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.

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