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Obstetrics and Gynegology2024№4
Diagnostic significance of proteome analysis...

Diagnostic significance of proteome analysis of maternal plasma in fetal growth restriction

DOI
https://dx.doi.org/10.18565/aig.2023.299

Volochaeva M.V., Tokareva A.O., Kononikhin A.S., Kukaev E.N., Tyutyunnik V.L., Kan N.E., Starodubtseva N.L.

1) Academician V.I. Kulakov National Medical Research Centre of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia; 2) Skolkovo Institute of Science and Technology, Moscow, Russia; 3) V.L. Talrose Institute for Energy Problems of Chemical Physics, N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Moscow, Russia

Objective: The objective of the study was to determine diagnostic criteria for fetal growth restriction based on quantitative proteome analysis of maternal blood plasma.
Materials and methods: Case-control study included 50 pregnant women, who were into 5 groups. Group I consisted of pregnant women with early fetal growth restriction (<32 weeks) (n=10). Group II included pregnant women with late fetal growth restriction (≥32 weeks) (n=10). Group III and IV comprised the patients, who delivered before and after 32 weeks (n=10/n=10), respectively. Group V included pregnant women with small for gestational age fetuses (≥32 weeks) (n=10). Postnatal assessment of growth and weight parameters in newborns (n=50) was conducted according to INTERGROWTH-21st charts to confirm the antenatal diagnosis of fetal growth restriction and small for gestational age newborns, as well as to determine the normal body weight in the group of women with preterm birth (before and after 32 weeks). Quantitative analysis of 125 plasma proteins was performed using BAK 125 Human Plasma Proteomics Kit (MRM Proteomics Inc., Montreal, Canada) by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Diagnostic models for fetal growth restriction and small for gestational age fetuses using logistic regression were developed after preliminary data processing.
Results: Based on the results of quantitative proteome analysis of maternal plasma proteins, three diagnostic models were developed. Model «1» (AUC=0.86), including alpha-2-macroglobulin as a variable, with 90% sensitivity and 90% specificity, enables to make the diagnosis of early fetal growth restriction. Model «2» (AUC=0.88), including the variables of proteins alpha-2-macroglobulin and apolipoprotein A-IV with 90% sensitivity and 80% specificity, enables to make the diagnosis of late fetal growth restriction. Model «3» (AUC=0.80), based on the variables of antithrombin-III and apolipoprotein C-I with 80% sensitivity and 80% specificity, enables to make the differential diagnosis of late fetal growth restriction and small for gestational age fetus.
Conclusion: The results of this study can be used in new approaches to diagnostic methods for different types of fetal growth restriction and small for gestational age fetus, as well as can be a starting point of future researches including potential therapeutic targets.

Authors' contributions: Volochaeva M.V., Tokareva A.O., Kononikhin A.S., Kukaev E.N., Tyutyunnik V.L., Kan N.E., Starodubtseva N.L. – the concept and design of the study, data collection and analysis, statistical data processing, writing the text of the manuscript, article editing.
Conflicts of interest: The authors have no conflicts of interest to declare. 
Funding: The work was carried out as part of experimental research «Improving management strategy and the timing of delivery for pregnant women with fetal growth restriction based on molecular genetic and metabolomic factors with subsequent introduction of modern diagnostic methods for the severity of this gestational complication», 121040600408-4.
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.
Patient Consent for Publication: The patients signed informed consent for 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: Volochaeva M.V., Tokareva A.O., Kononikhin A.S., Kukaev E.N., Tyutyunnik V.L., Kan N.E., 
Starodubtseva N.L. Diagnostic significance of proteome analysis of maternal plasma in fetal growth restriction.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (4): 59-68 (in Russian)
https://dx.doi.org/10.18565/aig.2023.299

Keywords

intrauterine growth restriction
diagnosis
quantitative proteome analysis
small-for-gestational-age fetus
Full text (in Russian)

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Received 22.12.2023

Accepted 20.03.2024

About the Authors

Maria V. Volochaeva, PhD, Senior Researcher, Department of Regional Cooperation and Integration; Physician, 1 Maternity 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, +7(919)968-72-98, volochaeva.m@yandex.ru, https://orcid.org/0000-0001-8953-7952
Alisa O. Tokareva, PhD, specialist, 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, +7(495)531-44-44 (доб. 3113), alisa.tokareva@phystech.edu,
https://orcid.org/0000-0001-5918-9045
Alexey S. Kononikhin, PhD, Senior Researcher, Laboratory of Clinical Proteomics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russia, 117997, Russia, Moscow, Ac. Oparina str., 4; Senior Researcher, Laboratory of Mass Spectrometry, Skolkovo Institute
of Science and Technology, +7(495)531-44-44 (доб. 3113), a_kononihin@oparina4.ru, https://orcid.org/0000-0002-2238-3458
Evgenii N. Kukaev, PhD, Senior Researcher, 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; Researcher, Semenov Research Center of Chemical Physics,
+7(495)531-44-44 (доб. 3113), e_kukaev@oparina4.ru, https://orcid.org/0000-0002-8397-3574
Victor L. Tyutyunnik, Professor, Dr. Med. Sci., Leading Researcher of 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, +7(903)969-50-41, tioutiounnik@mail.ru,
Researcher ID: B-2364-2015, SPIN-код: 1963-1359, Authors ID: 213217, Scopus Author ID: 56190621500, https://orcid.org/0000-0002-5830-5099
Natalia E. Kan, Professor, Dr. Med. Sci., Deputy Director of Science, 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, +7(926)220-86-55, kan-med@mail.ru, Researcher ID: B-2370-2015, SPIN-код:
5378-8437, Authors ID: 624900, Scopus Author ID: 57008835600, https://orcid.org/0000-0001-5087-5946
Natalia L. Starodubtseva, PhD, Head of 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, +7(495)531-44-44 (доб. 3113), n_starodubtseva@oparina4.ru,
https://orcid.org/0000-0001-6650-5915
Corresponding author: Maria V. Volochaeva, volochaeva.m@yandex.ru

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