"In the modern era of Neonatology, an increasingly smaller and more immature population of extremely preterm infants (born ≤ 28 weeks gestational age) is exposed to mechanical ventilation (MV). Given the adverse outcomes associated with MV, every effort is made to extubate as early as possible. However, the scientific basis for determining extubation readiness is imprecise. Currently, the decision to extubate is guided by the physician’s clinical judgment, which is highly subjective and variable. As an adjunct to clinical judgment, studies have turned towards assessments of clinical and physiological parameters during a period of spontaneous breathing. Amongst those assessments, the spontaneous breathing trial (SBT) has increasingly been adopted in neonatal units despite limited evidence to guide its use. In a systematic review and meta-analysis, we found that predictor tests had limited accuracies in the assessment of extubation readiness when compared to clinical judgment alone. In the absence of accurate tools to assess extubation readiness, many infants fail their extubation attempt and require reintubation. Unfortunately, the exact occurrence of reintubation, the patterns by which infants require reintubation and clinical implications of a failed extubation on respiratory outcomes are incompletely understood. Thus, the following thesis aimed to comprehensively decipher the complexities associated with the assessment of extubation readiness and reintubation in extremely preterm infants. We conducted a prospective, multicenter observational study aiming to develop an Automated Predictor of Extubation readiness in extremely preterm infants (APEX, Clinicaltrials.gov-NCT01909947). Infants requiring MV, with birth weights ≤ 1250g and undergoing their first planned extubation were included. Immediately prior to extubation, detailed clinical and cardiorespiratory data was acquired during 60-min on conventional MV and 5-min of spontaneous breathing on endotracheal continuous positive airway pressure (ET-CPAP). Clinical data pertaining to patient demographics, pre-extubation and reintubation characteristics, and final outcomes at discharge was also prospectively collected. A total of 266 infants were recruited. Using the cohort’s clinical database, three sub-analyses were conducted for this thesis. First, we longitudinally described the patterns of reintubation in our cohort. Overall, 47% of infants were reintubated during neonatal hospitalization. Reintubation rates significantly varied as a function of the reason for reintubation and post-extubation observation window used. Reintubations within 7 days post-extubation were primarily related to respiratory causes, while those beyond 14 days were caused by non-respiratory-related reasons. Second, we explored the impact of time interval between extubation and reintubation on the outcome of death or bronchopulmonary dysplasia (BPD), an important respiratory morbidity in this population. Reintubation within any time interval after extubation was associated with significantly increased risk of death/BPD, independent of known confounders. Notably, reintubation within 48h from extubation conferred the greatest odds of death/BPD compared to any other observation window. Lastly, we attempted to understand the safety and value of SBTs in the assessment of extubation readiness during ET-CPAP. We found that 57% of infants developed clinical instability during the 5-min ET-CPAP. After evaluating 41,602 different combinations of clinical events to define SBT pass/fail, all definitions had low accuracies in predicting extubation success compared with clinical judgment alone. All in all, the thesis provides a more structured understanding of the major issues surrounding assessment of extubation readiness and reintubation in extremely preterm infants. It also lays the groundwork for better determining which populations and interventions should be targeted in future work on this complex subject"--