# Non-Invasive Surfactant Administration in Preterm Infants

**Authors:** Faten Budajaja, Nadine Lahage, Ivan L. Hand

PMC · DOI: 10.3390/children13010150 · 2026-01-21

## TL;DR

This review examines non-invasive methods for delivering surfactant to preterm infants, aiming to reduce complications and improve outcomes compared to traditional intubation.

## Contribution

The paper provides a comprehensive evaluation of non-invasive surfactant delivery techniques and their clinical outcomes in preterm infants.

## Key findings

- Non-invasive surfactant techniques reduce mechanical ventilation and BPD rates compared to traditional methods.
- LISA/MIST shows the most consistent evidence for improved outcomes, while other methods face technical and design limitations.
- Long-term neurodevelopmental data for all techniques remain limited.

## Abstract

Background: Although surfactant replacement therapy has been a cornerstone of respiratory distress syndrome (RDS) management for decades, traditional delivery via endotracheal intubation and mechanical ventilation is associated with procedure-related complications and increased risk of bronchopulmonary dysplasia (BPD). These concerns have driven the development of less invasive surfactant administration strategies. Objective: This review aims to summarize and evaluate the current literature on less invasive surfactant delivery techniques used in preterm infants with RDS, with a focus on their feasibility, efficacy, and short- and long-term neonatal outcomes. Methods: We reviewed the available literature evaluating less invasive surfactant administration methods, including InSurE, Less Invasive Surfactant Therapy/Minimally Invasive Surfactant Therapy (LISA/MIST), surfactant administration via laryngeal mask airway (SALSA/LMA), pharyngeal administration, and nebulized surfactant. We compared major outcomes, namely the need for mechanical ventilation, incidence of BPD, procedural complications and long-term neurodevelopmental outcomes. Results: Non-invasive surfactant administration techniques have been associated with reduced exposure to mechanical ventilation and lower rates of BPD compared with conventional approaches. Studies on LISA/MIST demonstrate the most consistent evidence in reducing the need for mechanical ventilation and BPD, while other techniques such as LMA-assisted delivery and nebulization show promise but remain limited by device constraints, gestational age applicability, and heterogeneous study designs. Long-term neurodevelopmental outcome data remain sparse across all techniques. Conclusions: Non-invasive surfactant administration represents an important advancement in the management of RDS. While several techniques offer potential advantages over traditional intubation-based delivery, further high-quality studies are required to optimize patient selection, standardize techniques, develop safe and effective delivery devices, and evaluate long-term neurodevelopmental outcomes.

## Linked entities

- **Diseases:** respiratory distress syndrome (MONDO:0009971), bronchopulmonary dysplasia (MONDO:0019091)

## Full-text entities

- **Diseases:** RDS (MESH:D012128), BPD (MESH:D001997)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC12840295