BACKGROUND: Less invasive surfactant administration (LISA) is increasingly used in preterm infants with respiratory distress syndrome (RDS). Understanding its safety profile compared to the INtubation-SURfactant-Extubation (INSURE) or endotracheal tube (ETT) techniques is essential. OBJECTIVE: To evaluate the safety profile of LISA compared to INSURE/ETT in preterm infants with RDS using evidence from randomized and non-randomized studies. METHODS: A systematic literature review identified studies in MEDLINE, EMBASE, and CENTRAL (2010-2024). Arm-level pooled incidence estimates were generated across RCTs and non-randomized studies, and pairwise comparisons of LISA versus INSURE/ETT were conducted in randomized controlled trials (RCTs). Analyses utilized Generalized Linear Mixed Models with random-effects. Subgroups included gestational age (≤ 34 weeks), surfactant type, antenatal steroid exposure (≥ 50%) and sedation and premedication use. RESULTS: Nineteen RCTs (2460 infants) and 26 non-randomized studies (2360 infants) met inclusion criteria. Pairwise comparisons revealed no statistically significant differences between LISA and INSURE/ETT for apnea, bradycardia, cough, hypoxemia, or need for ≥ 2 attempts for successful catheter/ETT placement attempts; however, surfactant regurgitation/reflux occurred more frequently with LISA (OR = 2.29, 95% CI = 1.21-4.33). Adverse event rates were generally higher in non‑randomized studies, with hypoxemia the most frequently reported event across study types (≥ 24%). Subgroup findings were consistent with overall results. CONCLUSION: To our knowledge, this is the first meta-analysis evaluating LISA safety outcomes across both RCTs and non-randomized studies. LISA demonstrates a safety profile broadly comparable to INSURE/ETT for most outcomes. Differences observed in observational studies likely reflect variability in reporting and clinical practice. Standardized training and procedure optimization may further enhance safety.
Sun et al. (Wed,) studied this question.