Surfactant administration and risk of bronchopulmonary dysplasia in preterm infants

Preterm birth is a major public health concern with an estimated 11% of all live births affected globally. There is a rapid increase in the incidence of preterm births in many industrialized countries in the past decade. Pulmonary surfactant is a phospholipid/ protein complex mixture reducing surface tension at the air-liquid interface in the alveoli. Defective surfactant metabolism can worsen the prognosis for infants born prematurely. Extremely preterm infants appear to have a greater risk of respiratory distress syndrome, leading to a longer duration of mechanical ventilation, which, in turn, increases the risk of bronchopulmonary dysplasia. Bronchopulmonary dysplasia remains the most common adverse outcome of preterm birth. Early exogenous-surfactant administration plays a pivotal role in the management of preterm infants with respiratory distress syndrome, reducing morbidity and mortality. This literature review summarizes current knowledge on the physiological effects of pulmonary surfactant, its composition, and various routes of administration. This systematic review describes the most common method of surface-active agent administration – INSURE, thin catheter techniques, surfactant aerosolization, and surfactant administration via laryngeal or supraglottic airway (SALSA). The literature search was conducted using the following keywords: preterm birth, lasting effects of premature birth, pulmonary surfactant, exogenous surfactant, preterm infants, bronchopulmonary dysplasia. A detailed systematic analysis of current domestic and international literature on surfactant use was conducted. A total of 64 scientific publications were selected for analysis. Databases of eLibrary, Scopus, PubMed, and MEDLINE were used.

1. Lee HM, Shin J, Kim SY, Kim SY. Factors affecting length of stay according to bronchopulmonary dysplasia severity: a nationwide cohort study in Korea. World J Pediatr. 2024;20(5):470–480. https://doi.org/10.1007/s12519-023-00794-8.

2. Ziganshin AM, Tsitereva EZ, Frolov AL. Premature birth and prematurity in the development of neurological disorders in children. Acta Biomedica Scientifica. 2025;10(3):141–153. (In Russ.) https://doi.org/10.29413/ABS.2025-10.3.15.

3. Deindl P, Diemert A. From structural modalities in perinatal medicine to the frequency of preterm birth. Semin Immunopathol. 2020;42(4):377–383. https://doi.org/10.1007/s00281-020-00805-0.

4. Stensvold HJ, Klingenberg C, Stoen R, Moster D, Braekke K, Guthe HJ et al.; Norwegian Neonatal Network. Neonatal Morbidity and 1-Year Survival of Extremely Preterm Infants. Pediatrics. 2017;139(3):e20161821. https://doi.org/10.1542/peds.2016-1821.

5. Ohuma EO, Moller AB, Bradley E, Chakwera S, Hussain-Alkhateeb L, Lewin A et al. National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis. Lancet. 2023;402(10409):1261–1271. https://doi.org/10.1016/S0140-6736(23)00878-4.

6. Skripnichenko IuP, Baranov II, Tokova ZZ. Statistics of the preterm births. Russian Journal of Human Reproduction. 2014;(4):11–14. (In Russ.) Available at: https://www.mediasphera.ru/issues/problemy-reproduktsii/2014/4/031025-7217201444.

7. Martin JA, Osterman MJK. Shifts in the Distribution of Births by Gestational Age: United States, 2014–2022. Natl Vital Stat Rep. 2024;73(1):1–11. https://doi.org/10.15620/cdc:135610.

8. Александрова ГА, Ахметзянова РР, Голубев НА, Кириллова ГН, Огрызко ЕВ, Оськов ЮИ и др. Здравоохранение в России. М.; 2023. 179 с.

9. Quigley M, Embleton ND, Meader N, McGuire W. Donor human milk for preventing necrotising enterocolitis in very preterm or very low-birthweight infants. Cochrane Database Syst Rev. 2024;9(9):CD002971. https://doi.org/10.1002/14651858.CD002971.pub6.

