Efficacy and Safety of a Standardized CPAP Protocol in the Delivery Room in Late Preterm Infants with Infectious and Non-Infectious Lung Diseases

The aim of this study was to evaluate the efficacy and safety of a standardized protocol of delivery room CPAP therapy in late preterm infants with acute neonatal respiratory failure (ARF) caused by various conditions.

Material and methods. A retrospective comparative study of the efficacy of the standardized CPAP protocol in the cohorts of late preterm infants (34–36 weeks) was conducted at the Yekaterinburg Perinatal Center. The comparison group (C, N=256) included infants who received CPAP therapy in the delivery room during 12 months in 2020 before the introduction of the standardized protocol. The study group (S, N=169) included infants treated with standardized CPAP in April-December, 2022. The following subgroups were identified in groups C and S based on the cause of ARF: transient tachypnea of the newborn (TTN; C: N=100; S: N=89), respiratory distress syndrome (RDS; C: N=84; S: N=39), and congenital infection (CI; C: N=54; S: N=37). Other causes of ARF in groups C and S were found in 18 and 4 infants, respectively.

Results. Switching to the standardized CPAP protocol reduced the duration of mechanical ventilation by an average of 24 h (P=0.013), the incidence of documented cerebral ischemia (CI) from 64.1% to 53.2% in all subgroups (P=0.022), the length of stay in the neonatal ward from 12 to 11 days (P=0.001), and the length of stay in the hospital from 16 to 14 days (P=0.001) as well as the incidence of CI in the STTN subgroup vs CTTN (38.2% vs. 61.0%, P=0.002). No significant differences were found in the RDS and CI subgroups. The frequency and duration of binasal CPAP and lung ventilation in the neonatal ICU did not differ between subgroups. Pneumothorax within the first 24 h occurred in one patient in group C and in two patients in group S (P=0.339), all of whom were diagnosed with congenital infection. No damage to the nasal passages was observed in any group. 

Conclusion. The use of a standardized protocol of CPAP therapy for neonates born after 35 weeks of gestation with respiratory failure of any etiology can significantly reduce the severity and duration of illness and should be considered as a basic respiratory strategy in the delivery room when indicated.

1. Hooper S. B., Te Pas A. B., Kitchen M. J. Respiratory transition in the newborn: a three-phase process. Arch Dis Child. Fetal Neonatal Ed. 2016; 101 (3): F266–271. DOI 10.1136/archdischild-2013-305704. PMID: 26542877.

2. Brown M. J., Olver R. E., Ramsden C. A., Strang L. B., Walters D. V. Effects of adrenaline and of spontaneous labour on the secretion and absorption of lung liquid in the fetal lamb. J Physiol. 1983; 344: 137–152. DOI 10.1113/jphysiol.1983.sp014929. PMID: 6655575.

3. Umran R. M. R., Khalil R. M. Association between low cord serum cortisol level and transient tachypnea of the newborn in late preterm and term neonates delivered by elective cesarean section. Am J Perinatol. 2022; 39 (11): 1254–1260. DOI: 10.1055/s-00401722603. PMID: 33454947.

4. Mahoney A. D., Jain L. Respiratory disorders in moderately preterm, late preterm, and early term infants Clin Perinatol. 2013; 40 (4): 665–678. DOI 10.1016/j.clp.2013.07.004. PMID: 24182954.

5. Ovsyannikov D. Yu., Boitsova E. V., Zhestkova M. A., Krsheminskaya I. V., Asherova I. K., Ukraintsev S. E., Mezhinsky S. S. Neonatal pulmonology: Monograph. (ed. Ovsyannikov D. Yu.). M.: Seven-Print; 2022: 168. (in Russ.). ISBN 978-5-91556-757-2. EDN NGFFJV.

6. Shestak E. V., Kovtun O. P., Ksenofontova O. L. Transient tachypnea in newborns: monograph; ed. Kovtun O. P. Doctor of Medical Sciences, Professor, acad. RAS; Ministry of Health of the Russian Federation, Ural State Medical University Yekaterinburg: USMU; 2023: 144. (in Russ.). ISBN 978-5-00168-047-5.

7. Ovsyannikov D. Yu., Volodin N. N. Lung diseases in newborns: diagnostic difficulties, diagnostic criteria and consequences. Pediatrics. G.N Speransky J. = Pediatria. Zhournal im. G. N. Speranskogo. 2022; 101 (3): 170–177. (in Russ.). DOI: 10.24110/0031-403X-2022-101-3-170-177.

