Metabolomics Profiling for Identification of Novel Potential Markers in Early Prediction of Preeclampsia

Abstract

Objective The first aim was to investigate specific signature patterns of metabolites that are significantly altered in first-trimester serum of women who subsequently developed preeclampsia (PE) compared to healthy pregnancies. The second aim of this study was to examine the predictive performance of the selected metabolites for both early onset [EO-PE] and late onset PE [LO-PE].MethodsThis was a case-control study of maternal serum samples collected between 8+0 and 13+6 weeks of gestation from 167 women who subsequently developed EO-PE n = 68; LO-PE n = 99 and 500 controls with uncomplicated pregnancies. Metabolomics profiling analysis was performed using two methods. One has been optimized to target eicosanoids/oxylipins, which are known inflammation markers and the other targets compounds containing a primary or secondary biogenic amine group. Logistic regression analyses were performed to predict the development of PE using metabolites alone and in combination with first trimester mean arterial pressure (MAP) measurements.ResultsTwo metabolites were significantly different between EO-PE and controls (taurine and asparagine) and one in case of LO-PE (glycylglycine). Taurine appeared the most discriminative biomarker and in combination with MAP predicted EO-PE with a detection rate (DR) of 55%, at a false-positive rate (FPR) of 10%.ConclusionOur findings suggest a potential role of taurine in both PE pathophysiology and first trimester screening for EO-PE.

AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia

“…Alterations in metabolic substrates and a consequent energy crisis have been thought to trigger the clinical manifestations of PE. Although the metabolite profile of PE has been studied in various biosamples, including peripheral blood, urine and amniotic fluid [30][31][32], the metabolite characteristics of the placenta in PE are still largely unknown.…”

Validation of metabolomic models for prediction of early-onset preeclampsia

“…They have, however reported significant differences in the blood or urine metabolome of pregnant women who have or are destined to develop PE. 16,17,[29][30][31][32] The different biomarkers reported are partly a consequence of the different metabolomic platforms used (ie, NMR vs mass spectrometry), which tend to identify different kinds of compounds. Variation in results can also be ascribed to different specimen types, gestational age at testing, category, and indeed, definitions of PE used.…”

Association of maternal prepregnancy BMI with metabolomic profile across gestation

“…49 Kuc et al reported 308 lower levels of asparagine in pre-eclamptic pregnant women. 50 Glutamate and aspartate are the only AA 309 which are not actively transported across the placenta 48 and glutamate from the fetal circulation is taken 310 up into the placenta. 51 Thus, higher maternal levels of glutamate are not depleted via fetal transport 311 similar to other AA but likewise, higher maternal glutamate levels may not influence fetal growth.…”