High-Flow Nasal Cannula versus Nasal Continuous Positive Airway Pressure on Postnatal Growth and Feeding in Preterm Infants: A Secondary Analysis of the NIPPN Study

High-flow nasal cannula (HFNC) is generally considered to have fewer enteral feeding problems than nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive-pressure ventilation (NIPPV). However, the effects of HFNC on the feeding outcomes in preterm infants are still controversial. The aim of this study was to assess the effect of HFNC on postnatal growth and feeding.We conducted a secondary analysis of a multicenter randomized controlled trial. Preterm infants born <34 weeks were randomly assigned to the HFNC or NCPAP/NIPPV groups after initial extubation between 2015 and 2018. Data on postnatal growth and oral feeds were analyzed.Among 338 infants in the intention-to-treat analysis, the weight at 36 weeks in the HFNC group was significantly higher than that in the NCPAP/NIPPV group (1,926 vs. 1,804 g, <i>p</i> = 0.04). In the per-protocol analysis, HFNC showed increased daily weight gain from extubation to discharge after adjusting for confounding factors (24.2 vs. 22.4 g/day, adjusted difference 1.65 g/day, 95% confidence interval [CI]: 0.12-3.18). In the subgroup of infants born at 22 to 27 weeks, the weight at 36 weeks was significantly higher in the HFNC group (1,809 vs. 1,730 g, adjusted difference = 113.4 g, 95% CI: 5.0-221.8). There was no significant difference in time at initial and reached full oral feeding.In preterm infants, especially extremely preterm infants, the use of HFNC may be associated with better weight gain. · HFNC showed better weight gain compared with NCPAP/NIPPV in preterm infants.. · HFNC was associated with higher weight at 36 weeks postmenstrual age in extremely preterm infants.. · This study suggests that HFNC may have benefits in postnatal growth among extremely preterm infants..