The levels of oxidative stress markers in maternal and umbilical cord blood of pregnant women with diabetes mellitus in terms of blood flow redistribution in the fetal venous system
Zalozniaia I.V., Kopteeva E.V., Milyutina Yu.P., Korenevsky A.V., Arutjunyan A.V., Shelaeva E.V., Kapustin R.V., Kogan I.Yu.
Oxidative stress is a significant contributing factor in the development of congenital anomalies, morbidity, and mortality in newborns during pregnancies complicated by diabetes mellitus. Alterations in the antioxidant system that occur during this process, along with transformations of the fetal venous circulation, represent crucial adaptive mechanisms of the developing organism to adverse conditions in the intrauterine environment.
Objective: To examine the levels of oxidative stress markers in pregnant women with pregestational diabetes mellitus (type 1 or 2 diabetes mellitus) in relation to the redistribution of blood flow in the fetal venous system, compared to a control group.
Materials and methods: A prospective study was conducted in the D.O. Ott Research Institute for OG&R from February 2022 to September 2023. The study included 70 women divided into the following groups: Group I included pregnant women with pregestational diabetes mellitus and a ductus venosus shunt fraction ≤16.5% (n=22); Group II included women with pregestational diabetes mellitus and a ductus venosus shunt fraction >16.5% (n=24); and Group III, the control group (n=24). The levels of 3-nitrotyrosine, malondialdehyde, catalase activity, and total antiradical activity were determined in maternal and cord blood serum at 37–41 weeks of pregnancy. Ultrasound examination was also performed to assess venous hemodynamics in the vessels of the umbilical portal venous system of the fetus.
Results: The threshold level for the redistribution of highly oxygenated blood in the ductus venosus to the fetal brain and heart was 16.5%. Analysis of oxidative stress markers in patients with pregestational diabetes mellitus based on the shunt fraction in the ductus venosus showed a significant increase in the levels of 3-nitrotyrosine and malondialdehyde in the group with a reduced shunt fraction in the ductus venosus (≤16.5%) compared to the control group and the group of women with a normal shunt fraction in the ductus venosus (>16.5%). The levels of catalase and antiradical activity were significantly increased in women in the group with a normal shunt fraction in the ductus venosus and remained unchanged compared to the control group in the group with a reduced fraction.
Conclusion: The study results indicate that oxidative stress is induced in patients with pregestational diabetes mellitus, accompanied by a decrease in the shunt fraction in the ductus venosus. This associated change reflects a violation of the compensatory capabilities of the fetus, aimed primarily at preserving the structure and function of the newborn brain. This may underlie the pathogenesis of irreversible changes in the formation and development of the fetal nervous system during pregnancy complicated by diabetes mellitus.
Authors' contributions: All authors made a significant contribution to the conceptualization, execution and preparation of the study, read and approved the final version prior to submission. Zalozniaia I.V. – material collection and processing, drafting of the manuscript, Kopteeva E.V. – material collection and processing, statistical analysis, conception and design of the study, Milyutina Yu.P., Shelaeva E.V. – material collection and processing, Korenevsky A.V., Arutjunyan A.V. – editing of the manuscript, Kapustin R.V., Kogan I.Yu. – conception and design of the study.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: The study was conducted in accordance with the research theme for the 2022–2024 “Optimization of methods for prediction, prevention and treatment of “great obstetric syndromes”, as well as delivery strategies in pregnant women from high-risk groups, in order to improve obstetric and perinatal outcomes” (state registration number 1021062812133-0 3.2.2).
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the D.O. Ott Research Institute for OG&R (Ref. No: 115 of 03.02.2022).
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Zalozniaia I.V., Kopteeva E.V., Milyutina Yu.P., Korenevsky A.V., Arutjunyan A.V., Shelaeva E.V.,
Kapustin R.V., Kogan I.Yu. The levels of oxidative stress markers in maternal and umbilical cord blood
of pregnant women with diabetes mellitus in terms of blood flow redistribution in the fetal venous system.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (10): 41-51 (in Russian)
https://dx.doi.org/10.18565/aig.2024.178
Keywords
diabetes mellitus
gestational diabetes mellitus
pregnancy
oxidative stress
nitrotyrosine
malondialdehyde
catalase
total antiradical activity
NRF2
ductus venosus
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Received 22.07.2024
Accepted 24.09.2024
About the Authors
Irina V. Zalozniaia, PhD (Bio), D.O. Ott Research Institute for OG&R, 3 Mendeleevskaya Line, Saint Petersburg, 199034, Russia, irinabiolog2012@yandex.ru,eLibrary SPIN: 2488-3790, https://orcid.org/0000-0002-0576-9690
Ekaterina V. Kopteeva, MD, D.O. Ott Research Institute for OG&R, 3 Mendeleevskaya Line, Saint Petersburg, 199034, Russia, ekaterina_kopteeva@bk.ru,
eLibrary SPIN: 9421-6407, https://orcid.org/0000-0002-9328-8909
Yulia P. Milyutina, PhD (Bio), D.O. Ott Research Institute for OG&R, 3 Mendeleevskaya Line, Saint Petersburg, 199034, Russia, milyutina1010@mail.ru,
eLibrary SPIN: 6449-5635, https://orcid.org/0000-0003-1951-8312
Andrey V. Korenevsky, Dr. Bio. Sci., D.O. Ott Research Institute for OG&R, 3 Mendeleevskaya Line, Saint Petersburg, 199034, Russia, a.korenevsky@yandex.ru,
eLibrary SPIN: 7942-6016, https://orcid.org/0000-0002-0365-8532
Alexander V. Arutjunyan, Dr. Bio. Sci., Professor, D.O. Ott Research Institute for OG&R, 3 Mendeleevskaya Line, Saint Petersburg, 199034, Russia, alexarutiunjan@gmail.com, eLibrary 9938-5277, https://orcid.org/0000-0002-0608-9427
Elizaveta V. Shelaeva, PhD, D.O. Ott Research Institute for OG&R, 3 Mendeleevskaya Line, Saint Petersburg, 199034, Russia, eshelaeva@yandex.ru, eLibrary SPIN: 7440-0555, https://orcid.org/0000-0002-9608-467X
Roman V. Kapustin, Dr. Med. Sci., D.O. Ott Research Institute for OG&R, 3 Mendeleevskaya Line, Saint Petersburg, 199034, Russia, kapustin.roman@gmail.com,
eLibrary SPIN: 7300-6260, https://orcid.org/0000-0002-2783-3032
Igor Yu. Kogan, Dr. Med. Sci., Professor, Corresponding Member of the Russian Academy of Sciences, D.O. Ott Research Institute for OG&R, 3 Mendeleevskaya Line,
Saint Petersburg, 199034, Russia, ikogan@mail.ru, eLibrary SPIN: 6572-6450, https://orcid.org/0000-0002-7351-6900
Corresponding author: Irina V. Zalozniaia, irinabiolog2012@yandex.ru
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