with increased risk for spontaneous preterm birth. Five phosphatidylinositols, two phosphatidylglycerols, and one phosphatidic acid were associated with large for gestational age neonates. The saturated plasmenyl-phosphatidylethanolamines held the association with increased risk for spontaneous preterm birth. Both the mono- and poly-unsaturated free fatty acids held the association for increased risk for spontaneous preterm birth. Mono- and poly-unsaturated phosphatidylinositols were associated with large for gestational age neonates. Whole lipid classes (plasmenyl-phophatidylcholines and plasmenyl-phosphatidylethanolamines) were associated with increased risk for large for gestational age at delivery. This study provides evidence that finer omics-scale analysis of the maternal lipidome may be more informative biomarkers of pregnancy outcomes compared to whole class level lipid analysis.
Highlights
Lipidome-wide metabolites may be useful biomarkers of pregnancy outcomes
For large for gestational age neonates, sparse-group lasso identified free fatty acids and phosphatidylinositols as most predictive (Supplemental Fig. 3). In this extensive lipidomic analysis, we investigated three hierarchical levels of lipid organization: (1) individual lipidome-wide metabolites, (2) subgroup clustering based on hydrocarbon chain saturation, and (3) whole lipid classes
Using these organizational hierarchies of lipids, we sought to explore their signatures in association with multiple pregnancy phenotypes: preterm birth and its subtype spontaneous preterm birth, gestational age at delivery, birthweight, and neonatal size relative to gestational age at delivery
Summary
We sought to characterize maternal lipidomic signatures associated with preterm birth and neonatal anthropometric parameters. This study provides evidence that finer omicsscale analysis of the maternal lipidome may be more informative biomarkers of pregnancy outcomes compared to whole class level lipid analysis. Sphingolipids are unique in that they contain an amino group bound to hydrocarbon chains, and some are involved in regulating inflammation and immune responses[4] In addition to these differences across lipid classes, there are functional differences within the same lipid classes. Preterm birth—delivery prior to 37 weeks gestation—remains a persistent public health concern and affects approximately 10% of live b irths[9] Social factors such as environmental injustice, income inequality, and systemic racism have led to disparities in rates of adverse pregnancy outcomes[10]. Lipidomic biomarker signatures can yield utility in estimation of fetal growth and neonatal anthropometric parameters
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