10. Mudrov VA, Ziganshin AM, Yashchuk AG, Dautova LA, Badranova RS. Possibilities for diagnosis and prediction of preterm labor at the present stage. Kazan Medical Journal. 2021;102(1):47–59. (In Russ.) https://doi.org/10.17816/KMJ2021-47.

11. La Cour EE, Malange VNE, Mohaissen T, Christiansen M, Brok J.S., Gade C, Lausten-Thomsen U, Hedley PL. Causes of neonatal mortality in the European Economic Area and Switzerland: a WHO-based analysis and systematic review. Eur J Pediatr. 2025;184(10):628. https://doi.org/10.1007/s00431-025-06467-0.

12. Zakharova IN, Mal’tsev SV, Zubkov VV, Kur’yaninova VA, Dmitriev AV, Malyavskaya SI et al. Vitamin D, low birthweight preterm and full-term newborns: time for a paradigm shift. Russian Journal of Woman and Child Health. 2020;3(2):142–148. (In Russ.) https://doi.org/10.32364/2618-8430-2020-3-2-142-148.

13. Bozhbanbayeva N, Suleymenova I, Sairankyzy S, Aydarova A, Narmұkhambet M. Survival of preterm infants and their long-term outcomes: A literature review. Reproductive Medicine. 2025;(3):124–136. (In Russ.) https://doi.org/10.37800/RM.3.2025.516.

14. Lin CY, Hsu CH, Chang JH; Taiwan Premature Infant Follow-up Network. Neurodevelopmental outcomes at 2 and 5 years of age in very-low-birth-weight preterm infants born between 2002 and 2009: a prospective cohort study in Taiwan. Pediatr Neonatol. 2020;61(1):36–44. https://doi.org/10.1016/j.pedneo.2019.05.00618.

15. Morniroli D, Tiraferri V, Maiocco G, De Rose DU, Cresi F, Coscia A et al. Beyond survival: the lasting effects of premature birth. Front Pediatr. 2023;11:1213243. https://doi.org/10.3389/fped.2023.121324333.

16. Thébaud B, Goss KN, Laughon M, Whitsett JA, Abman SH, Steinhorn RH et al. Bronchopulmonary dysplasia. Nat Rev Dis Primers. 2019;5(1):78. https://doi.org/10.1038/s41572-019-0127-7.

17. Adams M, Bassler D, Bucher HU, Roth-Kleiner M, Berger TM, Braun J; Swiss Neonatal Network and the Vermont Oxford Network. Variability of Very Low Birth Weight Infant Outcome and Practice in Swiss and US Neonatal Units. Pediatrics. 2018;141(5):e20173436. https://doi.org/10.1542/peds.2017-3436.

18. Miller AN, Shepherd EG, El-Ferzli G, Nelin LD. Multidisciplinary bronchopulmonary dysplasia care. Expert Rev Respir Med. 2023;17(11):989–1002. https://doi.org/10.1080/17476348.2023.2283120.

19. Isayama T, Lee SK, Yang J, Lee D, Daspal S, Dunn M, Shah PS; Canadian Neonatal Network and Canadian Neonatal Follow-Up Network Investigators. Revisiting the Definition of Bronchopulmonary Dysplasia: Effect of Changing Panoply of Respiratory Support for Preterm Neonates. JAMA Pediatr. 2017;171(3):271–279. https://doi.org/10.1001/jamapediatrics.2016.4141.

20. Lee JH, Noh OK, Chang YS; Korean Neonatal Network. Neonatal Outcomes of Very Low Birth Weight Infants in Korean Neonatal Network from 2013 to 2016. J Korean Med Sci. 2019;34(5):e40. https://doi.org/10.3346/jkms.2019.34.e40.

21. Su BH, Hsieh WS, Hsu CH, Chang JH, Lien R, Lin CH; Premature Baby Foundation of Taiwan (PBFT). Neonatal outcomes of extremely preterm infants from taiwan: comparison with Canada, Japan, and the USA. Pediatr Neonatol. 2015;56(1):46–52. https://doi.org/10.1016/j.pedneo.2014.05.002.

