Tiny Lungs, Big Decisions: A Meta‐Analysis Comparing Minimally Invasive Surfactant Therapy Versus Intubation–Surfactant–Extubation in Preterm Neonates With Respiratory Distress Syndrome

<b>Background:</b> Neonatal respiratory distress syndrome (NRDS) is a leading cause of morbidity and mortality in preterm infants. Minimally invasive surfactant therapy (MIST) has emerged as a promising alternative to traditional approaches, aiming to reduce mechanical ventilation while maintaining spontaneous breathing. This meta-analysis compares the efficacy and safety of MIST versus the intubation-surfactant-extubation (INSURE) method in preterm neonates with NRDS. <b>Methods:</b> We searched PubMed, Scopus, and Embase for eligible studies. Two independent reviewers screened studies via the Rayyan platform. We included randomized controlled trials and observational cohorts of preterm neonates (< 37 weeks) with NRDS requiring surfactant therapy, comparing MIST and INSURE. Data extraction included study characteristics, demographics, and clinical outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane tools. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was evaluated via <i>I</i> ² statistics. <b>Results:</b> Then, 17 studies (<i>n</i> = 1931 neonates; MIST: 913, INSURE: 932) were included. Baseline characteristics were similar between groups. Mortality did not differ significantly (RR 0.62; 95% CI 0.38-1.01; <i>p</i> = 0.05). MIST was associated with reduced risks of bronchopulmonary dysplasia (RR 0.59; 95% CI 0.45-0.76), intraventricular hemorrhage (RR 0.66; 95% CI 0.48-0.92), patent ductus arteriosus (RR 0.75; 95% CI 0.61-0.93), and pneumothorax (RR 0.54; 95% CI 0.34-0.87). Rates of pulmonary hemorrhage and surfactant reflux were comparable. MIST also resulted in shorter oxygen day requirements (MD -2.45; <i>p</i> = 0.04) and need for mechanical ventilation (RR 0.54; <i>p</i> = 0.002). Duration of ventilation and NICU showed no significant differences. <b>Conclusion:</b> MIST proved to be a safer and more effective alternative to INSURE in preterm infants with NRDS, reducing several complications and mechanical ventilation needs. These findings highlight MIST's potential as a preferred approach, warranting further research to support broader implementation.