Selection Criteria for the systematic review
This systematic review included studies that compared the effectiveness of the two respiratory strategies (permissive hypercapnia versus targeting normocapnia) on mortality and morbidity in preterm infants on mechanical ventilation. All published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were eligible for inclusion in this review. Unpublished RCTs were eligible if sufficient information on risk of bias assessment was obtained. No language restrictions were applied, but the selected articles were required to have an English abstract. This systematic review excluded studies without sufficient data regarding the outcomes to be summarized, duplicate studies or data, and animal studies. Studies were excluded if they assessed only infants on noninvasive mechanical ventilation without intubation (e.g., those on continuous positive airway pressure [CPAP] or high-flow nasal cannula). Six important outcomes were selected a priori for assessment in this systematic review: (1) mortality at discharge from the neonatal intensive care unit (NICU) or at postmenstrual age of 36 weeks; (2) bronchopulmonary dysplasia (BPD), defined as oxygen use or respiratory pressure support [e.g., CPAP, high-flow nasal cannula at a rate of >2 L/min] at postmenstrual age of 36 weeks; (3) a composite outcome of death or BPD; (4) severe IVH (Grades III or IV of Papille’s classification);7 (5) cystic periventricular leukomalacia (cystic PVL); (6) necrotizing enterocolitis (NEC; Bell’s criteria ≥2a)8; and (7) NDI (cerebral palsy, cognitive deficit, and vision or hearing impairment).