The Metabolic Signatures of Surviving Cotwins in Cases of Single Intrauterine Fetal Death During Monochorionic Diamniotic Pregnancy: A Prospective Case-Control Study

Introduction: Single intrauterine fetal death (sIUFD) in monochorionic diamniotic (MCDA) twin pregnancy may be associated with adverse clinical outcomes and possible metabolic changes in the surviving co-twin. Metabolomic profiling has not been undertaken before in these complex twin pregnancies.Met...

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Main Authors: Xiyao Liu, Huijia Fu, Li Wen, Fangyu Zhu, Yue Wu, Zhi Chen, Richard Saffery, Chang Chen, Hongbo Qi, Chao Tong, Philip N. Baker, Mark D. Kilby
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2022.799902/full
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author Xiyao Liu
Xiyao Liu
Huijia Fu
Huijia Fu
Huijia Fu
Li Wen
Li Wen
Fangyu Zhu
Fangyu Zhu
Yue Wu
Yue Wu
Zhi Chen
Zhi Chen
Richard Saffery
Chang Chen
Hongbo Qi
Hongbo Qi
Hongbo Qi
Chao Tong
Chao Tong
Philip N. Baker
Philip N. Baker
Mark D. Kilby
Mark D. Kilby
author_facet Xiyao Liu
Xiyao Liu
Huijia Fu
Huijia Fu
Huijia Fu
Li Wen
Li Wen
Fangyu Zhu
Fangyu Zhu
Yue Wu
Yue Wu
Zhi Chen
Zhi Chen
Richard Saffery
Chang Chen
Hongbo Qi
Hongbo Qi
Hongbo Qi
Chao Tong
Chao Tong
Philip N. Baker
Philip N. Baker
Mark D. Kilby
Mark D. Kilby
author_sort Xiyao Liu
collection DOAJ
description Introduction: Single intrauterine fetal death (sIUFD) in monochorionic diamniotic (MCDA) twin pregnancy may be associated with adverse clinical outcomes and possible metabolic changes in the surviving co-twin. Metabolomic profiling has not been undertaken before in these complex twin pregnancies.Methods: In this prospectively collected case-control study, three cross-cohort comparisons were made between sIUFD MCDA (n = 16), uncomplicated MCDA (n = 16, eight pairs), and uncomplicated singleton pregnancies (n = 8). To identify major sources of variation within the sIUFD MCDA cohort, a secondary comparison was conducted between spontaneous sIUFD (n = 8) and sIUFD in MCDA twins due to selective termination of a single abnormal fetus by radiofrequency ablation (RFA) (n = 8). Metabolomics analysis of placental tissue and umbilical cord plasma was performed using LC-MS profiling. The underlying metabolic networks and pathways were analyzed by web-based platforms. Associations and statistical correlations of all identified differential metabolites with neonatal birthweight and birth length were assessed by multivariable linear regression, adjusted for maternal age and gestation.Results: Across four comparisons, 131 and 111 differential metabolites were identified in placental tissue and cord plasma, respectively, with the highest variation seen between the spontaneous vs. single-induced IUFD in MCDA twins by RFA in the cord plasma. Conversely, the number of viable fetuses and the presence of sIUFD in MCDA twins had the highest impact on metabolite variation in placental tissue. Compounds correlated with fetal growth including placental acylcarnitines and gangliosides, along with specific amino acids (e.g., histidinyl-hydroxyproline), xenobiotics and biliverdin in cord plasma.Conclusion: sIUFD in MCDA twin pregnancy correlates with distinctive metabolic signatures, mostly in fatty acyls and complex lipids, in placental tissue and cord plasma of the surviving cotwin. Some metabolites are also associated with fetal growth.
