Study Design
The overall sample allocation, hypothesis generation, biomarker discovery, independent validation, and panel construction workflows are illustrated in Fig. 1. Our study was conducted in three phases: (1) the discovery phase, which included both in-silico expression analysis of PE and non-PE placentas and comprehensive literature mining to generated the hypothesis that Lep and Cer might be implicated in PE pathophysiology as potential biomarkers; (2) the testing phase, which measured the levels of Lep and Cer in a case-control cohort of PE and non-PE maternal sera sampled at confirmative diagnosis; (3) the validation phase, which determined the levels of Lep and Cer in an independent longitudinal cohort of PE and non-PE maternal sera sampled at different gestational ages.