NHFOV Versus CPAP and NIPPV for Post‐Extubation Support in Severe Meconium Aspiration Syndrome

Objective The present study was conducted to compare the clinical efficacy of three noninvasive respiratory support strategies—nasal continuous positive airway pressure (NCPAP), noninvasive positive pressure ventilation (NIPPV), and noninvasive high‐frequency oscillatory ventilation (NHFOV)—in neonates with severe meconium aspiration syndrome (MAS) following extubation. Methods In this multicenter randomized controlled trial, 170 neonates with severe MAS from three tertiary neonatal intensive care units in Southwest China (Jan 2025–May 2025) were randomized to receive post‐extubation NCPAP ( n = 56), NIPPV ( n = 63), or NHFOV ( n = 51). Primary outcomes were reintubation rate within 7 days and arterial blood gas parameters at 1, 12, and 24 h post‐extubation. Secondary outcomes included ventilation duration, supplemental oxygen days, hospital stay, and complications including but not limited to nasal trauma, abdominal distension, among other predefined complications. The research protocol was prospectively registered in the Chinese Clinical Trial Registry (MR‐50‐24‐057272; registration date: December 28, 2024). Results NHFOV demonstrated significantly lower reintubation rates compared to both NCPAP and NIPPV, while no difference was observed between NIPPV and NCPAP. NHFOV showed superior oxygenation with higher PaO₂ levels and lower PaCO₂ levels across all timepoints. Secondary outcomes favored NHFOV, including shorter durations of invasive ventilation, noninvasive ventilation, and hospital stay, alongside reduced complications (abdominal distension, nasal trauma). No significant differences were observed in BPD, air leaks, severe IVH, or NEC rates among groups. Conclusions NHFOV significantly reduces reintubation rates and improves gas exchange compared to NCPAP and NIPPV in severe MAS neonates, supporting its potential as the preferred post‐extubation respiratory support strategy.