Case finding of early pregnancies at risk of preeclampsia using maternal blood leptin/ceramide ratio

The early risk assessment of preeclampsia (PE) remains challenging in current clinical practice. We hypothesized that impending PE events can be predicted, when asymptomatic early in gestation, through the determination of the serum levels of leptin (Lep), a placental functions regulatory cytokine, and ceramide (Cer), a sphingolipid with anti-angiogenic and pro-apoptotic roles. Sera from two independent cohorts of PE and control women were assembled (Testing Cohort: 7 non-PE and 8 PE women sampled at confirmatory diagnoses; Validation Cohort: 20 non-PE and 20 PE women sampled longitudinally through gestation). Our multi-omics approach, integrating global genomic and lipidomic discoveries, revealed a marked elevation of the Lep/Cer (d18:1/25:0) ratio in PE women. Longitudinal analyses of Lep/Cer ratio can predict a median of 23 weeks before PE confirmative diagnosis. Sensitivity, positive predictive value, and AUC of the Lep/Cer (d18:1/25:0) ratio were 85%, 89%, and 0.92. Therefore, serum elevations of Lep/Cer (d18:1/25:0) ratio can be used to assess risk for impending PE during early asymptomatic pregnancies. roles of Cer in mediating the central feeding cascade of Lep. In addition, we obtained 14 and 150 by using the keywords of Pregnancy” and Preeclampsia”, respectively, suggesting correlation of the physiological role of Cer in homeostatic pregnancy as well as its pathological implication in PE. We therefore selected and dihydroceramide (DHCer), its biosynthetic precursor, as the biomarker candidates to generate our and launched the following