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Abstract
Respiratory disorders remain a leading cause of early neonatal mortality among preterm infants, despite advances in life-saving respiratory technologies.
The aim of the study – was to identify differences in the clinical course of the neonatal period, as well as in the expression of surfactant proteins and apoptosis factors, in preterm infants who died during the early neonatal period.
Materials and methods. A retrospective study was conducted, analyzing medical records from 35 cases of early neonatal mortality among preterm infants (aged 0-168 hours) born at a gestational age of 28-33 weeks between 2017 and 2024. The infants were divided into two groups: Group 1 consisted of newborns who did not receive surfactant replacement therapy (n = 11), and Group 2 consisted of newborns who received such therapy (n = 24). Statistical hypotheses were tested using Student’s t-test and Fisher’s exact test.
Results. The aggregate clinical and morphological data indicate the existence of two distinct phenotypes of lung tissue injury in newborns. The first – «surfactant deficiency with Bcl-2 overexpression» – predominates in the group that did not receive exogenous surfactant; this morphological profile correlates significantly with extremely low survival rates. The second – «prematurity with therapeutic response» – is characteristic of the group treated with exogenous surfactant and is associated with reduced Bcl-2 expression, elevated SP-C levels, and, consequently, increased survival. A key result of the study is also the extremely strong inverse correlation between Bcl-2 and SP-C (r = -0.94).
Conclusion. The integration of histological and immunohistochemical data using machine learning methods demonstrated that the efficacy of surfactant therapy is determined not only by gestational age but also by the baseline molecular-morphological profile of the lung tissue. A combination of low SP-C levels and BCL-2 overexpression serves as a reliable adverse prognostic marker, reflecting profound impairment of alveolar epithelial function and resistance to standard therapy.
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References
1. Sweet DG, Carnielli VP, Greisen G, Hallman M, Klebermass-Schrehof K, Ozek E, et al. European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update. Neonatology. 2023; 120(1): 3-23. doi: 10.1159/000528914
2. Yaremenko AV, Pechnikova NA, Porpodis K, Damdoumis S, Aggeli A, Theodora P, Domvri K. Association of Fetal Lung Development Disorders with Adult Diseases: A Comprehensive Review. J Pers Med. 2024; 14(4): 368. doi: 10.3390/JPM14040368
3. Nogee LM, Ryan RM. Genetic Testing for Neonatal Respiratory Disease. Children (Basel). 2021; 8(3): 216. doi: 10.3390/CHILDREN8030216
4. Pukhtinskaya MG, Estrin VV. Algorithm for predicting death in newborns with respiratory pathology and perinatal damage to the central nervous system on artificial ventilation. Messenger of Anesthesiology and Resuscitation. 2024; 21(1): 65-74. Russian (Пухтинская М.Г., Эстрин В.В. Алгоритм прогнозирования летального исхода у новорожденных с респираторной патологией и перинатальным поражением центральной нервной системы, находящихся на искусственной вентиляции легких //Вестник анестезиологии и реаниматологии. 2024. Т. 21, № 1. С. 65-74.) doi: 10.24884/2078-5658-2024-21-1-65-74
5. Chen IL, Chen HL. New developments in neonatal respiratory management. Pediatr Neonatol. 2022; 63(4): 341-347. doi: 10.1016/j.pedneo.2022.02.002
6. Perepelitsa SA. Acute Respiratory Distress Syndrome in Preterm Newborns (Morphological Study). General Reanimatology. 2020; 16(1): 35-44. Russian (Перепелица С.А. Острый респираторный дистресс-синдром у недоношенных новорожденных (морфологическое исследование) //Общая реаниматология. 2020. Т. 16, № 1. С. 35-44.) doi: 10.15360/1813-9779-2020-1-35-44
7. Golomidov AV, Grigoriev EV, Moses VG, Moses KB. Pathogenesis, prognosis and outcomes of multiple organ failure in newborns (review). General Reanimatology. 2022; 6: 37-49. Russian (Голомидов А.В., Григорьев Е.В., Мозес В.Г., Мозес К.Б. Патогенез, прогнозирование и исходы синдрома полиорганной недостаточности у новорожденных (обзор) //Общая реаниматология. 2022. № 6. С. 37-49.) doi: 10.15360/1813-9779-2022-6-37-49
8. Khalilova SU. Pathomorphology of Respiratory Organs: Distress Syndrome in Newborns. CARJIS. 2025; 4(6): 182-187. Russian (Халилова С.У. Патоморфология респираторных органов: дистресс-синдром у новорожденных //CARJIS. 2025. Т. 4, № 6. С. 182-187.)
