skip to main content

COMPARISON OF HIGH-FLOW NASAL CANNULA AND NASAL CONTINUOUS POSITIVE AIRWAY PRESSURE FOR RESPIRATORY SUPPORT IN PRETERM INFANTS: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

*Fadhilah Apriliandri  -  Faculty of Medicine, Universitas Pembangunan Nasional Veteran Jakarta, Indonesia, Indonesia
Danny Yovita Maharani  -  Faculty of Medicine, Universitas Lampung, Indonesia, Indonesia
Amelina Ratih Listyaningrum  -  Faculty of Medicine, Universitas Yarsi, Indonesia, Indonesia
Open Access Copyright 2026 Fadhilah Apriliandri
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Citation Format:
Abstract

Background: High-flow nasal cannula (HFNC) has gained increasing use as a non-invasive respiratory support for preterm infants, yet its relative effectiveness and safety compared with continuous positive airway pressure (CPAP) remain uncertain. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) enrolling preterm infants (<37 weeks gestation) who received either HFNC or CPAP. Comprehensive searches were conducted in PubMed, Cochrane Library, ClinicalTrials.gov, Scopus, and EBSCOhost from 29 May, 2025 to August 17, 2025. The principal outcomes were treatment failure and the requirement for mechanical ventilation. Results: Twenty-one RCTs including 2,289 participants met eligibility criteria. Pooled analyses demonstrated no significant differences between HFNC and CPAP in preventing treatment failure (RR 1.18; 95% CI 0.91–1.52) or the need for mechanical ventilation (RR 0.97; 95% CI 0.81–1.16). HFNC was associated with lower rates of nasal trauma, abdominal distension, and pneumothorax. Other endpoints, such as duration of oxygen therapy, time to achieve full enteral feeds, and length of hospitalization, did not differ substantially between the two groups. Conclusion: HFNC appears to be as effective as CPAP in preterm infants, with additional advantages in safety and patient comfort. It may therefore represent a reasonable alternative to CPAP, provided that clinical context and individual patient factors are taken into account.

Keywords: high-flow nasal cannula; continuous positive airway pressure; preterm infants; meta-analysis

Article Metrics:

