Factors Associated with Intubation After Less Invasive Surfactant Administration (LISA); A Single-Center Cohort from Saudi Arabia

Background: Less invasive surfactant administration (LISA) can reduce exposure to mechanical ventilation in preterm infants, but factors associated with LISA failure in routine practice remain uncertain, particularly outside Europe. Methods: We performed a single-center retrospective cohort at King Abdulaziz Medical City, Riyadh (June 2023–June 2025). Inborn preterm infants at 26–34 weeks of gestation who received LISA as first-line surfactant therapy were included. The primary outcome was LISA failure, defined as intubation within 72 h for apnea, escalating oxygen requirement, or respiratory acidosis. Secondary outcomes included intraventricular hemorrhage (IVH), NICU length of stay, and other major morbidities. Multivariable logistic regression (gestational age as the anchor variable with a limited number of additional covariates) was used to identify predictors of failure and of IVH. Kaplan–Meier methods (log-rank test) were used to compare time to NICU discharge. Results: Forty-one infants were included (median gestational age: 30 weeks; median birth weight: 1300 g). LISA failure occurred in 39% of the cohort. Compared with infants with successful LISA, those who failed were more premature (median GA: 28 vs. 29 weeks; p = 0.009), had lower birth weight (1100 g vs. 1270 g; p = 0.011), higher IVH rates (38% vs. 8%; p = 0.020), and longer NICU stay (60 vs. 40 days; p = 0.041). Lower gestational age was the only independent factors associated with LISA failure (adjusted OR 1.44; 95% CI: 1.07–1.95; p = 0.018). LISA failure was independently associated with IVH (adjusted OR 10.08; 95% CI: 1.29–78.50; p = 0.027). Kaplan–Meier analysis showed significantly prolonged NICU stay among infants with LISA failure (p = 0.011). Conclusions: LISA is feasible in a high-acuity Middle Eastern NICU. However, failure—closely linked to lower gestational age—is associated with IVH and prolonged hospitalization. Careful patient selection and procedural planning are essential to optimize outcomes.