Impact of LISA failure on 2-year neurodevelopmental outcomes in preterm infants: a retrospective cohort study

Less invasive surfactant administration (LISA) reduces the need for mechanical ventilation in preterm infants with respiratory distress syndrome. However, some LISA-treated infants require intubation within 72 hours due to continuous positive airway pressure (CPAP) failure (LISA failure, LISA-F). The long-term neurodevelopmental impact of LISA-F remains unclear.

To compare 2-year neurodevelopmental outcome in preterm infants with successful LISA (LISA-S) versus LISA-F and primary intubation for surfactant (PI).

Retrospective cohort study (2015-2023) including infants from 24 to 29 weeks gestational age (GA) with surfactant administration; categorised into three groups: LISA-S (n = 235), LISA-F (n = 117) and PI for surfactant (n = 102). Neurodevelopment was assessed at 2 years corrected age using Bayley Scales of Infant and Toddler Development, Third Edition. Multivariable linear regression adjusted for GA, birth weight and antenatal corticosteroid exposure. A multivariable logistic regression model was constructed to identify independent predictors of cognitive and motor delay.

Adjusted composite motor scores were significantly higher in LISA-S compared with LISA-F infants (adjusted mean difference 6.4; 95% CI 2.0 to 19.0; p = 0.005). No differences were found between LISA-F and PI. Mechanical ventilation within the first 72 hours was the strongest independent predictor of motor delay (aOR (adjusted Odds Ratio) 3.9; 95% CI 1.3 to 11.6; p=0.012).

Preterm infants with LISA-F have significantly worse neurodevelopmental outcomes at 2 years corrected age, comparable to that of PI. Mechanical ventilation, rather than the initial surfactant strategy, emerged as the strongest predictor of developmental impairment, emphasising the importance of preventing CPAP failure after LISA.