Peculiarities of endothelial dysfunction humoral markers during the first month of life in premature infants depending on the severity of respiratory disorders

The role of vascular endothelial factors has been thoroughly studied in scientific publications; however, studies assessing the functional activity of the endothelium in premature infants, taking into account the severity of respiratory disorders, remain insufficient. Objective . To study concentrations of humoral markers of endothelial dysfunction in the umbilical cord blood of premature infants depending on the degree of respiratory distress during the first month of life. Materials and Methods . The study included 150 premature infants (28 ^0/7 –32 ^6/7 weeks of gestation) divided at birth into three groups according to the severity of respiratory disorders (Silverman-Andersen scale): Group 1 - 77 premature infants with severe respiratory disorders; Group 2 - 32 children with moderate respiratory disorders; Group 3 - 34 premature infants with initial signs of respiratory disorders. In the study groups, the concentration of endothelin 1 (ET-1), total nitrite and nitrate (NO₂^- and NO₃^–), vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-1 (sVEGF-R1) in umbilical cord blood was determined. Results . In children with moderate and severe respiratory disorders, the same type of changes was established at birth: an increase in the level of endothelin 1, total nitrite and nitrate. In children with severe respiratory failure, an increase in the concentration of endothelin-1 with a decrease in the content of endogenous nitrite, as well as an imbalance between angiogenesis factors (VEGF, sVEGF-R1), persisting up to 28–30 days of life. In children with moderate respiratory failure, endothelial dysfunction was determined immediately after birth, with the indicators returning to the values of children with initial signs of respiratory disorders by the end of the first month of life. Conclusion . The results obtained in this work make it possible to evaluate the predictive significance of the functional activity of the endothelium in the implementation of neonatal complications in premature infants with varying degrees of respiratory disorders.

1. Zav`yalov O.V., Ignatko I.V., Il`enko L.I., Pasechnik I.N. Silverman-Andersen scale in the assessment of respiratory distress syndrome of prematurity: clinical and prognostic significance. Akusherstvo, Ginekologiya i Reprodukciya (Оbstetrics, Gynecology and Reproduction). 2023; 17(3):357-365. (in Russ.) DOI: 10.17749/2313-7347/ob.gyn.rep.2023.403

2. N.N. Voldin (ed.) Guidelines for management of neonates with respiratory distress syndrome. Moscow: Rossiyskaya assotsiatsiya specialistov perinatal’noy meditsiny. pp. 16–3 (in Russ.).

3. Reiterer F., Schwaberger B., Freidl T., Schmölzer G., Pichler G., Urlesberger B. Lung-protective ventilatory strategies in intubated preterm neonates with RDS. Paediatr Respir Rev. 2017; 23:89-96. DOI: 10.1016/j.prrv.2016.10.007

4. Chen L., Xia H.F., Shang Y., Yao S.L. Molecular mechanisms of ventilator-induced lung injury. Chin Med J (Engl). 2018; 131(10):1225–1231. DOI: 10.4103/0366-6999.226840

5. Kuz’menko G.N., Nazarov S.B., Maly’shkina A.I., Popova I.G. The characteristics of function of endothelium in premature neonates with respiratory distress-syndrome. Klinicheskaya laboratornaya diagnostika (Russian Clinical Laboratory Diagnostic). 2016; 61(4):214-219. (in Russ.). DOI 10.18821/0869-2084-2016-61-4-214-219

6. Rajendran P., Rengarajan T., Thangavel J., Nishigaki Y., Sakthisekaran D., Sethi G. et al. The vascular endothelium and human diseases. Int J Biol Sci. 2013; 9(10):1057-1069. DOI: 10.7150/ijbs.7502. doi: 10.7150/ijbs.7502.

7. Morty R.E. Recent advances in the pathogenesis of BPD. Seminars in perina tology. 2018; 42(7):404–412. DOI:10.1053/j.semperi.2018.09.001

8. Shemia M.S. El, Tawfikb S., Khafagya S.M., Hamzac M.T. and Youssefa A.M.A. Endothelin 1 as a predictor marker for bronchopulmonary dysplasia in preterm neonates with respiratory distress syndrome Journal of Neonatal-Perinatal Medicine. 2017; 10(1):1-5. DOI:10.3233/NPM-1653

9. Pugach V.A., Tyunin M.A., Vlasov T.D., Il’inskij N.S., Gogolevskij A.S., Chepur S.V. Biomarkers of acute respiratory distress syndrome: problems and prospects of their application. Vestnik anesteziologii i reanimatologii (Messenger of anesthesiology and resuscitation). (in Russ.) DOI: 10.21292/2078-5658-2019-16-4-38-46

10. Sweetman D.U., Onwuneme C., Watson W.R., Murphy J.F., Molloy E.J. Perinatal Asphyxia and Erythropoietin and VEGF: Serial Serum and Cerebrospinal Fluid Responses. Neonatology. 2017; 111(3):253-259. DOI: 10.1159/000448702

11. O’Hare F.M., Watson R.W., O’Neill A., Segurado R., Sweetman D., Downey P., Mooney E., Murphy J., Donoghue V., Molloy E.J. Serial cytokine alterations and abnormal neuroimaging in newborn infants with encephalopathy. Acta Paediatr. 2017; 106(4):561-567. DOI: 10.1111/apa.13745

12. Silverman W.A., Andersen D.H. A сontrolled clinical trial of effects of water mist on obstructive respirato ry signs, death rate and necropsy findings among premature infants. Pediatrics. 1956; 17(1):1-10. PMID: 13353856

13. Mel’nikova Yu.S, Makarova T.P. Endothelial dysfunction as a central link in the pathogenesis of chronic diseases. Kazanskij medicinskij zhurnal (Kazan Med J) 2015; 96(4):659-665. (in Russ.) DOI: 10.17750/KMJ2015-659

14. Vassiliou A.G., Kotanidou A., Dimopoulou I., Orfanos S.E. Endothelial Damage in Acute Respiratory Distress Syndrome. Int J Mol Sci. 2020; 21(22):8793. DOI: 10.3390/ijms21228793

15. Levchenko L.A., Klimenko T.M., Xmelevskaya I.G. Mediators of endothelial dysfunction in preterm neonates with respiratory distress. «Chelovek i ego zdorov`e 2015; 2:34-40 (in Russ.).

16. Zakharova S.Yu., Levina L.G. Humoral markers of endothelial dysfunction in first-year-old children born with intrauterine growth restriction syndrome. Rossiyskiy vestnik perinatologii i pediatrii (Russian Bulletin of Perinatology and Pediatrics) 2019; 64(6):57-61. (in Russ.) DOI:10.21508/1027-4065-2019-64-6-57-61.

17. Golosnaya G.S., Krasnoruckaya O.N., Ermolenko N.A., Kholichev D.A., Ogurtsev A.V. Results of enzyme-linked immunosorbent assay of vasculature endothelial growth factor (VEGF) in blood serum of preterm neonates with perinatal hypoxic brain damage. Russkiy zhurnal detskoy nevrologii 2023; 18(2-3):38-44. (in Russ.). DOI:10.17650/2073-8803-2023-18-2-3-38-44

18. Gladkova K.A., Sakalo V.A., Vtorushina V.V., Piskulina A.A., Frolova E.R., Kostyukov K.V., Khodzhaeva Z.S. Role of vasculogenesis and angiogenesis factors in selective fetal growth restriction in monochorionic multiple pregnancies. Akusherstvo i ginekologiya (Obstetrics and Gynecology) 2023; 1:48-54. DOI: 10.18565/aig.2022.278