A multicenter randomized clinical trial published in JAMA Network Open found that nasal intermittent positive pressure ventilation (PPV) was associated with significantly lower rates of noninvasive ventilation failure than nasal continuous PAP when used as the initial respiratory support strategy in infants with respiratory distress syndrome born extremely preterm.1 The study was conducted by Hui Zhang, MD, from the Department of Pediatrics, Peking University Third Hospital, Beijing, China, and colleagues across neonatal ICUs in China.
Respiratory distress syndrome remains a major cause of morbidity and mortality in infants born before 30 weeks’ gestation. Although minimally invasive surfactant administration (MISA) has gained wider adoption, the optimal form of initial noninvasive respiratory support remains uncertain. Current guidelines generally favor nasal continuous PAP, while evidence supporting nasal intermittent PPV has been limited and inconsistent in extremely preterm populations.1
“In extremely preterm infants treated with MISA, [nasal intermittent PPV] reduced early [noninvasive ventilation] failure compared with [nasal continuous PAP], without any adverse effects,” said Alexander Gipsman, MD, an attending physician with the Division of Pulmonary and Sleep Medicine at Children’s Hospital of Philadelphia. “This study makes a strong case for use of [nasal intermittent PPV] over [nasal continuous PAP] for this specific population of infants with [respiratory distress syndrome] treated with MISA.”
The trial enrolled spontaneously breathing infants born between 24 weeks and 29 weeks, 6 days, of gestation who required noninvasive respiratory support shortly following birth. Participants were randomized to receive either nasal continuous PAP or synchronized nasal intermittent PPV as their primary mode of respiratory support before undergoing MISA. All infants received surfactant through the minimally invasive approach within 120 minutes following birth.
Investigators designed the study as a noninferiority trial and planned to enroll 960 infants. However, investigators halted enrollment after an interim analysis of 312 infants, about one-third of the intended sample size, because prespecified stopping criteria were met. The primary end point was noninvasive ventilation failure within 72 hours, defined as the need for intubation and invasive mechanical ventilation.
Investigators reported that noninvasive ventilation failure within 72 hours occurred in 26.1% of infants assigned to nasal continuous PAP compared with 13.2% of infants assigned to nasal intermittent PPV. The adjusted risk difference was 12.8% (95% CI, 4.2%-21.6%; P = .004), indicating a significant advantage for nasal intermittent PPV. A similar pattern was observed within seven days, with failure rates of 27.5% in the nasal continuous PAP group and 15.1% in the nasal intermittent PPV group.
The study also found differences in resource utilization. Infants initially treated with nasal intermittent PPV required less noninvasive respiratory support and had shorter hospital stays. The nasal intermittent PPV group spent about 18.5 fewer hours on noninvasive ventilation and had a two-day shorter hospitalization on average, Dr. Gipsman said.
Regarding safety outcomes, the authors reported no significant differences between treatment groups in most major neonatal morbidities. Rates of bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH), late-onset sepsis, and mortality were not significantly different. Necrotizing enterocolitis occurred more frequently in the nasal continuous PAP group than in the nasal intermittent PPV group, although the difference did not reach statistical significance.
Despite the positive findings, Dr. Gipsman cautioned against overinterpreting the results.
“The benefit was seen in a short-term, surrogate outcome, and there was no difference between the [nasal intermittent PPV] and [nasal continuous PAP] groups in more clinically meaningful outcomes such as mortality, BPD severity, neurodevelopmental outcomes, or severe IVH,” he said.
He also noted that the trial’s early termination may have influenced the estimated treatment effect.
“The trial’s early termination does not substantially alter the main finding that [nasal intermittent PPV] was superior to [nasal continuous PAP], but it does potentially temper the magnitude of benefit,” Dr. Gipsman said. “Early termination of a trial often overestimates the benefit of the studied intervention.”
References
1. Zhang H, Zhang Y, Zeng L, et al. Nasal continuous positive airway pressure vs nasal intermittent positive pressure ventilation in preterm infants with respiratory distress syndrome: a randomized clinical trial. JAMA Netw Open. 2026;9(6):e2619785. doi:10.1001/jamanetworkopen.2026.19785
