BACKGROUND: Heated humidified high-flow nasal cannula (HHHFNC) is gaining popularity as a mode of respiratory support. We updated a systematic review and meta-analyses examining the efficacy and safety of HHHFNC compared with standard treatments for preterm infants. The primary outcome was the need for reintubation for preterm infants following mechanical ventilation (post-extubation analysis) or need for intubation for preterm infants not previously intubated (analysis of primary respiratory support). METHODS: We searched PubMed, Medline, Embase, and the Cochrane Library for randomized controlled trials (RCTs) of HHHFNC versus standard treatments. Meta-analysis was conducted using Review Manager 5.3. RESULTS: The post-extubation analysis included ten RCTs (n = 1,201), and the analysis of primary respiratory support included ten RCTs (n = 1,676). There were no statistically significant differences for outcomes measuring efficacy, including the primary outcome. There were statistically significant differences favoring HHHFNC versus nasal cannula positive airway pressure (NCPAP) for air leak (post-extubation, risk ratio (RR) 0.29, 95 percent confidence interval (CI) 0.11 to 0.76, I2 = 0%) and nasal trauma (post-extubation 0.35, 95 percent CI 0.27 to 0.46, I2 = 5%; primary respiratory support RR 0.52, 95 percent CI 0.37 to 0.74; I2 = 27%). Studies, particularly those of primary respiratory support, included very few preterm infants with gestational age (GA) < 28 weeks. CONCLUSIONS: HHHFNC may offer an efficacious and safe alternative to NCPAP for some infants but evidence is lacking for preterm infants with GA <= 28 weeks.

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