Intratracheal budesonide mixed with surfactant to prevent bronchopulmonary dysplasia in extremely preterm infants: a critical review of recent evidence
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Published:
Jul 15, 2026
Keywords:
Bronchopulmonary dysplasia; infant, extremely premature; budesonide; pulmonary surfactants; glucocorticoids; neonatology.
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Abstract
Introduction: Bronchopulmonary Dysplasia (BPD) is the leading cause of chronic respiratory morbidity in extremely preterm infants. The intratracheal administration of budesonide, mixed with surfactant, aims to directly reduce pulmonary inflammation. Objective: synthesize recent knowledge regarding the intratracheal budesonide-surfactant therapeutic strategy for the prevention of BPD in extremely preterm infants. Methodology: narrative review of medical literature published from 2021 to 2026. Results: small studies and several meta-analyses suggest preliminary evidence of benefit, but contemporary multicenter trials in extremely preterm infants do not consistently confirm a reduction in BPD, death, or composite respiratory outcomes. Conclusion: the combination of budesonide and surfactant for the prevention of BPD is pathophysiologically rational, but its widespread use is not justified, except in the research setting, until high-quality evidence becomes available. General field of study: medicine. Specific field of study: neonatology. Type of study: Narrative literature review.
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Leyva Proenza, C. A., Goyes Guerra, M. B., Cordones Garcés, A. G., & Andrade Riera, S. M. (2026). Intratracheal budesonide mixed with surfactant to prevent bronchopulmonary dysplasia in extremely preterm infants: a critical review of recent evidence. Anatomía Digital, 9(3), 28-39. https://doi.org/10.33262/anatomiadigital.v9i3.3714
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References
1. Jeon GW, Oh M, Chang YS. Increased bronchopulmonary dysplasia along with decreased mortality in extremely preterm infants. Scientific Reports [Internet]. 2025 [cited 2026Apr.07];15(1):8720-. Available from: https://www.nature.com/articles/s41598-025-93466-8
2. Tang W, Chen S, Shi D, Ai T, Zhang L, Huang Y, et al. Effectiveness and safety of early combined utilization of budesonide and surfactant by airway for bronchopulmonary dysplasia prevention in premature infants with RDS: A meta‐analysis. Pediatric Pulmonology [Internet]. 2022 [cited 2026Apr.07];57(2):455-469. Available from: https://pubmed.ncbi.nlm.nih.gov/34783192/
3. Gharehbaghi M, Ganji S, Mahallei M. A Randomized clinical trial of intratracheal administration of surfactant and budesonide combination in comparison to surfactant for prevention of bronchopulmonary dysplasia. Oman Medical Journal [Internet]. 2021 [cited 2026Apr.07];36(4):e289-e289. Available from: https://www.omjournal.org/articleDetails.aspx?coType=1&aId=2957
4. Marzban A, Mokhtari S, Tavakkolian P, Mansouri R, Jafari N, Maleki A. The impact of combined administration of surfactants and intratracheal budesonide compared to surfactants alone on bronchopulmonary dysplasia (BPD) and mortality rate in preterm infants with respiratory distress syndrome: a single-blind randomized clinical trial. BMC Pediatrics [Internet]. 2024 [cited 2026Apr.07];24(1):262. Available from: https://link.springer.com/article/10.1186/s12887-024-04736-9
5. Manley BJ, Kamlin COF, Donath SM, Francis KL, Cheong JLY, Dargaville PA, et al. Intratracheal budesonide mixed with surfactant for extremely preterm infants: the PLUSS randomized clinical trial. JAMA [Internet]. 2024 [cited 2026Apr.07];332(22):1889. 1899. Available from: https://jamanetwork.com/journals/jama/fullarticle/2826118
6. Ambalavanan N, Carlo WA, Nowak KJ, Wiener LE, Cosby SS, Bhatt AJ, et al. Early intratracheal budesonide to reduce bronchopulmonary dysplasia in extremely preterm infants: the Budesonide in Babies (BiB) randomized clinical trial. JAMA [Internet]. 2025 [cited 2026Apr.07];334(16):1452-1462. Available from: https://jamanetwork.com/journals/jama/fullarticle/2839355