9. Palabiyik AA. The role of Bcl 2 in controlling the transition between autophagy and apoptosis. Mol Med Rep. 2025; 32(1): 172. doi: 10.3892/mmr.2025.13537
10. Ladokhin AS. Regulation of Apoptosis by the Bcl-2 Family of Proteins: Field on a Brink. Cells. 2020; 9(9): 2121. doi:10.3390/cells9092121
11. Pathare-Ingawale P, Gogate N, Thube Y, Mansour SMA, Chavan-Gautam P, Wagh G, Joshi S. Association between proNGF receptors and apoptotic factors in human placentae. Placenta. 2023; 139: 43-48. doi: 10.1016/j.placenta.2023.05.011
12. Pathare-Ingawale P, Chavan-Gautam P. The balance between cell survival and death in the placenta: Do neurotrophins have a role? Syst Biol Reprod Med. 2022; 68(1): 3-12. doi:10.1080/19396368.2021.1980132
13. Shahzad T, Chao CM, Hadzic S, Behnke J, Biebach L, Böttcher-Friebertshäuser E, et al. TRAIL protects the immature lung from hyperoxic injury. Cell Death Dis. 2022; 13(7): 614. doi: 10.1038/s41419-022-05072-5
14. van Kaam AH, Niemarkt HJ, Onland W. Timing of surfactant treatment in respiratory distress syndrome. Semin Fetal Neonatal Med. 2023; 28(6): 101495. doi: 10.1016/j.siny.2023.101495
15. Stavinskaya OA, Dobrodeeva LK, Patrakeeva VP. Associations between blood concentrations of cytotoxic CD8+ cells and lymphocyte apoptosis in healthy humans. Human ecology. 2021; 9: 4-10. Russian (Ставинская О.А., Добродеева Л. К., Патракеева В. П. Уровни апоптотической гибели лимфоцитов в зависимости от содержания цитотоксических клеток cd8+ у практически здоровых людей //Экология человека. 2021. № 9. С. 4-10.) doi: 10.33396/1728-0869-2021-9-4-10
16. Kalinin RE, Suchkov IA, Klimentova EA, Egorov AA, Povarov VO. Apoptosis in vascular pathology: present and future. I.P. Pavlov Russian Medical Biological Herald. 2020; 28(1): 79-87. Russian (Калинин Р.Е., Сучков И.А., Климентова Э.А., Егоров А.А., Поваров В.О. Апоптоз в сосудистой патологии: настоящее и будущее //Российский медико-биологический вестник им. акад. И.П. Павлова. 2020. Т. 28, № 1. С. 79-87.) doi: 10.23888/PAVLOVJ202028179-87
17. Inviyaeva EV, Nikitina IV, Krechetova LV, Krog-Jensen OA, Vtorushina VV, Lenyushkina AA, et al. Plasma cytokine profiles in preterm neonates with congenital pneumonia in the first week of life. Obstetrics and gynecology, 2021; 8: 133-142. Russian (Инвияева Е.В., Никитина И.В., Кречетова Л.В., Крог-Йенсен О.А., Вторушина В.В., Ленюшкина А.А., и др. Профиль цитокинов в плазме периферической крови недоношенных детей с врожденной пневмонией на первой неделе жизни //Акушерство и Гинекология. 2021. № 8. С. 143-152.) doi: 10.18565/aig.2021.8.143-152