Article Info
  1. DiBlasi RM. Neonatal Noninvasive Ventilation Techniques: Do We Really Need to Intubate? Respir Care [Internet]. 2011 Sep 1;56(9):1273–97. Available from: https://www.liebertpub.com/doi/10.4187/respcare.01376
  2. Motojima Y, Ito M, Oka S, Uchiyama A, Tamura M, Namba F. Use of high‐flow nasal cannula in neonates: Nationwide survey in Japan. Pediatr Int [Internet]. 2016 Apr 20;58(4):308–10. Available from: https://onlinelibrary.wiley.com/doi/10.1111/ped.12903
  3. Alallah J. Early CPAP versus surfactant in extremely preterm infants. J Clin Neonatol [Internet]. 2012;1(1):12. Available from: https://journals.lww.com/10.4103/2249-4847.92233
  4. Manley BJ. Nasal High-Flow Therapy for Preterm Infants. Clin Perinatol [Internet]. 2016 Dec;43(4):673–91. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0095510816300641
  5. Dunn MS, Kaempf J, de Klerk A, de Klerk R, Reilly M, Howard D, et al. Randomized Trial Comparing 3 Approaches to the Initial Respiratory Management of Preterm Neonates. Pediatrics [Internet]. 2011 Nov 1;128(5):e1069–76. Available from: https://publications.aap.org/pediatrics/article/128/5/e1069/30950/Randomized-Trial-Comparing-3-Approaches-to-the
  6. Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG LA. Early CPAP versus Surfactant in Extremely Preterm Infants. N Engl J Med [Internet]. 2010 May 27;362(21):1970–9. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa0911783
  7. Schmolzer GM, Kumar M, Pichler G, Aziz K, O’Reilly M, Cheung PY. Non-invasive versus invasive respiratory support in preterm infants at birth: systematic review and meta-analysis. BMJ [Internet]. 2013 Oct 17;347(oct17 3):f5980–f5980. Available from: https://www.bmj.com/lookup/doi/10.1136/bmj.f5980
  8. Armfield M, West G. Use of Vapotherm for respiratory support with neonates. Paediatr Care. 2009;21(1):27–30
  9. Lissauer T, Duke T, Mellor K, Molyneux L. Nasal CPAP for neonatal respiratory support in low and middle-income countries. Arch Dis Child - Fetal Neonatal Ed [Internet]. 2017 May;102(3):F194–6. Available from: https://fn.bmj.com/lookup/doi/10.1136/archdischild-2016-311653
  10. Jatana KR, Oplatek A, Stein M, Phillips G, Kang DR, Elmaraghy CA. Effects of Nasal Continuous Positive Airway Pressure and Cannula Use in the Neonatal Intensive Care Unit Setting. Arch Otolaryngol Neck Surg [Internet]. 2010 Mar 15;136(3):287. Available from: http://archotol.jamanetwork.com/article.aspx?doi=10.1001/archoto.2010.15
  11. Lavizzari A, Colnaghi M, Ciuffini F, Veneroni C, Musumeci S, Cortinovis I, et al. Heated, Humidified High-Flow Nasal Cannula vs Nasal Continuous Positive Airway Pressure for Respiratory Distress Syndrome of Prematurity. JAMA Pediatr [Internet]. 2016 Aug 8; Available from: http://archpedi.jamanetwork.com/article.aspx?doi=10.1001/jamapediatrics.2016.1243
  12. Fleeman N, Mahon J, Bates V, Dickson R, Dundar Y, Dwan K, et al. The clinical effectiveness and cost-effectiveness of heated humidified high-flow nasal cannula compared with usual care for preterm infants: systematic review and economic evaluation. Health Technol Assess (Rockv) [Internet]. 2016 Apr;20(30):1–68. Available from: https://www.journalslibrary.nihr.ac.uk/hta/hta20300/
  13. Wilkinson D, Andersen C, O’Donnell CP, De Paoli AG, Manley BJ. High flow nasal cannula for respiratory support in preterm infants. Cochrane Database Syst Rev [Internet]. 2016 Feb 22;2016(2). Available from: http://doi.wiley.com/10.1002/14651858.CD006405.pub3
  14. Kang WQ, Xu BL, Liu DP, Zhang YD, Guo J, Li ZH, et al. Efficacy of heated humidified high-flow nasal cannula in preterm infants aged less than 32 weeks after ventilator weaning. Chinese J Contemp Pediatr. 2016;18(6):488–91
  15. Zheng G, Huang X qiu, Zhao H hui, Jin GX, Wang B. The Effect of the Treatment with Heated Humidified High-Flow Nasal Cannula on Neonatal Respiratory Distress Syndrome in China: A Single-Center Experience. Can Respir J [Internet]. 2017;2017:1–6. Available from: https://www.hindawi.com/journals/crj/2017/3782401/
