Potential Serum Biomarkers Associated with Premature Rupture of Fetal Membranes in the First Trimester

Premature rupture of the fetal membranes (PROM) is a common and important obstetric complication with increased risk of adverse consequences for both mothers and fetuses. An accurate and timely method to predict the occurrence of PROM is needed for ensuring maternal and fetal safety. Untargeted metabolomics was applied to characterize metabolite profiles related to PROM in early pregnancy. 41 serum samples from pregnant women who developed PROM later in gestation and 106 from healthy pregnant women as a control group, were analyzed. Logistic regression analysis was adjusted to analyze a PROM prediction model in the first trimester. A WISH amniotic cell viability assay was applied to explore the underlying mechanisms involved in PROM, mediated by C8-dihydroceramide used to mimic a potential biomarker (Cer 40:0; O(2)). Compared with healthy controls, 13 serum metabolites were identified. The prediction model comprising four compounds (Cer 40:0; O2, sphingosine, isohexanal and PC O-38:4) had moderate accuracy to predict PROM events with the maximum area under the curve of a receiver operating characteristics curve of approximately 0.70. Of these four compounds, Cer 40:0; O2 with an 1.81-fold change between PROM and healthy control serum samples was defined as a potential biomarker and inhibited the viability of WISH cells. This study sheds light on predicting PROM in early pregnancy and on understanding the underlying mechanism of PROM. Trial Registration: This study protocol has been registered at www.ClinicalTrials.gov, CT03651934, on 29 August 2018 (prior to recruitment).