High-versus low-dose caffeine in preterm infants: a systematic review and meta-analysis

Aim Though caffeine is a consolidated treatment in preterm infants, the efficacy and safety of a higher dose have not been systematically appraised. Methods A systematic review was conducted to compare high (loading dose >20 mg/kg and maintenance >10 mg/kg/day) versus low dose of caffeine. MEDLINE, EMBASE, Central and conference proceedings for randomised controlled trials (RCTs) and quasi-RCTs were searched. Two authors independently screened the records, extracted the data and assessed the risk of bias. Results As only six RCTs enrolling a total of 816 preterm infants were included, the required information size was not reached. The loading and maintenance doses varied between 20 and 80 mg/kg/day and 3 and 20 mg/kg/day, respectively. The use of high dose had no impact on mortality (RR: 0.85; 95% CI: 0.53-1.38; RCTs = 4). However, it resulted in fewer cases of extubation failure, apnoeas and bronchopulmonary dysplasia (RR: 0.76; 95% CI: 0.60-0.96; studies = 4) and shorter duration of mechanical ventilation. The quality of the evidence was low due to imprecision of the estimates. Conclusion Due to imprecision, it is not possible to determine whether high-dose caffeine is more effective and safe than a low dose. High dose might improve short-term respiratory function and reduce bronchopulmonary dysplasia.