22. Kharitonov MA, Rudakov YV, Salukhov VV, Voloshin NI. Role of surfactant in the pathogenesis of bronchopulmonary pathology. Meditsinskiy Sovet. 2023;17(20):52–66. (In Russ.) https://doi.org/10.21518/ms2023-340.

23. Bonadies L, Cavicchiolo ME, Priante E, Moschino L, Baraldi E. Prematurity and BPD: what general pediatricians should know. Eur J Pediatr. 2023;182(4):1505–1516. https://doi.org/10.1007/s00431-022-04797-x.

24. Clements JA. Surface tension of lung extracts. Proc Soc Exp Biol Med. 1957;95(1):170–172. https://doi.org/10.3181/00379727-95-23156.

25. Gruenwald P. Surface tension as a factor in the resistance of neonatal lungs to aeration. Am J Obstet Gynecol. 1947;53(6):996–1007. https://doi.org/10.1016/s0002-9378(16)39775-7.

26. Zizyukina KS, Sarkisyan HA, Vorona LD, Levchenko LA, Shabelnikova EI, Khokhlova AP et al. Surfactant and surfactant therapy in neonates: from the beginning to the modern features of the application. Russian Bulletin of Perinatology and Pediatrics. 2025;70(2/2):5–16. (In Russ.) https://doi.org/10.21508/1027-4065-2025-70-2(p.2)-5-16.

27. Dargaville PA, Herting E, Soll RF. Neonatal surfactant therapy beyond respiratory distress syndrome. Semin Fetal Neonatal Med. 2023;28(6):101501. https://doi.org/10.1016/j.siny.2023.101501.

28. Hasanov SSh, Mirzoeva IA, Aldjanova SB, Gasimova YA, Gulieva GM. Modern representations of the functions of the pulmonary surfactant proteins. Meditsinskie Novosti. 2019;(2):44–46. (In Russ.) Available at: https://www.mednovosti.by/journal.aspx?article=8599.

29. Hallman M, Herting E. Historical perspective on surfactant therapy: Transforming hyaline membrane disease to respiratory distress syndrome. Semin Fetal Neonatal Med. 2023;28(6):101493. https://doi.org/10.1016/j.siny.2023.101493.

30. Lenyushkina AA, Andreyev AV, Ionov OV, Zubkov VV. Review of guidelines on the management of respiratory distress syndrome. Neonatology: News, Opinions, Training. 2024;12(1):84–99. (In Russ.) https://doi.org/10.33029/2308-2402-2024-12-1-84-99.

31. 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. https://doi.org/10.1159/000528914.

32. Ishutsina OV. The surfactant system of the lungs. A review article. Vestnik of Vitebsk State Medical University. 2021;20(4):7–17. (In Russ.) https://doi.org/10.22263/2312-4156.2021.4.7.

33. Smee NJ, O’Shea JE. Can the laryngeal mask airway be used to give surfactant in preterm infants? Arch Dis Child. 2020;105(6):601–603. https://doi.org/10.1136/archdischild-2019-318562.

34. Cummings JJ, Gerday E, Minton S, Katheria A, Albert G, Flores-Torres J et al.; AERO-02 Study Investigators. Aerosolized Calfactant for Newborns With Respiratory Distress: A Randomized Trial. Pediatrics. 2020;146(5):e20193967. https://doi.org/10.1542/peds.2019-3967.

35. Mani S, Rawat M. Less Invasive Surfactant Administration: A Viewpoint. Am J Perinatol. 2024;41(2):211–227. https://doi.org/10.1055/a-2001-9139.

36. Zapata HA, Fort P, Roberts KD, Kaluarachchi DC, Guthrie SO. Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA): A Viable Method for Low-Income and Middle-Income Countries. Front Pediatr. 2022;10:853831. https://doi.org/10.3389/fped.2022.853831.

37. Boskabadi H, Maamouri G, Gharaei Jomeh R, Zakerihamidi M. Comparative study of the effect of the administration of surfactant through a thin endotracheal catheter into trachea during spontaneous breathing with intubation (intubation-surfactant-extubation method). J Clin Neonatol. 2019;8(4):227–231. https://doi.org/10.4103/jcn.JCN_32_19.

