The purpose of the monograph, which contains a modern view of the problem of adaptation of children with extremely low body weight, is to provide a wide range of doctors with basic information about the clinical picture, functional activity of innate and adaptive immunity, prognostic criteria of postnatal pathology, based on their own research. The specific features of the immunological reactivity of premature infants of various gestational ages who have developed bronchopulmonary dysplasia (BPD) and retinopathy of newborns (RN) from the moment of birth and after reaching postconceptional age (37-40 weeks) are described separately. The mechanisms of their implementation with the participation of factors of innate and adaptive immunity are considered in detail. Methods for early prediction of BPD and RN with the determination of an integral indicator and an algorithm for the management of premature infants with a high risk of postnatal complications at the stage of early rehabilitation are proposed. The information provided makes it possible to personify the treatment, preventive and rehabilitation measures in premature babies. The monograph is intended for obstetricians-gynecologists, neonatologists, pediatricians, allergists-immunologists, doctors of other specialties, residents, students of the system of continuing medical education. This work was done with financial support from the Ministry of Education and Science, grant of the President of the Russian Federation No. MK-1140.2020.7.
Children, extremely low body mass, neonatal pathology, immune system, weight, immunity, postnatal pathology, newborns
The birth of deeply premature babies with extremely low body weight (ELBW) is the most topical issue in modern perinatology due to the high risk of morbidity and mortality, despite the fact that the proportion of births with a gestational age of less than 32 weeks, as a rule, does not exceed 1.5- 2% [1, 2, 3, 4, 5]. According to foreign sources, the survival rate of this category of children over the past twenty years has significantly increased from 42 to 76% [6]. In recent years, there has been a decrease in the proportion of severe complications in children with EBMT against the background of improving organizational and medical technologies for nursing deeply premature babies, the quality of prenatal follow-up [7, 8]. However, the rates of chronic pathology and disability do not show a significant downward trend and remain high even in developed countries [9, 10, 11]. Functional immaturity of the respiratory, cardiovascular, immune, and central nervous systems (CNS) is prevalent among deeply premature newborns, which leads to a high susceptibility of children to the development of pathological conditions and is the cause of a high level of morbidity [12]. Undoubtedly, the improvement of methods of primary resuscitation care and respiratory support (sparing modes of artificial lung ventilation, preference for non-invasive ventilation with a decrease in oxygenation parameters), early use of a surfactant, improvement of neonatal care technologies, significantly improved prognosis of long-term postnatal use of corticosteroids 13, 14, 15, 16]. The child's immune system plays a leading role in the pathogenesis, clinical course and outcome of hypoxic and infectious diseases, which largely determines the possibility of full rehabilitation of premature babies [17, 18]. In recent years, the role of the cytokine cascade has been actively studied in the development of pathology of the perinatal period. The theory of imbalance of pro- and anti-inflammatory cytokines is considered both in the pathogenesis of the infectious process [18, 19, 20] and in non-infectious post-hypoxic conditions [21, 22]. A large part of scientific research is devoted to assessing the state of adaptive immunity [23, 24], while data on the functioning of the innate link of immunity are presented fragmentarily. However, it is the immunocompetent cells of inborn immunity that are the main ones in the formation of protection against bacterial complications and the formation of immune dysfunction. In connection with the peculiarities of the immunological resistance of children with EBMT, the leading cause of death along with serious injuries of the CNS are infectious and inflammatory diseases [25]. In modern works, much attention is paid to the stage of nursing children with EBMT in the conditions of the intensive care unit [23, 26]. However, there are few works devoted to the study of this category of children at the stage of early rehabilitation, taking into account the characteristics of inborn and adaptive immunity at the systemic and local levels, 8 Chistyakova G.N., Ustyantseva L.S., Remizova I.I., Ryumin V.E., Bychkova S.V. depending on the gestational age. Against the background of a deficiency of humoral protection factors, markers of nonspecific resistance, insufficiency of inborn and adaptive immunity, increased infectious morbidity in children with EBMT, it is important to study the mechanisms of development of postnatal complications from the standpoint of clinical and immunological adaptation of a premature baby, which was the purpose of writing this monograph.
1. Ailamazyan E. K. Controversial problems of premature birth and nursing children with extremely low weight / E. K. Ailamazyan, I. I. Evsyukova // Journal of obstetrics and women's diseases. - 2011. - No. 3. - P.183-189.
2. Albitsky V.Yu. Neonatal Mortality with Extreme Low Birth Weight /Albitsky V.Yu., E.N. Baybarina, Z.Kh. Sorokin et al. // Public health and health care. - 2010. - No. 2. - P. 16-21.
3. Baybarina E.N. Outcomes of pregnancy in the period of 22-27 weeks in medical institutions of the Russian Federation / E. N.Baybarina, Z. Kh. Sorokina // Issues of modern pediatrics. - 2011. - No. 1. - P. 17-20.
4. Bashmakova N. V., Bashmakova N. V., Kovalev V. V., Litvinova A. M. et al. Survival rate and current perinatal technologies for nursing newborns with extremely low body weight. - 2012. - No. 1. - P. 4-7.
5. Simmons, L.E. Preventing preterm birth and neonatal mortality: exploring the epidemiology, causes, and interventions / L.E.Simmons, C.E.Rubens, G.L. Darmstadt et al. // Semin Perinatol. -2010. - Vol.34, № 6. -Р.408-415.
