Lipid‐inclusive metabolomics of infants born after suspected preterm labor according to whether delivery occurred preterm or at term: A prospective cohort study

OBJECTIVE: To characterize the cord blood metabolic profile of infants born after suspected preterm labor (sPTL) according to whether delivery occurred preterm or at term compared with infants from uncomplicated pregnancies. STUDY DESIGN: Prospective observational cohort study including singleton pregnancies complicated by sPTL and uncomplicated pregnancies. Lipid-inclusive metabolomics was performed by liquid chromatography-mass spectrometry (LC-MS), and data were analyzed using multivariate and univariate approaches. RESULTS: Of 507 detected metabolites, 506 were present in at least 70% of samples and were included in the analysis. Multivariate analyses showed separation between sPTL with preterm delivery and uncomplicated controls, whereas sPTL with term delivery showed an intermediate metabolic profile. Univariate analysis identified 122 metabolites that differed across the three groups after Benjamini-Hochberg correction. The metabolites contributing most strongly to group discrimination were predominantly lipids, including phosphatidylcholines, cholesteryl esters, sphingomyelins, lysophosphatidylethanolamine, and cholesterol-derived hormones. Hierarchical clustering of the top 25 metabolites identified three clusters, with most sPTL pregnancies resulting in term delivery falling within an intermediate cluster. As antenatal corticosteroid exposure was common among pregnancies with sPTL, and as the sample size of the non-exposed subgroup was limited, the study could not reliably disentangle the effects of sPTL from those of corticosteroid treatment. CONCLUSION: Cord blood metabolomic profiles differed between infants from pregnancies complicated by sPTL and infants from uncomplicated term pregnancies. The persistence of an intermediate metabolic profile among infants born at term after sPTL raises the possibility of a metabolic signature associated with the preceding episode of sPTL. However, the observational design and frequent antenatal corticosteroid exposure preclude the attribution of these differences specifically to sPTL. Larger studies with adequate representation of corticosteroid-exposed and non-exposed pregnancies are warranted.