Background:Mechanical ventilation (MV) stands as a crucial life-saving therapeutic intervention. Optimizing the time of weaning from MV to reduce its duration and avoid failure of the process represents a major challenge. Patients on mechanical ventilation frequently encounter respiratory muscle dysfunction, complicating the weaning process. Oxidative stress plays a pivotal role in mechanical ventilation-induced respiratory muscle dysfunction. Serum malondialdehyde (MDA) arises from the oxidative breakdown of polyunsaturated fatty acids and is frequently utilized as a biomarker of oxidative stress. Objective:The main aim of this study was to assess the efficacy of serum malondialdehyde as a contributory factor in predicting failure of weaning from mechanical ventilation in neonates. Methods:This prospective cohort study was conducted on 31 neonates recruited from the neonatal intensive care unit at Ain Shams University Hospitals between March 2023 and November 2023. All the participating neonates were mechanical ventilation-dependent for more than 72 hours. All of them were candidates for weaning according to standard weaning protocol and have successfully passed the spontaneous breathing trial (SBT). Serum MDA levels were assessed for all participants by Enzyme-linked immunosorbent assay (ELISA) pre-SBT, at 30 minutes, and 72 hours post-SBT. Based on the definition of weaning failure, which involves the need for re-intubation within 72 hours after a successful SBT, the enrolled neonates were further categorized into two groups: those with weaning success and those with weaning failure. Results:The weaning success group included 14 neonates, whereas the weaning failure group included 17 neonates.Serum malondialdehyde levels were significantly higher pre-SBT, at 30 minutes post-SBT, and 72 hours post-SBT in the weaning failure group compared to the weaning success group. A value exceeding 223 ng/ml was identified as a cut-off for serum MDA to predict failure of neonatal weaning from MV with a sensitivity of 94% and specificity of 100%. Conclusion:Evaluating serum MDA levels could serve as a valuable biomarker in predicting failure of neonatal weaning from mechanical ventilation. Keywords:Weaning, Mechanical Ventilation, MDA.