38. Sood BG, Cortez J, Kolli M, Sharma A, Delaney-Black V, Chen X. Aerosolized surfactant in neonatal respiratory distress syndrome: Phase I study. Early Hum Dev. 2019;134:19–25. https://doi.org/10.1016/j.earlhumdev.2019.05.005.

39. Minocchieri S, Berry CA, Pillow JJ; CureNeb Study Team. Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2019;104(3):F313–F319. https://doi.org/10.1136/archdischild-2018-315051.

40. Panza R, Laforgia N, Bellos I, Pandita A. Systematic review found that using thin catheters to deliver surfactant to preterm neonates was associated with reduced bronchopulmonary dysplasia and mechanical ventilation. Acta Paediatr. 2020;109(11):2219–2225. https://doi.org/10.1111/apa.15374.

41. Gaertner VD, Thomann J, Bassler D, Rüegger CM. Surfactant Nebulization to Prevent Intubation in Preterm Infants: A Systematic Review and Meta-analysis. Pediatrics. 2021;148(5):e2021052504. https://doi.org/10.1542/peds.2021-052504.

42. Dani C, Talosi G, Piccinno A, Ginocchio VM, Balla G, Lavizzari A et al. A randomized, controlled trial to investigate the efficacy of nebulized poractant alfa in premature babies with respiratory distress syndrome. J Pediatr. 2022;246:40–47.e5. https://doi.org/10.1016/j.jpeds.2022.02.054.

43. Ignatova GL, Antonov VN, Zakharova IA. The use of exogenous surfactant in pulmonological practice. Meditsinskiy Sovet. 2024;(5):41–48. (In Russ.) https://doi.org/10.21518/ms2024-089.

44. Hutcheon JA, Liauw J. Improving the external validity of Antenatal Late Preterm Steroids trial findings. Paediatr Perinat Epidemiol. 2023;37(1):1–8. https://doi.org/10.1111/ppe.12856.

45. Regiroli G, Loi B, Fortas F, Centorrino R, Mosca F, De Luca D. Effect of inspired gas temperature on lung mechan ics and gas exchange in neonates in normothermia or thera peutic hypothermia. Resuscitation. 2021;163:116–123. https://doi.org/10.1016/j.resuscitation.2021.04.015.

46. Hentschel R, Bohlin K, van Kaam A, Fuchs H, Danhaive O. Surfactant replacement therapy: from biological basis to current clinical practice. Pediatr Res. 2020;88(2):176–183. https://doi.org/10.1038/s41390-020-0750-8.

47. Abdel-Latif ME, Davis PG, Wheeler KI, De Paoli AG, Dargaville PA. Surfactant therapy via thin catheter in preterm infants with or at risk of respiratory distress syndrome. Cochrane Database Syst Rev. 2021;5(5):CD011672. https://doi.org/10.1002/14651858.CD011672.pub2.

48. Murphy MC, Galligan M, Molloy B, Hussain R, Doran P. Study protocol for the POPART study – prophylactic oropharyngeal surfactant for preterm infants: a randomised trial. BMJ Open. 2020;10(7):e035994. https://doi.org/10.1136/bmjopen-2019-035994.

49. Wright CJ, Glaser K, Speer CP, Härtel C, Roehr CC. Noninvasive ventilation and exogenous surfactant in times of ever decreasing gestational age: how do we make the most of these tools? J Pediatr. 2022;247:138–146. https://doi.org/10.1016/j.jpeds.2022.04.011.

50. Enzer KG, Baker CD, Wisniewski BL. Bronchopulmonary Dysplasia. Clin Chest Med. 2024;45(3):639–650. https://doi.org/10.1016/j.ccm.2024.03.007.

51. Ramaswamy VV, Abiramalatha T, Bandyopadhyay T, Boyle E, Roehr CC. Surfactant therapy in late preterm and term neonates with respiratory distress syndrome: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2022;107(4):393–397. https://doi.org/10.1136/archdischild2021-322890.

