Using liquid chromatography and mass spectrometry to predict potential biomarkers for missed miscarriage and its metabolic pathways in a tertiary center: A cross‐sectional analytic study

Abstract

ObjectiveTo determine and compare the serum metabolites in missed abortion versus normal early pregnancy using ultra‐high‐performance liquid chromatography and tandem time‐of‐flight mass spectrometry, and to determine how these metabolites can be used to predict the potential biomarkers and possible metabolic pathways of a missed abortion.MethodsThe serum of patients with a missed abortion was used as the experimental group and the serum of patients with an induced abortion during normal early pregnancy was used as the control group. Principal component analysis and orthogonal partial least square discriminant analysis were additionally used to observe the difference in metabolite distribution between the two groups. A variable weight value (variable importance in the projection; VIP) obtained from the orthogonal partial least squares discriminant analysis model more than 1 and P less than 0.05 were taken to indicate significant differences in metabolite screening. After this, enrichment analysis of the metabolic pathways of these metabolites was conducted using Fisher precise test in order to find the metabolic pathway with the highest correlation with the differential metabolites.ResultsIn total, 30 patients were included in the experimental group, with 30 patients in the control group. Fifty‐five metabolites (VIP > 1, P < 0.05) with significant differences related to missed abortion were selected, among which 35 metabolites increased and 20 decreased in patients with a missed abortion. KEGG pathway enrichment analysis showed that the four metabolic pathways with the highest correlation were cholesterol metabolism, arginine biosynthesis, cell apoptosis, and the FoxO signaling pathway.ConclusionThe missed abortion serum metabolites and changes in related metabolic pathways reported in this study provide a basis for the early prediction and diagnosis of a missed abortion.