Comparative efficacy and safety of noninvasive respiratory support in very preterm infants (<32 weeks' gestation): a network meta-analysis

Background The optimal noninvasive respiratory support strategy for very preterm infants among NCPAP, NIPPV, NHFOV, HFNC, and NIV-NAVA remains unclear. Methods This network meta-analysis of nine randomized controlled trials involving 1,449 preterm infants compared the efficacy and safety of these five modes evaluated in eight trials of early respiratory support and one trial of support after clinical stabilization. Results The primary efficacy outcomes were treatment failure or endotracheal intubation, bronchopulmonary dysplasia (BPD), and mortality; safety outcomes included retinopathy of prematurity, patent ductus arteriosus, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and air leak syndrome. NIPPV (RR = 0.47, 95% CI 0.34 to 0.65) and NHFOV (RR = 0.62, 95% CI 0.43 to 0.91) were associated with lower risks of treatment failure or intubation than NCPAP, and NIPPV showed a lower risk than HFNC (RR = 0.53, 95% CI 0.29 to 0.98). The latter difference was not maintained after exclusion of the trial evaluating support after stabilization. No significant differences were observed in BPD or mortality. NIPPV was associated with a lower risk of NEC than NCPAP (RR = 0.60, 95% CI 0.37 to 0.97), although differences in severity thresholds make this finding exploratory. No significant differences were found for the other safety outcomes, including IVH. Conclusions These findings suggest potential respiratory benefits without establishing equivalent efficacy or safety. Interpretation is limited by differences in outcome definitions and clinical settings; assessable comparisons were provisionally rated as low or very low certainty. Applicability specifically to infants born before 32 weeks remains uncertain. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261403266 , PROSPERO CRD (420261403266).