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spelling doaj.art-05405bb8081b4911b9a4e090ade2256a2022-12-22T02:49:14ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-04-01910.3389/fmolb.2022.799902799902The Metabolic Signatures of Surviving Cotwins in Cases of Single Intrauterine Fetal Death During Monochorionic Diamniotic Pregnancy: A Prospective Case-Control StudyXiyao Liu0Xiyao Liu1Huijia Fu2Huijia Fu3Huijia Fu4Li Wen5Li Wen6Fangyu Zhu7Fangyu Zhu8Yue Wu9Yue Wu10Zhi Chen11Zhi Chen12Richard Saffery13Chang Chen14Hongbo Qi15Hongbo Qi16Hongbo Qi17Chao Tong18Chao Tong19Philip N. Baker20Philip N. Baker21Mark D. Kilby22Mark D. Kilby23State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, ChinaInternational Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, ChinaInternational Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaDepartment of Reproductive Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, ChinaInternational Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, ChinaInternational Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, ChinaInternational Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, ChinaInternational Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaMolecular Immunity, Murdoch Children’s Research Institute, Parkville, VIC, AustraliaInstitute of Life Sciences, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, ChinaInternational Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaChongqing Women and Children’s Health Center, Chongqing, ChinaState Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, ChinaInternational Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaInternational Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaCollege of Life Sciences, University of Leicester, Leicester, United KingdomCollege of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomFetal Medicine Centre, Birmingham Women’s and Children’s Foundation Trust, Birmingham, United KingdomIntroduction: Single intrauterine fetal death (sIUFD) in monochorionic diamniotic (MCDA) twin pregnancy may be associated with adverse clinical outcomes and possible metabolic changes in the surviving co-twin. Metabolomic profiling has not been undertaken before in these complex twin pregnancies.Methods: In this prospectively collected case-control study, three cross-cohort comparisons were made between sIUFD MCDA (n = 16), uncomplicated MCDA (n = 16, eight pairs), and uncomplicated singleton pregnancies (n = 8). To identify major sources of variation within the sIUFD MCDA cohort, a secondary comparison was conducted between spontaneous sIUFD (n = 8) and sIUFD in MCDA twins due to selective termination of a single abnormal fetus by radiofrequency ablation (RFA) (n = 8). Metabolomics analysis of placental tissue and umbilical cord plasma was performed using LC-MS profiling. The underlying metabolic networks and pathways were analyzed by web-based platforms. Associations and statistical correlations of all identified differential metabolites with neonatal birthweight and birth length were assessed by multivariable linear regression, adjusted for maternal age and gestation.Results: Across four comparisons, 131 and 111 differential metabolites were identified in placental tissue and cord plasma, respectively, with the highest variation seen between the spontaneous vs. single-induced IUFD in MCDA twins by RFA in the cord plasma. Conversely, the number of viable fetuses and the presence of sIUFD in MCDA twins had the highest impact on metabolite variation in placental tissue. Compounds correlated with fetal growth including placental acylcarnitines and gangliosides, along with specific amino acids (e.g., histidinyl-hydroxyproline), xenobiotics and biliverdin in cord plasma.Conclusion: sIUFD in MCDA twin pregnancy correlates with distinctive metabolic signatures, mostly in fatty acyls and complex lipids, in placental tissue and cord plasma of the surviving cotwin. Some metabolites are also associated with fetal growth.https://www.frontiersin.org/articles/10.3389/fmolb.2022.799902/fullLC-MSmaternal-fetal interfacemetabolitesmetabolomeradiofrequency ablationspontaneous fetal death
spellingShingle Xiyao Liu
Xiyao Liu
Huijia Fu
Huijia Fu
Huijia Fu
Li Wen
Li Wen
Fangyu Zhu
Fangyu Zhu
Yue Wu
Yue Wu
Zhi Chen
Zhi Chen
Richard Saffery
Chang Chen
Hongbo Qi
Hongbo Qi
Hongbo Qi
Chao Tong
Chao Tong
Philip N. Baker
Philip N. Baker
Mark D. Kilby
Mark D. Kilby
The Metabolic Signatures of Surviving Cotwins in Cases of Single Intrauterine Fetal Death During Monochorionic Diamniotic Pregnancy: A Prospective Case-Control Study
Frontiers in Molecular Biosciences
LC-MS
maternal-fetal interface
metabolites
metabolome
radiofrequency ablation
spontaneous fetal death
title The Metabolic Signatures of Surviving Cotwins in Cases of Single Intrauterine Fetal Death During Monochorionic Diamniotic Pregnancy: A Prospective Case-Control Study
title_full The Metabolic Signatures of Surviving Cotwins in Cases of Single Intrauterine Fetal Death During Monochorionic Diamniotic Pregnancy: A Prospective Case-Control Study
title_fullStr The Metabolic Signatures of Surviving Cotwins in Cases of Single Intrauterine Fetal Death During Monochorionic Diamniotic Pregnancy: A Prospective Case-Control Study
title_full_unstemmed The Metabolic Signatures of Surviving Cotwins in Cases of Single Intrauterine Fetal Death During Monochorionic Diamniotic Pregnancy: A Prospective Case-Control Study
title_short The Metabolic Signatures of Surviving Cotwins in Cases of Single Intrauterine Fetal Death During Monochorionic Diamniotic Pregnancy: A Prospective Case-Control Study
title_sort metabolic signatures of surviving cotwins in cases of single intrauterine fetal death during monochorionic diamniotic pregnancy a prospective case control study
topic LC-MS
maternal-fetal interface
metabolites
metabolome
radiofrequency ablation
spontaneous fetal death
url https://www.frontiersin.org/articles/10.3389/fmolb.2022.799902/full
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