Nasal CPAP versus High-Flow Nasal Cannula in Infants with Respiratory Distress Syndrome: A Systematic Review

Background: Respiratory Distress Syndrome (RDS) is a leading cause of respiratory failure in preterm infants, primarily resulting from surfactant deficiency and alveolar collapse. Approximately 15–20% of affected children require respiratory support. Despite advances in antenatal care and non-invasive ventilation that have reduced mortality and complications, the optimal mode of respiratory support remains uncertain. Nasal Continuous Positive Airway Pressure (NCPAP) and High-Flow Nasal Cannula (HFNC) are among the most widely used non-invasive methods for managing RDS—NCPAP enhances lung expansion and oxygenation, while HFNC offers greater comfort and ease of application. Given the ongoing debate over their relative efficacy and safety, this study aimed to systematically review and compare HFNC and NCPAP as initial respiratory support strategies in preterm infants with RDS. Methods: This systematic review was conducted in accordance with PRISMA guidelines. A comprehensive literature search of PubMed, Web of Science, and Scopus was performed to identify studies published between 2015 and 2025 comparing nasal continuous positive airway pressure (nCPAP) with high-flow nasal cannula (HFNC) in preterm or term infants diagnosed with respiratory distress syndrome. Randomized controlled trials and eligible observational studies reporting at least one relevant clinical outcome were considered. Following duplicate removal, titles and abstracts were screened, and potentially relevant articles were assessed for full-text eligibility. Of 565 records identified, 336 were screened, and 12 studies met the inclusion criteria and were included in the final qualitative synthesis. Results: Twelve published studies, conducted between 2017 and 2022, with a total of 1,242 patients, were included. The studies, including preterm infants with respiratory distress, were analyzed. HFNC demonstrated comparable efficacy to NCPAP in terms of respiratory outcomes, including respiratory distress syndrome, bronchopulmonary dysplasia, need for invasive mechanical ventilation, and treatment failure. HFNC was associated with reduced nasal trauma and, in some studies, faster achievement of full enteral feeding. Trends toward shorter non-invasive ventilation duration and hospital stay were observed, but were not consistently statistically significant.  Conclusion: HFNC is a safe and generally effective alternative to NCPAP for preterm infants with respiratory distress, particularly those over 28 weeks’ gestation. HFNC offers advantages in comfort, ease of use, and reduced nasal injury, with similar respiratory outcomes and complication rates compared to NCPAP. Evidence is less clear for extremely low-birth-weight infants, highlighting the need for larger trials to guide optimal use.