loading page

Case finding of early pregnancies at risk of preeclampsia using maternal blood leptin/ceramide ratio: multi-omics discovery and validation from a longitudinal study
  • +18
  • Qianyang Huang,
  • Shiying Hao,
  • Jin You,
  • Xiaoming Yao,
  • Zhen Li,
  • James Schilling,
  • Zhen Li,
  • Sheeno Thyparambil,
  • Wei-Li Liao,
  • Xin Zhou,
  • Lihong Mo,
  • Subhashini Ladella,
  • David Fan,
  • John Whitin,
  • Harvey Cohen,
  • Doff McElhinney,
  • Ronald Wong,
  • Gary Shaw,
  • David Stevenson,
  • Karl Sylvester,
  • Xuefeng Ling
Qianyang Huang
mProbe, Inc.

Corresponding Author:qyhuang@mprobe.com

Author Profile
Shiying Hao
Stanford University School of Medicine
Author Profile
Jin You
University of California Riverside
Author Profile
Xiaoming Yao
mProbe, Inc.
Author Profile
Zhen Li
Stanford University School of Medicine
Author Profile
James Schilling
mProbe, Inc.
Author Profile
Zhen Li
Southeast University
Author Profile
Sheeno Thyparambil
mProbe, Inc.
Author Profile
Wei-Li Liao
mProbe, Inc.
Author Profile
Xin Zhou
Pingjin Hospital Heart Center
Author Profile
Lihong Mo
University of California San Francisco Fresno Center for Medical Education and Research
Author Profile
Subhashini Ladella
University of California San Francisco Fresno Center for Medical Education and Research
Author Profile
David Fan
University of California Santa Barbara
Author Profile
John Whitin
Stanford University School of Medicine
Author Profile
Harvey Cohen
Stanford University School of Medicine
Author Profile
Doff McElhinney
Stanford University School of Medicine
Author Profile
Ronald Wong
Stanford University School of Medicine
Author Profile
Gary Shaw
Stanford University School of Medicine
Author Profile
David Stevenson
Lucile Salter Packard Children's Hospital at Stanford
Author Profile
Karl Sylvester
Stanford University School of Medicine
Author Profile
Xuefeng Ling
Stanford University School of Medicine
Author Profile

Abstract

Objective To evaluate whether longitudinal measurements of serological adipokines and sphingolipids can predict preeclampsia early in gestation. Design Retrospective multi-omics discovery and longitudinal validation. Setting Maternity units in two US hospitals. Methods A multi-omics approach integrating genomic and lipidomic discoveries was employed to identify leptin (Lep) and ceramide (Cer) as novel PE early gestational biomarkers. The levels of placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt-1), Lep, and Cer in maternal sera were then determined by enzyme-linked immunosorbent and liquid chromatography-tandem mass spectrometric assays. Main outcome measures Interval from positive prediction to confirmative diagnosis. Results Genomic meta-analysis compiled six PE placental cohorts with 78 PE and 95 non-PE control placentas. The Testing Cohort included sera from 7 non-PE and 8 PE women collected at confirmatory diagnosis. The Validation Cohort included sera from 20 non-PE and 20 PE women collected longitudinally through gestation. Our findings revealed a marked elevation of maternal serum Leptin/Ceramide (d18:1/25:0) ratio from early gestation (a median of 23 weeks) when comparing later PE-complicated with uncomplicated pregnancies. The maternal Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting PE for sensitivity (85% vs. 40%), positive predictive value (89% vs. 42%), and AUC (0.92 vs. 0.52) from 5 to 25 weeks of gestation. Conclusions Non-invasive longitudinal assessment by serological evaluation of Lep/Cer (d18:1/25:0) ratio can case find early pregnancies at risk of preeclampsia, outperforming sFlt-1/PlGF ratio test. Tweetable abstract Non-invasive longitudinal assessment by serological evaluation of Lep and Cer ratio can predict preeclampsia early in gestation.