8. Antonov A. G., Baibarina E. N., Balashova E. N., Degtyarev D. N., Zubkov V. V., Ivanov D. O., Ionov O. V., et al. Congenital pneumonia: clinical recommendations. Neonatology: News, Opinions, Training = Neonatologiya: Novosti, Mneniya, Obucheniye. 2017; 4: 133–148. (in Russ.). DOI 10.24411/23082402-2017-00049.

9. Shestak E. V. Cystic adenomatous lung malformation of type II in the newborn, problems of early diagnosis. Ural Medical Journal = Uralskiy Meditsinskiy Zhurnal. 2022; 21 (1): 77–84. (in Russ.). DOI: 10.52420/20715943-2022-21-1-77-84.

10. Perepelitsa S. A. Acute respiratory distress syndrome in preterm newborns (morphological study). General Reanimatology = Obshchaya Reanimatologiya. 2020; 16 (1): 35–44. (in Russ.&Eng.). DOI: 10.15360/18139779-2020-1-35-44.

11. Golomidov A. V., Grigoriev E. V., Moses V. G., Moses K. B. Pathogenesis, prognosis and outcomes of multiple organ failure in newborns (review). General Reanimatology = Obshchaya Reanimatologiya. 2022; 18 (6): 37–49. (in Russ.&Eng.). DOI: 10.15360/1813-9779-2022-6-37-49.

12. Osman A. M., El-Farrash R. A., Mohammed E. H. Early rescue Neopuff for infants with transient tachypnea of newborn: a randomized controlled trial. J Matern Fetal Neonatal Med. 2019; 32 (4): 597–603. DOI 10.1080/14767058.2017.1387531. PMID: 28965435.

13. Gizzi C., Klifa R., Pattumelli M. G., Massenzi L., Taveira M., ShankarAguilera S., De Luca D. Continuous positive airway pressure and the burden of care for transient tachypnea of the neonate: retrospective cohort study. Am J Perinatol. 2015; 32 (10): 939–943. DOI: 10.1055/s-0034-1543988. PMID: 25811328.

14. Migliori C., Motta M., Angeli A., Chirico G. Nasal bilevel vs. continuous positive airway pressure in preterm infants. Pediatr Pulmonol. 2005; 40 (5): 426–430. DOI: 10.1002/ppul.20276. PMID: 16155882.

15. Resuscitation and stabilization of newborns in the delivery room: Methodical instructions of the Ministry of Health of the Russian Federation dated March 4, 2020 No. 15-4/I/2-2570 edited by Professor E. N. Baibarina; 2020: 55. (in Russ.). URL: http: //niiomm.ru/attachments/article/370/Реанимация%20и%20стабилизация%20состояния%20новорожденных%20детей%20в%20ро дильном%20зале%202020.pdf.

16. Neonatology: National guidelines: short edition. ed. Volodin N. N. Moscow: GEOTAR–Media; 2019: 896. (in Russ.). ISBN 978–5–9704–4877–9.

17. Shestak E. V., Kovtun O. P., Ksenofontova O. L., Dodrov D. S., Kalyakova N. V. Respiratory strategies affecting the severity of transient tachypnea in newborns. Doctor = Vrach. 2022; (1): 56–60. (in Russ.). DOI: 10.29296/25877305-2022-01-09.

18. Shestak E. V., Kovtun O. P., Ksenofontova O. L., Dodrov D. S. Efficacy and safety of a standardized protocol of CPAP therapy for full-term newborns in delivery room at transient tachypnea: clinical trial with historical control. Issues of Modern Pediatrics = Voprosy Sovremennoy Pediatrii. 2022; 21 (4): 320–330. (in Russ.). DOI: 10.15690/vsp.v21i4.2445.

19. Shestak E. V., Kovtun O. P. Standardized approach to CPAP therapy in the delivery room in full-term infants with congenital infection: observational research. Russian Pediatric Journal/ Rossiyskiy Pediatricheskiy Zhurnal. 2023; 4 (3): 85–93. (in Russ.). DOI: 10.15690/rpj.v4i3.2618.

20. Shestak E. V., Kovtun O. P. Predicting the severity of the course of transient tachypnea in full-term newborns in the delivery room. Russian Pediatric Journal/ Rossiyskiy Pediatricheskiy Zhurnal. 2022; 25 (2): 91–95. (in Russ.). DOI: 10.46563/1560-9561-2022-252-91-95.

21. Mostovoy A. V., Karpova A. L., Volodin N. N., Petrova A. S., Mileva O. I., Zakharova N. I., Dmitriev A. V., et al. Evaluation of the clinical practice of respiratory therapy and outcomes in late preterm (34–36 weeks) with respiratory distress syndrome. Russian Journal of Anesthesiology and Reanimatology/ Anesteziologiya i Reanimatologiya. 2021; (4): 67–72. (in Russ.). DOI: 10.17116/anaesthesiology202104167.

