Screening for Preterm Birth: Potential for a Metabolomics Biomarker Panel

Abstract

The aim of this preliminary study was to investigate the potential of maternal serum to provide metabolomic biomarker candidates for the prediction of spontaneous preterm birth (SPTB) in asymptomatic pregnant women at 15 and/or 20 weeks’ gestation. Metabolomics LC-MS datasets from serum samples at 15- and 20-weeks’ gestation from a cohort of approximately 50 cases (GA < 37 weeks) and 55 controls (GA > 41weeks) were analysed for candidate biomarkers predictive of SPTB. Lists of the top ranked candidate biomarkers from both multivariate and univariate analyses were produced. At the 20 weeks’ GA time-point these lists had high concordance with each other (85%). A subset of 4 of these features produce a biomarker panel that predicts SPTB with a partial Area Under the Curve (pAUC) of 12.2, a sensitivity of 87.8%, a specificity of 57.7% and a p-value of 0.0013 upon 10-fold cross validation using PanelomiX software. This biomarker panel contained mostly features from groups already associated in the literature with preterm birth and consisted of 4 features from the biological groups of “Bile Acids”, “Prostaglandins”, “Vitamin D and derivatives” and “Fatty Acids and Conjugates”.

Association between phospholipid metabolism in plasma and spontaneous preterm birth: a discovery lipidomic analysis in the cork pregnancy cohort

“…In conclusion, this study reports reduced glycerophospholipids and sphingolipids at 20 weeks' gestation, prior to the onset of sPTB in women in the Cork SCOPE study. Our findings confirm and extend findings by Considine et al (2019), suggesting convergent metabolomic and lipidomic pathways in the same cohort of women (Considine et al 2019), which may serve as potential therapeutic targets or putative markers for the prediction of sPTB. Further research is needed to validate these findings in independent pregnancy cohorts.…”

“…2). In support of our observations in sPTB in SCOPE Cork, a recent metabolomic profiling study in the same cohort of women implicated bile acids, prostaglandins and Vitamin D as differentially expressed at 15 and 20 weeks' gestation (Considine et al 2019). This independent study which was performed at the University of Manchester, profiled metabolites using alternative extraction protocols (Dunn et al 2011) and LC-MS/MS analyses.…”

Do nuclear magnetic resonance (NMR)-based metabolomics improve the prediction of pregnancy-related disorders? Findings from a UK birth cohort with independent validation

“…Similarly, a study reported that a panel of four mass spectrometry-derived metabolites could predict spontaneous PTB with a partial AUC (i.e. an alternative to AUC, whereby only the regions of ROC space where data are observed are included) of 12.6 in 105 women [ 27 ]. These studies did not compare their models to the existing risk factors or undertake external validation.…”

Do nuclear magnetic resonance (NMR)-based metabolomics improve the prediction of pregnancy-related disorders?

“…Similarly, a study reported that a panel of four mass-spectrometry derived metabolites could predict spontaneous PTB with a partial AUC (i.e. an alternative to AUC, whereby only the regions of ROC space where data are observed are included) of 12.6 in 105 women 27 . These studies did not compare their models to existing risk factors or undertake external validation.…”