<![CDATA[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.]]>
