LISA failure and school-age motor impairment in very preterm infants: a retrospective cohort study

Background Less invasive surfactant administration (LISA) reduces the need for early invasive mechanical ventilation in preterm infants with respiratory distress syndrome. However, LISA failure (LISA-F), defined as the need for mechanical ventilation within 72 hours of life, occurs in a substantial proportion of cases. While the short-term complications of LISA-F are well described, the impact on long-term neurodevelopment remains unclear. Methods This retrospective cohort study included preterm infants born between 24+0 and 29+6 weeks' gestation who received surfactant therapy in a tertiary neonatal intensive care unit. Infants were classified into three groups: LISA success (LISA-S), LISA-F, or primary intubation (PI). Neurodevelopmental outcomes were assessed at 5.5 years of age using WPPSI-IV-NL for cognition and mABC-2 for motor function. Multivariate analyses were adjusted for gestational age, birth weight z-score, antenatal corticosteroid exposure and severe intraventricular hemorrhage. Results Among 295 infants, 225 (76.3%) received LISA; 32% experienced LISA-F. Follow-up data were available for 168 of 246 survivors (68.3%). LISA-F was independently associated with lower motor scores than LISA-S (adjusted β -2.1; p=0.004), but not with cognitive outcomes. Infants who underwent primary intubation had significantly lower cognitive scores than those in the LISA-S group (adjusted β -5.1; p=0.038). Invasive mechanical ventilation within the first 72 hours was independently associated with motor developmental delay (aOR:3.9; 95% CI 1.2-13.2; p=0.028) Conclusion LISA-F is associated with adverse motor outcomes at school age. Our findings suggest that the early respiratory trajectory after LISA is more relevant to long term motor development than the initial surfactant administration technique itself.