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. This study investigates the ability of metabolomic biomarkers in mid-trimester maternal plasma to predict PE. In the mid-trimester study population, 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 maternal plasma was comprehensively profiled for primary metabolomic and lipidomic signatures using gas chromatography time-of-flight mass spectrometry and liquid chromatography Orbitrap mass spectrometry. In the at-delivery study population, a retrospective cohort study was conducted using plasma samples collected from women who were delivered in the late preterm period for PE(n=13) or other causes(n=21), and the metabolomic biomarkers in maternal plasma collected at delivery were compared based on the indication of delivery. Performance of the metabolomic panel was compared also to soluble fms-like tyrosine kinase-1(sFlt-1) and placental growth factor(PlGF) in maternal plasma. In the mid-trimester study population, 329 metabolites were identified and semi-quantitated. 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 alone (AUC=0.87[95% CI, 0.78-0.93] vs 0.65[0.55-0.74]; p< 0.005) (Figure) or sFlt-1/PlGF ratio (data not shown). In the at-delivery study population, we confirmed the ability of this biomarker panel to distinguish PE from non-PE, with comparable discrimination power to that of sFlt-1/PlGF ratio (data not shown). Integrative metabolomic biomarker panel in mid-trimester maternal plasma can accurately predict the subsequent development of PE, and also showed good discriminatory power at the time of delivery.
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