Metabolomic biomarkers in midtrimester maternal plasma can accurately predict the development of preeclampsia

Abstract

Early identification of patients at risk of developing preeclampsia (PE) would allow providers to tailor their prenatal management and adopt preventive strategies, such as low-dose aspirin. Nevertheless, no mid-trimester biomarkers have as yet been proven useful for prediction of PE. This study investigates the ability of metabolomic biomarkers in mid-trimester maternal plasma to predict PE. A case–control study was conducted including 33 pregnant women with mid-trimester maternal plasma (gestational age [GA], 16–24 weeks) who subsequently developed PE and 66 GA-matched controls with normal outcomes (mid-trimester cohort). Plasma samples were comprehensively profiled for primary metabolic and lipidomic signatures based on gas chromatography time-of-flight mass spectrometry (GC-TOF MS) and liquid chromatography Orbitrap mass spectrometry (LC-Orbitrap MS). A potential biomarker panel was computed based on binary logistic regression and evaluated using receiver operating characteristic (ROC) analysis. To evaluate whether this panel can be also used in late pregnancy, a retrospective cohort study was conducted using plasma collected from women who delivered in the late preterm period because of PE (n = 13) or other causes (n = 21) (at-delivery cohort). Metabolomic biomarkers were compared according to the indication for delivery. Performance of the metabolomic panel to identify patients with PE was compared also to a commonly used standard, the plasma soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio. In the mid-trimester cohort, a total of 329 metabolites were identified and semi-quantified in maternal plasma using GC-TOF MS and LC-Orbitrap-MS. Binary logistic regression analysis proposed a mid-trimester biomarker panel for the prediction of PE with five metabolites (SM C28:1, SM C30:1, LysoPC C19:0, LysoPE C20:0, propane-1,3-diol). This metabolomic model predicted PE better than PlGF (AUC [95% CI]: 0.868 [0.844–0.891] vs 0.604 [0.485–0.723]) and sFlt-1/PlGF ratio. Analysis of plasma from the at-delivery cohort confirmed the ability of this biomarker panel to distinguish PE from non-PE, with comparable discrimination power to that of the sFlt-1/PlGF ratio. In conclusion, an integrative metabolomic biomarker panel in mid-trimester maternal plasma can accurately predict the development of PE and showed good discriminatory power in patients with PE at delivery.

MicroRNA–mRNA Networks in Pregnancy Complications: A Comprehensive Downstream Analysis of Potential Biomarkers

“…The main placental pathologies leading to preeclampsia are impaired spiral artery remodeling and reduced placental perfusion [ 23 ]. Another important factor to keep in consideration is the difficulty in timely and appropriate diagnosis of IUGR and particularly PE, which is mostly diagnosed during the third trimester of pregnancy [ 24 , 25 ]. An early prediction of PE and IUGR can greatly help to improve the management of these disorders.…”

Prediction of pregnancy-related hypertensive disorders using metabolomics: a systematic review

“…Overall, 32 studies were selected: 25 case control studies23–47 and 7 cohort studies48–54 (table 1). Studies from the same research project but evaluating different metabolites43 46 or populations24 28 29 33 36 38 39 were included.…”

“…Studies from the same research project but evaluating different metabolites43 46 or populations24 28 29 33 36 38 39 were included. Most studies were developed in Europe23 25 28 29 31 33 36 38 39 42 43 46 48–52 and North America32 34 35 40 41 44 45 47 54; there was only one research from Latin America,26 two from Oceania24 53 and another three from Asia 27 30 37. Twelve studies have sampled maternal specimens in the first trimester,31 32 34 35 42 43 46 48 50–53 15 studies have sampled in the second trimester,23 24 27 29 30 33 36–39 41 44 45 49 54 four studies have sampled at least two times25 26 40 47 in pregnancy, and one study included women in late third trimester28 (figure 2).…”

“…Studies have defined pre-eclampsia as hypertension developed in pregnancy associated with proteinuria11 13–15 or end-organ dysfunction 12. Although not consistentlly, chronic hypertension or other illnesses,24 27 29 33 36–39 41 45 55 and multiple pregnancies25 27 30 32 33 36 37 39 41 42 45 52 were reasons for participants exclusion. When chronic hypertensive women were included, there were women taking aspirin as prophylaxis 23 53.…”

Chronic dietary erythritol exposure elevates fasting plasma erythritol levels but does not cause weight gain or modify glucose homeostasis in mice

“…3 Serum erythritol is also associated with disease complications including: diabetic retinopathy, nephropathy, arterial stiffness, vascular complications, and preeclampsia. [6][7][8][9][10] Erythritol, which naturally occurs in fruits and fermented foods, is a sugar alcohol that is about 70% as sweet as sucrose. 11 In food production, erythritol is frequently used to sweeten beverages and can be included in nutrition labels as a "natural flavor" at concentrations up to 1.25%.…”