7. Alves Gomes AD, Bulhões E, Costa do Amaral D, Matos de Sousa LF, Lima Júnior EC, Alves Ferreira JA, et al. Efficacy of intratracheal budesonide plus surfactant vs. Surfactant alone on bronchopulmonary dysplasia in preterm Infants: A meta-analysis of randomized controlled trials. Paediatric Respiratory Reviews [Internet]. 2025 [cited 2026Apr.07];56:68-74. Available from: https://doi.org/10.1016/j.prrv.2025.02.003
8. Zhang M, Zhang W, Liao H. Efficacy and safety of different inhaled corticosteroids for bronchopulmonary dysplasia prevention in preterm infants: A systematic review and meta-analysis. Respiratory Medicine and Research [Internet]. 2024 [cited 2026Apr.07];85. Available from: https://pubmed.ncbi.nlm.nih.gov/38744231/
9. Phattraprayoon N, Tan B, Na Takuathung M. Efficacy of pulmonary surfactant with budesonide in premature infants: a systematic review and meta-analysis. PLoS One [Internet]. 2025 [cited 2026Apr.07];20(1):e0312561. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0312561
10. Liu MM, Ji L, Dong MY, Zhu XF, Wang HJ. Efficacy and safety of intratracheal administration of budesonide combined with pulmonary surfactant in preventing bronchopulmonary dysplasia: a prospective randomized controlled trial. Zhongguo Dang Dai Er Ke Za Zhi [Internet]. 2022 [cited 2026Apr.07];24(1):78-84. Available from: https://pubmed.ncbi.nlm.nih.gov/35177180/
11. Zhang Y, Liu M, Li Y, Chi D, Zhang J, Zhang Y. Efficacy of lung surfactant combined with budesonide in improving bronchopulmonary dysplasia and growth of very low birth weight infants. Frontiers in Pediatrics [Internet]. 2025 [cited 2026Apr.07];13: 1686811. Available from: https://pubmed.ncbi.nlm.nih.gov/41383573/
12. Ahmad AS, Fliman PJ, Peebles PJ, Gorski DP, Menda NS, Eickhoff JC, et al. Effectiveness of intratracheal surfactant mixed with budesonide for prevention of bronchopulmonary dysplasia. Pediatric Pulmonology [Internet]. 2025 [cited 2026Apr.07];60(5). Available from: https://pubmed.ncbi.nlm.nih.gov/40415480/
13. Vemireddy K, Panigrahy N, Jamalpuri V, Venkatlakshmi A, Chirla DK. Comparison of intratracheal administration of surfactant with or without budesonide to prevent bronchopulmonary dysplasia: a parallel randomized pilot study. Research Square [Internet]. 2025 [cited 2026Apr.07];39(6):479-85. Available from: https://doi.org/10.21203/rs.3.rs-1339070/v1
14. Kuitunen I, Res G, Räsänen K, Vassallo A, Autilio C, Gualano MR, et al. Surfactant-budesonide combination to prevent death or bronchopulmonary dysplasia: a systematic review and meta-analysis. Neonatology [Internet]. 2026 [cited 2026Apr.07];1-19. Available from: https://karger.com/article/doi/10.1159/000552203
15. Abiramalatha T, Ramaswamy VV, Bandyopadhyay T, Somanath SH, Shaik NB, Pullattayil AK, et al. Interventions to prevent bronchopulmonary dysplasia in preterm neonates. JAMA Pediatrics [Internet]. 2022 [cited 2026Apr.07];176(5):502-516. Available from: https://jamanetwork.com/journals/jamapediatrics/fullarticle/2789460
16. Ekraminasab S, Noorishadkam M, Neamatzadeh H, Lookzadeh MH, Mirjalili SR, Mazaheri M, et al. Meta-analysis of budesonide and surfactant combination for the prevention of bronchopulmonary dysplasia in preterm neonates based on gestational age. Frontiers in Pediatrics [Internet]. 2025 [cited 2026Apr.07];13: 1518957. Available from: https://www.frontiersin.org/articles/10.3389/fped.2025.1518957/full
17. Thébaud B, Goss KN, Laughon M, Whitsett JA, Abman SH, Steinhorn RH, et al. Bronchopulmonary dysplasia. Nature Reviews Disease Primers [Internet]. 2019 [cited 2026Apr.07]; 5(1):78. Available from: http://dx.doi.org/10.1038/s41572-019-0127-7
18. Yeh TF, Lin HC, Chang CH, Wu TS, Su BH, Li TC, et al. Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study. Pediatrics [Internet]. 2008 [cited 2026Apr.07];121(5):e1310-e1318. Available from: https://pubmed.ncbi.nlm.nih.gov/18426851/
19. Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, et al. Intratracheal administration of budesonide/surfactant to prevent bronchopulmonary dysplasia. American Journal of Respiratory and Critical Care Medicine [Internet]. 2016 [cited 2026Apr.07];193(1):86-95. Available from: https://academic.oup.com/ajrccm/article/193/1/86/8508850