52. Gilfillan M, Bhandari A, Bhandari V. Diagnosis and management of bronchopulmonary dysplasia. BMJ. 2021;375:n1974. https://doi.org/10.1136/bmj.n1974.

53. Fließer E, Jandl K, Lins T, Birnhuber A, Valzano F, Kolb D et al. Lung Fibrosis Is Linked to Increased Endothelial Cell Activation and Dysfunctional Vascular Barrier Integrity. Am J Respir Cell Mol Biol. 2024;71(3):318–331. https://doi.org/10.1165/rcmb.2024-0046OC.

54. Geng Y, Li L, Yan J, Liu K, Yang A, Zhang L et al. PEAR1 regulates expansion of activated fibroblasts and deposition of extracellular matrix in pulmonary fibrosis. Nat Commun. 2022;13(1):7114. https://doi.org/10.1038/s41467-022-35543-4.

55. Blume F, Kirsten H, Ahnert P, Chakraborty T, Gross A, Horn K et al. Verification of immunology-related genetic associations in BPD supports ABCA3 and five other genes. Pediatr Res. 2022;92(1):190–198. https://doi.org/10.1038/s41390-021-01689-y.

56. Vyazovaya IV, Khishtilova PB. Bronchopulmonary dysplasia in children in the focus of phenotype-associated candidate gene polymorphisms. Farmateka. 2021;28(10):46–51. (In Russ.) https://doi.org/10.18565/pharmateca.2021.10.46-51.

57. Huo M, Mei H, Zhang Y, Zhang Y, Liu C. Expression and regulatory mechanism of miR-34a in neonatal rat model of bron-chopulmonary dysplasia induced by hyperoxia. Beijing Da Xue Xue Bao Yi Xue Ban. 2025;57(2):237–244. (In Chinese) https://doi.org/10.19723/j.issn.1671-167X.2025.02.003.

58. Mursalova ZSh. The role of matrix metalloproteinases and markers of apoptosis in the pathogenesis of bronchopulmonary dysplasia in children born with low body weight. International Journal of Applied and Basic Research. 2020;(8):22–26. (In Russ.) Available at: https://applied-research.ru/ru/article/view?id=13110.

59. Zhang X, Zhu L, Wang H, Hu J, Huo J, He S et al. Screening for biomarkers of bronchopulmonary dysplasia: a bioinformatics analysis. Transl Pediatr. 2025;14(4):658–670. https://doi.org/10.21037/tp-2024-595.

60. Shankar N, Thapa S, Shrestha AK, Sarkar P, Gaber MW, Barrios R, Shivanna B. Hyperoxia Disrupts Lung Lymphatic Homeostasis in Neonatal Mice. Antioxidants. 2023;12(3):620. https://doi.org/10.3390/antiox12030620.

61. Hu X, Zheng Y, Fang M, Liang Z, Wen C, Lin J et al. Knockdown of the long noncoding RNA VSIG2-1:1 promotes the angiogenic ability of human pulmonary microvascular endothelial cells by activating the VEGF/PI3K/AKT pathway. Respir Res. 2024;25(1):412. https://doi.org/10.1186/s12931-024-03039-y.

62. El-Saie A, Varghese NP, Webb MK, Villafranco N, Gandhi B, Guaman MC, Shivanna B. Bronchopulmonary dysplasia – associated pulmonary hypertension: An updated review. Semin Perinatol. 2023;47(6):151817. https://doi.org/10.1016/j.semperi.2023.151817.

63. Antonov AG, Ryndin AYu. Surfactant-BL in complex therapy of respiratory disorders in the neonate. Clinical Practice in Pediatrics. 2007;2(4):61–64. (In Russ.) Available at: https://www.phdynasty.ru/katalog/zhurnaly/voprosy-prakticheskoy-pediatrii/2007/tom-2-nomer-4/11391.

64. Guzikov EV, Guzikov OV. Inhalational administration of surfactant to prevent bronchopulmonary dysplasia in premature infants. Meditsinskiy Sovet. 2025;19(11):38–43. (In Russ.) https://doi.org/10.21518/ms2025-264.