Optimizing Caffeine Use and Risk of Bronchopulmonary Dysplasia in Preterm Infants A Systematic Review, Meta-analysis, and Application of Grading of Recommendations Assessment, Development, and Evaluation Methodology

Caffeine reduces the risk of bronchopulmonary dysplasia (BPD). Optimizing caffeine use could increase therapeutic benefit. The authors performed a systematic review and random-effects meta-analysis of studies comparing different timing of initiation and dose of caffeine on the risk of BPD. Earlier initiation, compared with later, was associated with a decreased risk of BPD (5 observational studies; n = 63,049; adjusted OR, 0.69; 95% CI, 0.64-0.75; GRADE, low quality). High-dose caffeine, compared with standard dose, was associated with a decreased risk of BPD (3 randomized trials; n = 432; OR, 0.65; 95% CI, 0.43-0.97; GRADE, low quality). Higher-quality evidence is needed to guide optimal caffeine use.