This study aims to investigate small molecule metabolic profiles of pregnant women diagnosed with early-onset preeclampsia and fetal growth restriction and determine if there are underlying pathogenesis-related metabolic pathways.
120 plasma samples were collected from non-pregnant women (n=39), and healthy (n=25), preeclamptic (n=50), and fetal growth restricted (n=6) pregnancies. Samples from pregnant women were collected at 23–33 weeks’ gestation. Metabolomics profiles were determined using Liquid Chromatography Mass Spectrometry (LC-MS). Statistical and pathway analyses were conducted using MetaboAnalyst 5.0. Differential metabolites were selected according to t-test and Variable Importance Projection (VIP) score. VIP score is the rank of metabolites based on their importance in discriminating two groups via Orthogonal Projections to Latent Structures Discriminant Analysis (oPLSDA) model.
The comparison groups of non-pregnant women versus healthy pregnancies and early-onset preeclampsia versus controls respectively had 60 and 68 significantly different metabolites (q value of 0.05 and VIP score ≥ 1). No qualified differential metabolites were found in fetal growth restriction versus controls. The primary changes belonged to amino acids and fatty acids, including cystine, cysteine, methionine, leucine, glutamine, 2-hydroxybutyric acid, oleic acid, and linoleic acid. Principle Component Analysis plots revealed a clear separation among non-pregnant, healthy pregnancies and early-onset preeclampsia groups. Metabolic pathway analysis showed 12 metabolic pathways overrepresented in early-onset preeclampsia, such as aminoacyl-tRNA biosynthesis, arginine biosynthesis, valine, leucine and isoleucine biosynthesis, alanine and aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism. Multivariate Receiver Operating Characteristic curve analysis of early-onset preeclampsia achieved an Area Under the Curve value of 0.95 (95% CI 0.87–0.99) with a five-metabolite-combined model using random forest algorithm.
These findings reveal critical metabolites and metabolic pathways in pregnancy, requiring further studies to explore their roles in early-onset preeclampsia.