Nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure as initial respiratory support during minimally invasive surfactant therapy in preterm infants with respiratory distress syndrome: a retrospective real-world cohort study.

Background: Nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive pressure ventilation (NIPPV) are commonly used as initial non-invasive respiratory support in preterm infants with respiratory distress syndrome (RDS). Minimally invasive surfactant therapy (MIST) is increasingly used to reduce exposure to endotracheal intubation, but data on NIPPV compared to NCPAP during MIST remain limited. This study aimed to compare NIPPV and NCPAP as initial respiratory support during MIST in preterm infants with RDS, with the primary outcome of invasive mechanical ventilation within the first 72 h of life.

Methods: This single-center, retrospective, real-world cohort study included preterm infants (<37 weeks of gestation) with RDS who received MIST within 6 h after birth between January 2021 and January 2025. Infants were grouped according to the initial mode of non-invasive respiratory support: NIPPV (n=170) or NCPAP (n=130). The primary outcome measure was invasive mechanical ventilation (IMV) within the first 72 h of life. Between-group comparisons, multivariable logistic regression adjusted for gestational age and birth weight, inverse probability of treatment weighting, and gestational-age subgroup analyses were performed. Secondary outcome measures included neonatal morbidities, respiratory-support duration, length of hospital stay, surfactant use, and blood gas changes.

Results: Infants in the NIPPV group had lower gestational age (31.37±2.09 vs. 33.51±1.73 weeks, P<0.001) and birth weight (1.60±0.45 vs. 1.99±0.47 kg, P<0.001) than those in the NCPAP group. IMV within 72 h occurred in 46/170 infants (27.1%) in the NIPPV group and 24/130 infants (18.5%) in the NCPAP group [unadjusted risk ratio, 1.47; 95% confidence interval (CI): 0.95-2.27; P=0.08]. After adjustment for gestational age and birth weight, the association was not statistically significant (adjusted odds ratio, 0.605; 95% CI: 0.32-1.14; P=0.12), and the inverse-probability-weighted analysis yielded similar results (P=0.10). No gestational-age subgroup showed a significant difference in the primary outcome. Unadjusted rates of BPD and ROP, as well as non-invasive ventilation duration and length of hospital stay, were higher in the NIPPV group, consistent with greater baseline immaturity. Moderate or severe BPD, ROP requiring surgery, NEC, IVH, hsPDA, sepsis, pneumothorax, and repeat surfactant treatment did not differ significantly between groups. Blood gas profiles improved after surfactant treatment in both groups, with no significant post-treatment between-group differences.

Conclusions: In preterm infants with RDS receiving MIST, initial NIPPV and NCPAP were associated with no statistically significant difference in IMV requirement within 72 h after accounting for major baseline imbalances. NIPPV appears to be a feasible alternative to NCPAP in this setting, but this retrospective study cannot establish non-inferiority or causality. Larger multicenter randomized studies with prespecified stratification are warranted.