  16. Schmid F, Olbertz DM, Ballmann M. The use of high-flow nasal cannula (HFNC) as respiratory support in neonatal and pediatric intensive care units in Germany – A nationwide survey. Respir Med [Internet]. 2017 Oct;131:210–4. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0954611117303049
  17. Hong H, Li X xia, Li J, Zhang Z qun. High-flow nasal cannula versus nasal continuous positive airway pressure for respiratory support in preterm infants: a meta-analysis of randomized controlled trials. J Matern Neonatal Med [Internet]. 2021 Jan 17;34(2):259–66. Available from: https://www.tandfonline.com/doi/full/10.1080/14767058.2019.1606193
  18. Luo K, Huang Y, Xiong T, Tang J. High-flow nasal cannula versus continuous positive airway pressure in primary respiratory support for preterm infants: A systematic review and meta-analysis. Front Pediatr [Internet]. 2022 Nov 21;10. Available from: https://www.frontiersin.org/articles/10.3389/fped.2022.980024/full
  19. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions [Internet]. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions. Wiley; 2019. 1–694 p. Available from: https://onlinelibrary.wiley.com/doi/book/10.1002/9781119536604
  20. Armanian AM, Iranpour R, Parvaneh M, Salehimehr N, Feizi A, Hajirezaei M. Heated Humidified High Flow Nasal Cannula (HHHFNC) is not an effective method for initial treatment of Respiratory Distress Syndrome (RDS) versus nasal intermittent mandatory ventilation (NIMV) and nasal continuous positive airway pressure (NCPAP). J Res Med Sci [Internet]. 2019 Jan;24(1). Available from: https://journals.lww.com/01222967-201924000-00073
  21. Chen, Jia & Gao, Wei-Wei & Xu, Fang & DU, Lan-Lan & Zhang, Tao & Ling, Xing & Li WT. Comparison of clinical efficacy of heated humidified high flow nasal cannula versus nasal continuous positive airway pressure in treatment of respiratory distress syndrome in very low birth weight infants. Zhongguo Dang Dai Er Ke Za Zhi. 2015;
  22. Ciuffini F, Colnaghi M, Lavizzari A, Mercadante D, Musumeci S, Mosca F. High Flow Nasal Cannulae in preterm infants. La Pediatr Medica e Chir. 2013;35(3)
  23. Cresi F, Maggiora E, Lista G, Dani C, Borgione SM, Spada E, et al. Effect of Nasal Continuous Positive Airway Pressure vs Heated Humidified High-Flow Nasal Cannula on Feeding Intolerance in Preterm Infants With Respiratory Distress Syndrome. JAMA Netw Open [Internet]. 2023 Jul 12;6(7):e2323052. Available from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2807159
  24. Demirel G, Vatansever B, Tastekin A. High Flow Nasal Cannula versus Nasal Continuous Positive Airway Pressure for Primary Respiratory Support in Preterm Infants: A Prospective Randomized Study. Am J Perinatol [Internet]. 2021 Feb 28;38(03):237–41. Available from: http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1696673
  25. Farhat AS, Mohammadzadeh A, Mamuri GA, Saeidi R, Noorizadeh S. Comparison of nasal non-invasive ventilation methods in preterm neonates with respiratory distress syndrome. Iran J Neonatol. 2018;9(4):53–60
  26. Grover R, Singh P, Shubham S, Priyadarshi M, Chaurasia S, Basu S. Delivery Room Respiratory Stabilization of Preterm Neonates: A Randomized, Controlled Trial. Indian J Pediatr. 2022;89(8):793–800
  27. Kadir MA, Mollah AH, Basak R, Choudhury AM, Ahmed S. High flow nasal cannulae versus nasal continuous positive airway pressure in neonates with respiratory distress syndrome managed with INSURE method: A randomized clinical trial. Iran J Med Sci [Internet]. 2016;41(6):208–14. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5106564/
  28. Mostafa-Gharehbaghi M, Mojabi H. Comparing the Effectiveness of Nasal Continuous Positive Airway Pressure (NCPAP) and High Flow Nasal Cannula (HFNC) in Prevention of Post Extubation Assisted Ventilation. Zahedan J Res Med Sci [Internet]. 2015 Jun 27;17(6). Available from: https://brieflands.com/articles/zjrms-984
  29. Murki S, Singh J, Khant C, Kumar Dash S, Oleti TP, Joy P, et al. High-Flow Nasal Cannula versus Nasal Continuous Positive Airway Pressure for Primary Respiratory Support in Preterm Infants with Respiratory Distress: A Randomized Controlled Trial. Neonatology [Internet]. 2018;113(3):235–41. Available from: https://karger.com/article/doi/10.1159/000484400
