Personalised medicine in action: lipidomic markers for predicting premature rupture of membranes

DOI

https://dx.doi.org/10.18565/aig.2024.334

Baisova A.R., Amiraslanov E.Yu., Frankevich V.E., Chagovets V.V., Tokareva A.O., Tyutyunnik V.L.
1) Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia; 2) Siberian State Medical University, Ministry of Health of Russia, Tomsk, Russia

Objective: Assessment of lipid profile in pregnant women to identify biomarkers that have prognostic potential in premature rupture of membranes (PROM).
Materials and methods: The prospective case-control study included 110 pregnant women. The group with preterm labor and PROM was comprised of 30 women, and the control group included 80 women. Plasma lipid extracts were analyzed using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Lipids were identified using LipidMatch R-script based on exact mass using the LIPID MAPS Structure Database (LMSD) and tandem mass spectrometry (MS/MS).
Results: A total of 141 maternal plasma lipids including cholesteryl esters, ceramides, monogalactosyldiacylglycerols, lysophosphatidylcholines, ether-linked phosphatidylcholines, phosphatidylinositols, phosphatidylglycerols, oxidized lipids, and triacylglycerols were detected in positive and negative ion modes. Comparative analysis of plasma in patients in the control group and in the group with premature rupture of membranes before 37 weeks of gestation showed statistically significant changes (p<0.05) in 34 lipids. Based on analysis of different expression of lipids that demonstrated statistically significant correlation with clinical data according to the Spearman’s correlation, the model was developed to predict PROM before 37 weeks of gestation with sensitivity of 97.3% and specificity of 97.4%. The area under the curve (AUC) was 0.994 and the cut-off value was 0.5.
Conclusion: Metabolomic plasma profile changes in lipids, such as ceramides, monogalactosyldiacylglycerols, lysophosphatidylcholines, ether-linked phosphatidylcholines, phosphatidylinositols, phosphatidylglycerols, oxidized lipids and triacylglycerols correlate with the risk of developing PROM. Lysophosphatidylcholines (LPC, LPE) can be considered to be early markers of proinflammatory activation. The prognostic model based on analysis of plasma lipid profile opens perspectives in the improvement of preventive measures against PROM, and also contributes to the improvement of perinatal outcomes both in mothers and newborns.

Authors' contributions: Baisova A.R. – development of the study design, obtaining data for analysis, collecting biological materials for the study, drafting the manuscript, Amiraslanov E.Yu. – development of the study design, review of publications on the topic of the article, analysis of the obtained data, writing the text of the manuscript; Chagovets V.V. – conducting metabolomic analysis using mass spectrometry, statistical analysis; Tokareva A.O. – statistical data analysis; Amiraslanov E.Yu., Frankevich V.E., Chagovets V.V., Tyutyunnik V.L. – manuscript editing.
Conflicts of interest: The authors confirm that they have no conflicts of interest to declare.
Funding: The study was supported by Russian Science Foundation grant No. 24-64-00006 (https://rscf.ru/project/24-64-00006/).
Ethical Approval: The study was approved by the local Ethics Committee of the Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia (Protocol No. 11 of November 11, 2021).
Patient Consent for Publication: The patients have signed informed consent for participation in the study and publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Baisova A.R., Amiraslanov E.Yu., Frankevich V.E., Chagovets V.V., Tokareva A.O., Tyutyunnik V.L. Personalised medicine in action: lipidomic markers for predicting premature rupture of membranes.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (1): 55-65 (in Russian)
https://dx.doi.org/10.18565/aig.2024.334

premature rupture of membranes

preterm labor

lipid profile

lipidomics

prognostic markers

mass spectrometry

Full text (in Russian)

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Received 27.12.2024

Accepted 21.01.2025

Almira R. Baisova, PhD student, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, almira.baisova@mail.ru, https://orcid.org/0009-0004-4546-2388
Elrad Yu. Amiraslanov, PhD, Head of the Department of Obstetrics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, eldis@mail.ru, https://orcid.org/0000-0001-5601-1241
Vladimir E Frankevich, Dr. Sci. (in Physics and Mathematics), Head of Department of Systems Biology in Reproduction, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4; Leading Researcher at the Laboratory
of Translational Medicine, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moskovsky tract, 2, v_frankevich@oparina4.ru,
https://orcid.org/0000-0002-9780-4579
Vitaliy V. Chagovets, PhD, Senior Researcher at the Proteomics of Human Reproduction Department, Academician V.I. Kulakov National Medical Research Center
for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, v_chagovets@oparina4.ru,
https://orcid.org/0000-0002-5120-376X
Alisa O. Tokareva, PhD, Specialist at the Laboratory of Clinical Proteomics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, alisa.tokareva@phystech.edu, https://orcid.org/0000-0001-5918-9045
Victor L. Tyutyunnik, Professor, Dr. Med. Sci., Leading Researcher at the Center for Scientific and Clinical Research, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, tioutiounnik@mail.ru,
Researcher ID: B-2364-2015, SPIN: 1963-1359, Authors ID: 213217, Scopus Author ID: 56190621500, https://orcid.org/0000-0002-5830-5099

Personalised medicine in action: lipidomic markers for predicting premature rupture of membranes

Baisova A.R., Amiraslanov E.Yu., Frankevich V.E., Chagovets V.V., Tokareva A.O., Tyutyunnik V.L.

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