6. Latini, G. Survival rate and prevalence of bronchopulmonary dysplasia in extremely low birth weight infants / G.Latini, C.De Felice, R. Giannuzzi et al. // Early Hum. Dev. -2013. -Vol. 89, № 1. - Р. 69-73.
7. Vinogradova I. V. The state of health of children with extremely low body weight at birth and in long-term / I.V. Vinogradova, M. V. Krasnov // Bulletin of modern clinical medicine. - 2013. - V. 6. - No. 1. - P. 20-25.
8. Fellman, V. One-year survival of extremely preterm infants after active perinatal care in Sweden / V.Fellman, L.Hellström-Westas, M.Norman // JAMA. -2009. -Vol. 301, № 21. - Р. 2225-2233.
9. Valiulina A. Ya. Problems and prospects of successful nursing and rehabilitation of children born with low and extremely low body weight / A.Ya. Valiulina, E.N. Akhmadeeva, N.N. Kryvkina // Bulletin of modern clinical medicine. - 2013. - No. 6. - P. 34-41.
10. Moore, G.P. Neurodevelopmental outcomes at 4 to 8 years of children born at 22 to 25 weeks’ gestational age. A Meta-analysis / G.P.Moore, B.Lemyre, N.Barrowman et al. // JAMA Pediatrics. -2013. - Vol. 167, № 10. - Р. 967-974.
11. Orcesi, S. Neurodevelopmental outcomes of preterm very low birth weight infants born from 2005 to 2007 / S.Orcesi, I.Olivieri, S.Longo et al. // Eur. J. Paediatr. Neurol. – 2012. - Vol. 16, № 6. - P. 716-723.
12. Bashmakova N. V. Monitoring of children born with extremely low body weight in the perinatal center / N. V. Bashmakova, A. M. Litvinova, G.B. Malgina and others // Obstetrics and gynecology. - 2015. - No. 9. - P. 80-86.
13. Antonov A. G. Intensive therapy and principles of nursing children with extremely low birth weight: methodological letter / A. G. Antonov, O. A. Borisevich, A. S. Burkov et al. - M.: Research Center of Obstetrics, Gynecology and Perinatology, 2011. - 70 p.
14. Management of children born with extremely low body weight (ELBW): a clinical review of international data // Family health: inf. - educ. bullet. - 2011. - No. 2. - P. 2 - 24.
15. Merzlova N.B. Catamnesis of children born with very low and extremely low body weight / N. B. Merzlova, Yu. V. Kurnosova, L. N. Vinokurova et al. // Fundamental research. - 2013. - No. 3. - P. 121-125.
16. Birenbaum, H.J. Reduction in the incidence of chronic lung disease in very low birth weight infant’s results of a quality improvement process in a testiary level neonatal intensive care unit / H.J.Birenbaum // Pediatrics. - 2009. - Vol. 123, № 1. - P. 44-50.
17. Stephanie D. V. Clinical immunology and immunopathology of childhood: a guide for doctors / D. V. Stephanie, Yu. E. Veltischev. – M.: Medicine, 1996. – P. 125-166.
18. Caron, J.E. Multiplex analysis of toll-like receptor-stimulated neonatal cytokine response /J.E.Caron, T.R.La Pine, N.H.Augustine et al.// Neonatology. - 2010. - Vol. 97, № 3. - P. 266-273.
19. Kapitanović Vidak, H. The association between proinflammatory cytokine polymorphisms and cerebral palsy in very preterm infants / H. Kapitanović Vidak, T.Catela Ivković, M.Jokić // Cytokine. -2012. -Vol. 58, №1. - P.57-64.
20. Matsuda, Y. T-cell activation in abnormal perinatal events / Y.Matsuda, H.Kato, K.Imanishi et al.// Microbiol Immunol. - 2010. - Vol. 54, № 1. - P. 38-45.
21. Gromada N. E. Diagnostic value of cytokines in newborns with serious hypoxic injuries of the central nervous system / N.Ye. Gromada // Ural Medical Journal. - 2008. - No. 12. - P. 140-145.
22. Gille, С. Clearance of apoptotic neutrophils is diminished in cord blood monocytes and does not lead to reduced IL-8 production / С.Gille, F.Steffen, K. Lauber et al. // Pediatr. Res. -2009. - Vol. 66, № 5. - Р. 507-512.
23. Charipova B.T. Clinical characteristics of children with extremely low birth weight / B.T. Charipova, G.N. Chistyakova, M. N.Tarasova // Ural Medical Journal. - 2010. - No. 5. - P. 147-151.
24. Luciano, A.A. Alterations in regulatory T cell subpopulations seen in preterm infants /A.A.Luciano, I.M.Arbona-Ramirez, R.Ruiz // PLoS One. - 2014. -Vol.9, № 5. - P.958 - 967.
25. G.S. Koval Features of the immunity of deeply premature newborns in infectious and inflammatory diseases / G.S. Koval, S. A. Samsygin, L. K. Kuznetsova // Russian Bulletin of Perinatology and Pediatrics. – 1999. - No. 2. – P. 8 - 11.
26. Pertseva V.A. Characteristics of humoral immunity of premature newborns, depending on the characteristics of the course of the neonatal period / V. A. Pertseva, N. I. Zakharova // Russian medical journal. - 2011. - No. 31. - P. 11 - 15.