20. Bancalari E, Jain D, Jobe AH. Prevention of bronchopulmonary dysplasia: are intratracheal steroids with surfactant a magic bullet? American Journal of Respiratory and Critical Care Medicine [Internet]. 2016 [cited 2026Apr.07];193(1):12-13. Available from: https://pubmed.ncbi.nlm.nih.gov/26720788/
21. Dani C. Intratracheal budesonide/surfactant for preventing bronchopulmonary dysplasia. American Journal of Respiratory and Critical Care Medicine [Internet]. 2016 [cited 2026Apr.07];194(1):123. Available from: https://pubmed.ncbi.nlm.nih.gov/27367894/
22. García Veloz ML, Leyva Proenza CA, Goyes Guerra MB, Falconi Valencia MC. Treatment of patent ductus arteriosus in neonatology: status and future challenges. Anatomía Digital [Internet]. 2024 [cited 2026Apr.07]; 7(3.1): 89-103. Available from: https://doi.org/10.33262/anatomiadigital.v7i3.1.3145
23. Jara Santamaría JC, Torres Morán LE, Trujillo Jácome C, Yánez Moretta P, Cumbicus Naranjo GF, Mantilla Naranjo SG. (2020). Germinal matrix hemorrhage: can be detected effectively. Anatomía Digital [Internet]. 2020 [cited 2026Apr.07]; 3(3): 26-43. Available from: https://doi.org/10.33262/anatomiadigital.v3i3.1328
2. Tang W, Chen S, Shi D, Ai T, Zhang L, Huang Y, et al. Effectiveness and safety of early combined utilization of budesonide and surfactant by airway for bronchopulmonary dysplasia prevention in premature infants with RDS: A meta‐analysis. Pediatric Pulmonology [Internet]. 2022 [cited 2026Apr.07];57(2):455-469. Available from: https://pubmed.ncbi.nlm.nih.gov/34783192/
3. Gharehbaghi M, Ganji S, Mahallei M. A Randomized clinical trial of intratracheal administration of surfactant and budesonide combination in comparison to surfactant for prevention of bronchopulmonary dysplasia. Oman Medical Journal [Internet]. 2021 [cited 2026Apr.07];36(4):e289-e289. Available from: https://www.omjournal.org/articleDetails.aspx?coType=1&aId=2957
4. Marzban A, Mokhtari S, Tavakkolian P, Mansouri R, Jafari N, Maleki A. The impact of combined administration of surfactants and intratracheal budesonide compared to surfactants alone on bronchopulmonary dysplasia (BPD) and mortality rate in preterm infants with respiratory distress syndrome: a single-blind randomized clinical trial. BMC Pediatrics [Internet]. 2024 [cited 2026Apr.07];24(1):262. Available from: https://link.springer.com/article/10.1186/s12887-024-04736-9
5. Manley BJ, Kamlin COF, Donath SM, Francis KL, Cheong JLY, Dargaville PA, et al. Intratracheal budesonide mixed with surfactant for extremely preterm infants: the PLUSS randomized clinical trial. JAMA [Internet]. 2024 [cited 2026Apr.07];332(22):1889. 1899. Available from: https://jamanetwork.com/journals/jama/fullarticle/2826118
6. Ambalavanan N, Carlo WA, Nowak KJ, Wiener LE, Cosby SS, Bhatt AJ, et al. Early intratracheal budesonide to reduce bronchopulmonary dysplasia in extremely preterm infants: the Budesonide in Babies (BiB) randomized clinical trial. JAMA [Internet]. 2025 [cited 2026Apr.07];334(16):1452-1462. Available from: https://jamanetwork.com/journals/jama/fullarticle/2839355
7. Alves Gomes AD, Bulhões E, Costa do Amaral D, Matos de Sousa LF, Lima Júnior EC, Alves Ferreira JA, et al. Efficacy of intratracheal budesonide plus surfactant vs. Surfactant alone on bronchopulmonary dysplasia in preterm Infants: A meta-analysis of randomized controlled trials. Paediatric Respiratory Reviews [Internet]. 2025 [cited 2026Apr.07];56:68-74. Available from: https://doi.org/10.1016/j.prrv.2025.02.003
8. Zhang M, Zhang W, Liao H. Efficacy and safety of different inhaled corticosteroids for bronchopulmonary dysplasia prevention in preterm infants: A systematic review and meta-analysis. Respiratory Medicine and Research [Internet]. 2024 [cited 2026Apr.07];85. Available from: https://pubmed.ncbi.nlm.nih.gov/38744231/
9. Phattraprayoon N, Tan B, Na Takuathung M. Efficacy of pulmonary surfactant with budesonide in premature infants: a systematic review and meta-analysis. PLoS One [Internet]. 2025 [cited 2026Apr.07];20(1):e0312561. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0312561
