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

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 th...

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Autores principales: Huang, Qianyang, Hao, Shiying, You, Jin, Yao, Xiaoming, Li, Zhen, Schilling, James, Thyparambil, Sheeno, Liao, Wei-Li, Zhou, Xin, Mo, Lihong, Ladella, Subhashini, Davies-Balch, Shantay R, Zhao, Hangyi, Fan, David, Whitin, John C, Cohen, Harvey J, McElhinney, Doff B, Wong, Ronald J, Shaw, Gary M, Stevenson, David K, Sylvester, Karl G, Ling, Xuefeng B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627403/
https://www.ncbi.nlm.nih.gov/pubmed/34824115
http://dx.doi.org/10.1136/bmjopen-2021-050963
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author Huang, Qianyang
Hao, Shiying
You, Jin
Yao, Xiaoming
Li, Zhen
Schilling, James
Thyparambil, Sheeno
Liao, Wei-Li
Zhou, Xin
Mo, Lihong
Ladella, Subhashini
Davies-Balch, Shantay R
Zhao, Hangyi
Fan, David
Whitin, John C
Cohen, Harvey J
McElhinney, Doff B
Wong, Ronald J
Shaw, Gary M
Stevenson, David K
Sylvester, Karl G
Ling, Xuefeng B
author_facet Huang, Qianyang
Hao, Shiying
You, Jin
Yao, Xiaoming
Li, Zhen
Schilling, James
Thyparambil, Sheeno
Liao, Wei-Li
Zhou, Xin
Mo, Lihong
Ladella, Subhashini
Davies-Balch, Shantay R
Zhao, Hangyi
Fan, David
Whitin, John C
Cohen, Harvey J
McElhinney, Doff B
Wong, Ronald J
Shaw, Gary M
Stevenson, David K
Sylvester, Karl G
Ling, Xuefeng B
author_sort Huang, Qianyang
collection PubMed
description 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.
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spelling pubmed-86274032021-12-10 Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation Huang, Qianyang Hao, Shiying You, Jin Yao, Xiaoming Li, Zhen Schilling, James Thyparambil, Sheeno Liao, Wei-Li Zhou, Xin Mo, Lihong Ladella, Subhashini Davies-Balch, Shantay R Zhao, Hangyi Fan, David Whitin, John C Cohen, Harvey J McElhinney, Doff B Wong, Ronald J Shaw, Gary M Stevenson, David K Sylvester, Karl G Ling, Xuefeng B BMJ Open Obstetrics and Gynaecology 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. BMJ Publishing Group 2021-11-24 /pmc/articles/PMC8627403/ /pubmed/34824115 http://dx.doi.org/10.1136/bmjopen-2021-050963 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Obstetrics and Gynaecology
Huang, Qianyang
Hao, Shiying
You, Jin
Yao, Xiaoming
Li, Zhen
Schilling, James
Thyparambil, Sheeno
Liao, Wei-Li
Zhou, Xin
Mo, Lihong
Ladella, Subhashini
Davies-Balch, Shantay R
Zhao, Hangyi
Fan, David
Whitin, John C
Cohen, Harvey J
McElhinney, Doff B
Wong, Ronald J
Shaw, Gary M
Stevenson, David K
Sylvester, Karl G
Ling, Xuefeng B
Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation
title Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation
title_full Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation
title_fullStr Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation
title_full_unstemmed Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation
title_short Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation
title_sort early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation
topic Obstetrics and Gynaecology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627403/
https://www.ncbi.nlm.nih.gov/pubmed/34824115
http://dx.doi.org/10.1136/bmjopen-2021-050963
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