Neonatal-Perinatal Medicine Fellow, PGY-6 Yale School of Medicine New haven, Connecticut, United States
Background: In 1959, Avery and Mead identified surfactant deficiency as the key factor in neonatal respiratory distress syndrome (RDS), laying the foundation for exogenous surfactant therapy. In 1971, Gregory introduced continuous positive airway pressure (CPAP), offering a gentler alternative to invasive ventilation. Fujiwara’s landmark 1980 trial demonstrated the clinical efficacy of animal-derived surfactant, catalyzing randomized trials and FDA approval in the 1990s. Objective: To trace the historical evolution of surfactant therapy and neonatal airway strategies, from early intubation and prophylactic surfactant to CPAP-first care, INSURE (INtubation-SURfactant-Extubation), and Less Invasive Surfactant Administration (LISA) or Surfactant Administration through Laryngeal or Supraglottic Airways (SALSA) and to highlight pivotal trials and guidelines that reshaped practice. Design/Methods: Narrative historical review of key discoveries, clinical trials, meta-analyses, and resuscitation guidelines influencing surfactant delivery and airway management. Results: Early trials confirmed the efficacy of exogenous surfactant and highlighted advantages of animal-derived over synthetic preparations. Meta-analyses supported higher initial dosing of poractant alfa for improved outcomes. Large randomized controlled trials such as COIN and SUPPORT shifted practice toward CPAP-first with selective surfactant, reducing mechanical ventilation exposure. The INSURE technique minimized ventilation time, while LISA enabled surfactant delivery via thin catheters in spontaneously breathing infants. Recent advances include the OPTIMIST-A trial (2021) evaluating LISA, aerosolized surfactant RCTs (2020) reducing intubation needs, and the ongoing Neo-INSPIRe trial assessing nebulized surfactant (2023). Updated guidelines reinforce CPAP-first and selective surfactant, while recent reviews report LISA superiority (2024). SALSA guidelines (2025) standardized LMA surfactant delivery, expanding non-invasive options.
Conclusion(s): Over six decades, neonatal respiratory care has progressed from routine intubation and prophylactic surfactant administration to CPAP-first strategies incorporating less invasive techniques such as LISA and SALSA. Current research priorities focus on refining these approaches and advancing novel methods, including aerosolized surfactant delivery, while developing standardized protocols to ensure safety and efficacy across diverse clinical settings
