UNLABELLED: To evaluate the accuracy of the lung ultrasound score (LUS) in predicting ventilatory weaning failure during neonatal hospitalization in the NICU and to identify factors associated with weaning failure, including corrected gestational age (CGA). This prospective, longitudinal, pragmatic and observational cohort study included neonates on mechanical ventilation for at least 48 h. The primary outcome was the accuracy of lung ultrasound in predicting 3-day weaning failure, with the ROC curve used to determine the best LUS cutoff (sensitivity and specificity). Among 55 neonates, the pre-extubation LUS did not show statistical significance in predicting weaning failure (AUC 0.61
95% CI: 0.46-0.76, p = 0,169). In the subgroup analysis, a score ≥ 4 suggests the need for ventilatory support after extubation (area under the curve [AUC] = 0.91, 95% CI: 0.80-1.0, p <
0.001) in neonates with GA ≥ 28 weeks. In extremely preterm infants, the pre-extubation LUS was not statistically significant in predicting weaning failure (AUC = 0.38, 95% CI: 0-0.77, p = 0.535). In contrast, CGA ≥ 28.7 weeks at extubation was predictor of successful weaning within 3 days (AUC = 0.95, 95% CI: 0.85-1.0, p <
0.001). CONCLUSION: LUS show promise in predicting weaning failure, though its accuracy may be limited in extremely preterm infants, highlighting the need for further well-powered studies. CGA at extubation also emerges as a key consideration in this population, warranting confirmation through robust future research. WHAT IS KNOWN: • Identifying the optimal timing for extubation is crucial, as both prolonged mechanical ventilation and failed extubation are linked to increased morbidity. • Lung ultrasound plays a well-established role in diagnosing various neonatal lung pathologies, allowing clinicians to make rapid, bedside decisions for the treatment of newborns. WHAT IS NEW: • LUS appears to be accurate in predicting weaning failure, though its accuracy may be lower in extremely preterm infants. • In extremely preterm infants, CGA may play an important role in extubation decision-making. • These findings are hypothesis-generating and warrant further investigation in future studies.