10. Liu MM, Ji L, Dong MY, Zhu XF, Wang HJ. Efficacy and safety of intratracheal administration of budesonide combined with pulmonary surfactant in preventing bronchopulmonary dysplasia: a prospective randomized controlled trial. Zhongguo Dang Dai Er Ke Za Zhi [Internet]. 2022 [cited 2026Apr.07];24(1):78-84. Available from: https://pubmed.ncbi.nlm.nih.gov/35177180/
11. Zhang Y, Liu M, Li Y, Chi D, Zhang J, Zhang Y. Efficacy of lung surfactant combined with budesonide in improving bronchopulmonary dysplasia and growth of very low birth weight infants. Frontiers in Pediatrics [Internet]. 2025 [cited 2026Apr.07];13: 1686811. Available from: https://pubmed.ncbi.nlm.nih.gov/41383573/
12. Ahmad AS, Fliman PJ, Peebles PJ, Gorski DP, Menda NS, Eickhoff JC, et al. Effectiveness of intratracheal surfactant mixed with budesonide for prevention of bronchopulmonary dysplasia. Pediatric Pulmonology [Internet]. 2025 [cited 2026Apr.07];60(5). Available from: https://pubmed.ncbi.nlm.nih.gov/40415480/
13. Vemireddy K, Panigrahy N, Jamalpuri V, Venkatlakshmi A, Chirla DK. Comparison of intratracheal administration of surfactant with or without budesonide to prevent bronchopulmonary dysplasia: a parallel randomized pilot study. Research Square [Internet]. 2025 [cited 2026Apr.07];39(6):479-85. Available from: https://doi.org/10.21203/rs.3.rs-1339070/v1
14. Kuitunen I, Res G, Räsänen K, Vassallo A, Autilio C, Gualano MR, et al. Surfactant-budesonide combination to prevent death or bronchopulmonary dysplasia: a systematic review and meta-analysis. Neonatology [Internet]. 2026 [cited 2026Apr.07];1-19. Available from: https://karger.com/article/doi/10.1159/000552203
15. Abiramalatha T, Ramaswamy VV, Bandyopadhyay T, Somanath SH, Shaik NB, Pullattayil AK, et al. Interventions to prevent bronchopulmonary dysplasia in preterm neonates. JAMA Pediatrics [Internet]. 2022 [cited 2026Apr.07];176(5):502-516. Available from: https://jamanetwork.com/journals/jamapediatrics/fullarticle/2789460
16. Ekraminasab S, Noorishadkam M, Neamatzadeh H, Lookzadeh MH, Mirjalili SR, Mazaheri M, et al. Meta-analysis of budesonide and surfactant combination for the prevention of bronchopulmonary dysplasia in preterm neonates based on gestational age. Frontiers in Pediatrics [Internet]. 2025 [cited 2026Apr.07];13: 1518957. Available from: https://www.frontiersin.org/articles/10.3389/fped.2025.1518957/full
17. Thébaud B, Goss KN, Laughon M, Whitsett JA, Abman SH, Steinhorn RH, et al. Bronchopulmonary dysplasia. Nature Reviews Disease Primers [Internet]. 2019 [cited 2026Apr.07]; 5(1):78. Available from: http://dx.doi.org/10.1038/s41572-019-0127-7
18. Yeh TF, Lin HC, Chang CH, Wu TS, Su BH, Li TC, et al. Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study. Pediatrics [Internet]. 2008 [cited 2026Apr.07];121(5):e1310-e1318. Available from: https://pubmed.ncbi.nlm.nih.gov/18426851/
19. Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, et al. Intratracheal administration of budesonide/surfactant to prevent bronchopulmonary dysplasia. American Journal of Respiratory and Critical Care Medicine [Internet]. 2016 [cited 2026Apr.07];193(1):86-95. Available from: https://academic.oup.com/ajrccm/article/193/1/86/8508850
20. Bancalari E, Jain D, Jobe AH. Prevention of bronchopulmonary dysplasia: are intratracheal steroids with surfactant a magic bullet? American Journal of Respiratory and Critical Care Medicine [Internet]. 2016 [cited 2026Apr.07];193(1):12-13. Available from: https://pubmed.ncbi.nlm.nih.gov/26720788/
21. Dani C. Intratracheal budesonide/surfactant for preventing bronchopulmonary dysplasia. American Journal of Respiratory and Critical Care Medicine [Internet]. 2016 [cited 2026Apr.07];194(1):123. Available from: https://pubmed.ncbi.nlm.nih.gov/27367894/
22. García Veloz ML, Leyva Proenza CA, Goyes Guerra MB, Falconi Valencia MC. Treatment of patent ductus arteriosus in neonatology: status and future challenges. Anatomía Digital [Internet]. 2024 [cited 2026Apr.07]; 7(3.1): 89-103. Available from: https://doi.org/10.33262/anatomiadigital.v7i3.1.3145
23. Jara Santamaría JC, Torres Morán LE, Trujillo Jácome C, Yánez Moretta P, Cumbicus Naranjo GF, Mantilla Naranjo SG. (2020). Germinal matrix hemorrhage: can be detected effectively. Anatomía Digital [Internet]. 2020 [cited 2026Apr.07]; 3(3): 26-43. Available from: https://doi.org/10.33262/anatomiadigital.v3i3.1328