Administration time of caffeine in preterm infants: systematic review and meta-analysis.

To assess the ideal time for caffeine administration in preterms, identifying its effects and safety. Study Design: Meta-analysis conducted including preterms <32 weeks GA or BW < 1500 g, comparing caffeine administration time: <24 x ≥24HOL, <48 x ≥48HOL, <72 x ≥72HOL. 18 studies included 76.998 patients. The median age of starting caffeine was the first 24 HOL. In the overall comparisons, there was reduction in patent ductus arteriosus (OR 0.71 [0.55, 0. 92]; low evidence), retinopathy of prematurity (OR 0.71 [0.54, 0.93]; moderate evidence), severe brain injury (OR 0.79 [0.70, 0.91]; moderate evidence), bronchopulmonary dysplasia (BPD) (OR 0.69 [0.59, 0.81]; moderate evidence), composite outcome of BPD or death (OR 0.76 [0.66, 0.88]; moderate evidence). Mortality increase was found (OR 1.20 [1.12, 1.29], very low evidence).Caffeine in the first 24 HOL has benefits in reducing morbidities associated with prematurity. Mortality finding is potentially due to survival bias.