Systematic review and meta-analysis of clinical outcomes of early caffeine therapy in preterm neonates

Br J Clin Pharmacol. 2017 Jan;83(1):180-191. doi: 10.1111/bcp.13089. Epub 2016 Sep 30.


Aims: This study evaluated the therapeutic outcomes of early versus late caffeine therapy in preterm neonates.

Methods: We performed a systematic literature search in PubMed, Embase, CINAHL and CENTRAL from inception to 30 June 2016 to identify studies investigating the use of early caffeine therapy (initiated at less than 3 days of life) in preterm infants. Effect estimates were combined using random-effects meta-analysis. The primary outcomes for this study were bronchopulmonary dysplasia and mortality.

Results: The initial search found 4066 citations, of which 14 studies enrolling a total of 64 438 participants were included. The time of initiation of early caffeine therapy varied from the first 2 h to 3 days postnatal. Early caffeine therapy reduced the risk of bronchopulmonary dysplasia in both cohort studies (RR: 0.80, 95% CI: 0.66 to 0.96) and randomized controlled trials (RR: 0.67, 95% CI: 0.56 to 0.81). In cohort studies, neonates treated early with caffeine also showed decreased risks of patent ductus arteriosus, brain injury, retinopathy of prematurity and postnatal steroid use. However, the mortality rate was increased.

Conclusions: The findings suggest that early caffeine therapy is associated with reduced incidence of bronchopulmonary dysplasia and may help decrease the burden of morbidities in preterm infants.

Keywords: intensive care; meta-analysis; neonatology; pharmacotherapy; systematic review.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Bronchopulmonary Dysplasia / mortality
  • Bronchopulmonary Dysplasia / prevention & control*
  • Caffeine / administration & dosage*
  • Caffeine / therapeutic use*
  • Early Medical Intervention*
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Caffeine