CONCLUSIONS
The disruptions of gestational homeostasis involving placenta-related biological networks are important factors contributing to the pathophysiology of PE. Lep, an endocrine regulator of body energy repletion, and Cer (d18:1/25:0), a bioactive metabolic messenger downstream of Lep, were identified by the multi-omics discovery to be significantly up- and down-regulated in the maternal circulation of women with PE. The Lep/Cer (d18:1/25:0) ratio was demonstrated to provide augmented predictive power in differentiating PE from a pregnancy without PE before a confirmatory diagnosis can be made. The maternal Lep/Cer (d18:1/25:0) ratio, with an earlier elevation in gestation, is a superior prognostic marker than the sFlt-1/PlGF ratio. If validated as a laboratory developed test or in vitro diagnostics, the deployment of the Lep/Cer ratio test to assess PE and proactively manage asymptomatic early pregnancies should have profound impact on PE care.