22. Kumar A., Bha B.V Epidemiology of respiratory distress of newborns. Indian J Pediatr. 1996; 63 (1): 93–98. DOI: 10.1007/BF02823875. PMID: 10829971.

23. Ryan C. A. Hughes P. Neonatal respiratory morbidity and mode of delivery at term: influence of timing of elective caesarean section. Br J Obstet Gynaecol. 1995; 102 (10): 843–844. DOI: 10.1111/j.14710528.1995.tb10861.x. PMID: 7547751.

24. Kasap B., Duman N., Ozer E., Tatli M., Kumral A., Ozkan H. Transient tachypnea of the newborn: predictive factor for prolonged tachypnea. Pediatr Intl. 2008; 50 (1): 81–84. DOI: 10.1111/j.1442200X.2007.02535.x. PMID: 18279211.

25. Jain L. Respiratory morbidity in late–preterm infants: prevention is better than cure! Am J Perinatol. 2008; 25 (2): 75–78. DOI: 10.1055/s–2007–1022471. PMID: 18214813.

26. Raju T. N. K., Higgins R.D, Stark A. R., Leveno K. J. Optimizing care and outcome for late–preterm (near–term) infants: a summary of the workshop sponsored by the National Institute of Child Health and Human Development. Pediatrics. 2006; 118 (3): 1207–1214. DOI: 10.1542/peds.2006–0018. PMID: 16951017.

27. Gomez-Lopez N., Galaz J., Miller D., Farias-Jofre M., Liu Z., ArenasHernandez M., Garcia-Flores V., et al. The immunobiology of preterm labor and birth: intra-amniotic inflammation or breakdown of maternal-fetal homeostasis. Reproduction. 2022; 164 (2): R11–R45. DOI: 10.1530/REP-22-0046. PMID: 35559791.

28. Jiang M., Mishu M. M., Lu D., Yin X. A case control study of risk factors and neonatal outcomes of preterm birth. Taiwan J Obstet Gynecol. 2018; 57 (6): 814–818. DOI: 10.1016/j.tjog.2018.10.008. PMID: 30545533.

29. Gibbs R. S. The origins of stillbirth: infectious diseases. Semin Perinatol. 2002; 26 (1): 75–78. DOI: 10.1053/sper.2002.29839. PMID: 11876570.

30. Rawlinson W. D., Hall B., Jones C. A., Jeffery H. E., Arbuckle S. M., Graf N., Howard J., et al. Viruses and other infections in stillbirth: what is the evidence and what should we be doing? Pathology. 2008; 40 (2): 149–160. DOI: 10.1080/00313020701813792. PMID: 18203037.

31. Goldenberg R. L., Thompson C. The infectious origins of stillbirth. Am J Obstet Gynecol. 2003; 189 (3): 861–873. DOI: 10.1067/s00029378(03)00470-8. PMID: 14526331.

32. Puopolo K. M., Benitz W. E., Zaoutis T. E.; Committee on Fetus and Newborn; Committee on Infectious Diseases. Management of neonates born at 35 0/7 weeks‘ gestation with suspected or proven early-onset bacterial sepsis. Pediatrics. 2018; 142 (6): e20182894. DOI: 10.1542/peds.2018-2894. PMID: 30455342.

33. Greco P., Nencini G., Piva I., Scioscia M., Volta C. A., Spadaro S., Neri M., et al. Pathophysiology of hypoxic-ischemic encephalopathy: a review of the past and a view on the future. Acta Neurol Bel. 2020; 120 (2): 277–288. DOI: 10.1007/s13760-020-01308-3. PMID: 32112349.

34. Shestak E. V., Kovtun O. P., Ksenofontova O. L. Assessment of cerebral oxygenation in the development of transient tachypnea in newborns. Pediatrics. G. N. Speransky J. = Pediatria. Zhournal im. G. N. Speranskogo. 2023; 102 (1): 27–35. (in Russ.). DOI: 10.24110/0031-403X-2023-102-1-27-35.

35. Shestak E. V., Kovtun O. P., Bazarny V. V., Polushina L. G., Maksimova A.Yu. Assessment of the level of neurotrophic factors VEGF, BDNF, β-NGF in newborns with transient tachypnea and cerebral ischemia in comparison with healthy children. Pediatrics. G.N Speransky J. = Pediatria. Zhournal im. G. N. Speranskogo. 2024; 103 (1): 49–57. (in Russ.). DOI: 10.24110/0031-403X2024-103-1-49-57.