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Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation.

Publication ,  Journal Article
Huang, Q; Hao, S; You, J; Yao, X; Li, Z; Schilling, J; Thyparambil, S; Liao, W-L; Zhou, X; Mo, L; Ladella, S; Davies-Balch, SR; Zhao, H ...
Published in: BMJ Open
November 25, 2021

OBJECTIVE: This study aimed to develop a blood test for the prediction of pre-eclampsia (PE) early in gestation. We hypothesised that the longitudinal measurements of circulating adipokines and sphingolipids in maternal serum over the course of pregnancy could identify novel prognostic biomarkers that are predictive of impending event of PE early in gestation. STUDY DESIGN: Retrospective discovery and longitudinal confirmation. SETTING: Maternity units from two US hospitals. PARTICIPANTS: Six previously published studies of placental tissue (78 PE and 95 non-PE) were compiled for genomic discovery, maternal sera from 15 women (7 non-PE and 8 PE) enrolled at ProMedDx were used for sphingolipidomic discovery, and maternal sera from 40 women (20 non-PE and 20 PE) enrolled at Stanford University were used for longitudinal observation. OUTCOME MEASURES: Biomarker candidates from discovery were longitudinally confirmed and compared in parallel to the ratio of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) using the same cohort. The datasets were generated by enzyme-linked immunosorbent and liquid chromatography-tandem mass spectrometric assays. RESULTS: Our discovery integrating genomic and sphingolipidomic analysis identified leptin (Lep) and ceramide (Cer) (d18:1/25:0) as novel biomarkers for early gestational assessment of PE. Our longitudinal observation revealed a marked elevation of Lep/Cer (d18:1/25:0) ratio in maternal serum at a median of 23 weeks' gestation among women with impending PE as compared with women with uncomplicated pregnancy. The Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting impending event of PE with superior sensitivity (85% vs 20%) and area under curve (0.92 vs 0.52) from 5 to 25 weeks of gestation. CONCLUSIONS: Our study demonstrated the longitudinal measurement of maternal Lep/Cer (d18:1/25:0) ratio allows the non-invasive assessment of PE to identify pregnancy at high risk in early gestation, outperforming the established sFlt-1/PlGF ratio test.

Duke Scholars

Published In

BMJ Open

DOI

EISSN

2044-6055

Publication Date

November 25, 2021

Volume

11

Issue

11

Start / End Page

e050963

Location

England

Related Subject Headings

  • Retrospective Studies
  • Pregnancy
  • Predictive Value of Tests
  • Pre-Eclampsia
  • Placenta Growth Factor
  • Placenta
  • Leptin
  • Humans
  • Female
  • Ceramides
 

Citation

APA
Chicago
ICMJE
MLA
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Huang, Q., Hao, S., You, J., Yao, X., Li, Z., Schilling, J., … Ling, X. B. (2021). Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation. BMJ Open, 11(11), e050963. https://doi.org/10.1136/bmjopen-2021-050963
Huang, Qianyang, Shiying Hao, Jin You, Xiaoming Yao, Zhen Li, James Schilling, Sheeno Thyparambil, et al. “Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation.BMJ Open 11, no. 11 (November 25, 2021): e050963. https://doi.org/10.1136/bmjopen-2021-050963.
Huang Q, Hao S, You J, Yao X, Li Z, Schilling J, et al. Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation. BMJ Open. 2021 Nov 25;11(11):e050963.
Huang, Qianyang, et al. “Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation.BMJ Open, vol. 11, no. 11, Nov. 2021, p. e050963. Pubmed, doi:10.1136/bmjopen-2021-050963.
Huang Q, Hao S, You J, Yao X, Li Z, Schilling J, Thyparambil S, Liao W-L, Zhou X, Mo L, Ladella S, Davies-Balch SR, Zhao H, Fan D, Whitin JC, Cohen HJ, McElhinney DB, Wong RJ, Shaw GM, Stevenson DK, Sylvester KG, Ling XB. Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation. BMJ Open. 2021 Nov 25;11(11):e050963.

Published In

BMJ Open

DOI

EISSN

2044-6055

Publication Date

November 25, 2021

Volume

11

Issue

11

Start / End Page

e050963

Location

England

Related Subject Headings

  • Retrospective Studies
  • Pregnancy
  • Predictive Value of Tests
  • Pre-Eclampsia
  • Placenta Growth Factor
  • Placenta
  • Leptin
  • Humans
  • Female
  • Ceramides