The metabolic signatures of surviving cotwins in cases of single intrauterine fetal death during monochorionic diamniotic pregnancy: A prospective case-control study

Liu, Xiyao, Fu, Huijia, Wen, Li, Zhu, Fangyu, Wu, Yue, Chen, Zhi, Saffery, Richard, Chen, Chang, Qi, Hongbo, Tong, Chao, Baker, Philip N. and Kilby, Mark D. (2022) 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, 9. ISSN 2296-889X

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Abstract

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.

Item Type: Article
Additional Information: Data Availability Statement: The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors. Funding Information: This work is supported by the National Natural Science Foundation of China (U21A20346, 81520108013, 81871189, 82071675, 82001580 and 82171662), Chongqing Science and Technology Commission (cstc2021ycjh-bgzxm0192), Chongqing Health Committee (2019GDRC012) Chongqing Education Commission (KJZD-K202100404). The sponsors had no role in the study design; data collection, analysis and interpretation of data; writing of the report; or decision to submit the article for publication.
Uncontrolled Keywords: lc-ms,maternal-fetal interface,metabolites,metabolome,radiofrequency ablation,spontaneous fetal death,biochemistry,molecular biology,biochemistry, genetics and molecular biology (miscellaneous) ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 07 May 2025 16:30
Last Modified: 09 May 2025 09:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/99203
DOI: 10.3389/fmolb.2022.799902

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