  30. Öktem A, Yiğit Ş, Çelik HT, Yurdakök M. Comparison of four different non-invasive respiratory support techniques as primary respiratory support in preterm infants. Turk J Pediatr. 2021;63(1):23–30
  31. Roberts CT, Owen LS, Manley BJ, Frøisland DH, Donath SM, Dalziel KM, et al. Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants. N Engl J Med [Internet]. 2016 Sep 22;375(12):1142–51. Available from: http://www.nejm.org/doi/10.1056/NEJMoa1603694
  32. Shin J, Park K, Lee EH, Choi BM. Humidified High Flow Nasal Cannula versus Nasal Continuous Positive Airway Pressure as an Initial Respiratory Support in Preterm Infants with Respiratory Distress: a Randomized, Controlled Non-Inferiority Trial. J Korean Med Sci [Internet]. 2017;32(4):650. Available from: https://jkms.org/DOIx.php?id=10.3346/jkms.2017.32.4.650
  33. Shirvani TE, Nayeri FS, Shariat M, Nafs NN, Mirjalili MR, Hosseini SN, et al. Continuous positive airway pressure or humidified high flow nasal cannula for respiratory distress syndrome: A randomized control trial among premature neonates. Iran J Neonatol. 2020;11(4):50–6
  34. Shokouhi M, Basiri B, Sabzehei MK, Mahdiankhoo M, Pirdehghan A. Efficacy and Complications of Humidified High-Flow Nasal Cannula Versus Nasal Continuous Positive Airway Pressure in Neonates with Respiratory Distress Syndrome After Surfactant Therapy. Iran Red Crescent Med J [Internet]. 2019 Feb 19;In Press(In Press). Available from: https://archive.ircmj.com/article/21/2/ircmj-21-2-83615.pdf
  35. Singh S, Ananthan A, Nanavati R. Post-INSURE Administration of Heated Humidified High-Flow Therapy Versus Nasal Continuous Positive Airway Pressure in Preterm Infants More Than 28 Weeks Gestation with Respiratory Distress Syndrome: A Randomized Non-Inferiority Trial. J Trop Pediatr [Internet]. 2022 Jun 6;68(4). Available from: https://academic.oup.com/tropej/article/doi/10.1093/tropej/fmac062/6649677
  36. Uchiyama A, Okazaki K, Kondo M, Oka S, Motojima Y, Namba F, et al. Randomized Controlled Trial of High-Flow Nasal Cannula in Preterm Infants After Extubation. Pediatrics [Internet]. 2020 Dec 1;146(6). Available from: https://publications.aap.org/pediatrics/article/146/6/e20201101/33523/Randomized-Controlled-Trial-of-High-Flow-Nasal
  37. Yengkhom R, Suryawanshi P, Gupta B, Deshpande S. Heated Humidified High-Flow Nasal Cannula vs. Nasal Continuous Positive Airway Pressure for Post-extubation Respiratory Support in Preterm Infants: A Randomized Controlled Trial. J Trop Pediatr [Internet]. 2021 Jan 29;67(1). Available from: https://academic.oup.com/tropej/article/doi/10.1093/tropej/fmaa082/5974086
  38. Yoder BA, Stoddard RA, Li M, King J, Dirnberger DR, Abbasi S. Heated, Humidified High-Flow Nasal Cannula Versus Nasal CPAP for Respiratory Support in Neonates. Pediatrics [Internet]. 2013 May 1;131(5):e1482–90. Available from: https://publications.aap.org/pediatrics/article/131/5/e1482/31320/Heated-Humidified-High-Flow-Nasal-Cannula-Versus
  39. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol [Internet]. 2014 Dec 19;14(1):135. Available from: https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/1471-2288-14-135
  40. Bruet S, Butin M, Dutheil F. Systematic review of high-flow nasal cannula versus continuous positive airway pressure for primary support in preterm infants. Arch Dis Child - Fetal Neonatal Ed [Internet]. 2022 Jan;107(1):56–9. Available from: https://fn.bmj.com/lookup/doi/10.1136/archdischild-2020-321094
  41. Conte F, Orfeo L, Gizzi C, Massenzi L, Fasola S. Rapid systematic review shows that using a high‐flow nasal cannula is inferior to nasal continuous positive airway pressure as first‐line support in preterm neonates. Acta Paediatr [Internet]. 2018 Oct;107(10):1684–96. Available from: https://onlinelibrary.wiley.com/doi/10.1111/apa.14396
  42. Jeon GW. Respiratory support with heated humidified high flow nasal cannula in preterm infants. Korean J Pediatr [Internet]. 2016;59(10):389. Available from: http://www.e-cep.org/journal/view.php?doi=10.3345/kjp.2016.59.10.389

Last update:

No citation recorded.

Last update:

No citation recorded.