Trends in caffeine use and association between clinical outcomes and timing of therapy in very low birth weight infants

J Pediatr. 2014 May;164(5):992-998.e3. doi: 10.1016/j.jpeds.2013.12.025. Epub 2014 Jan 23.


Objective: To examine the effect of early initiation of caffeine therapy on neonatal outcomes and characterize the use of caffeine therapy in very low birth weight (VLBW) infants.

Study design: We analyzed a cohort of 62 056 VLBW infants discharged between 1997 and 2010 who received caffeine therapy. We compared outcomes in infants receiving early caffeine therapy (initial dose before 3 days of life) and those receiving late caffeine therapy (initial dose at or after 3 days of life) through propensity scoring using baseline and early clinical variables. The primary outcome was the association between the timing of caffeine initiation and the incidence of bronchopulmonary dysplasia (BPD) or death.

Results: We propensity score-matched 29 070 VLBW infants at a 1:1. Of infants receiving early caffeine therapy, 3681 (27.6%) died or developed BPD, compared with 4591 infants (34.0%) receiving late caffeine therapy (OR, 0.74; 99% CI, 0.69-0.80). Infants receiving early caffeine had a lower incidence of BPD (23.1% vs 30.7%; OR, 0.68; 95% CI, 0.63-0.73) and a higher incidence of death (4.5% vs 3.7%; OR, 1.23; 95% CI, 1.05-1.43). Infants receiving early caffeine therapy had less treatment of patent ductus arteriosus (OR, 0.60; 95% CI, 0.55-0.65) and a shorter duration of mechanical ventilation (mean difference, 6 days; P < .001).

Conclusion: Early caffeine initiation is associated with a decreased incidence of BPD. Randomized trials are needed to determine the efficacy and safety of early caffeine prophylaxis in VLBW infants.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural

MeSH terms

  • Bronchopulmonary Dysplasia / epidemiology
  • Bronchopulmonary Dysplasia / prevention & control*
  • Bronchopulmonary Dysplasia / therapy
  • Caffeine / therapeutic use*
  • Central Nervous System Stimulants / therapeutic use*
  • Drug Administration Schedule
  • Ductus Arteriosus, Patent / therapy
  • Female
  • Humans
  • Incidence
  • Infant Mortality*
  • Infant, Newborn
  • Infant, Premature
  • Infant, Very Low Birth Weight*
  • Intensive Care, Neonatal / methods
  • Intensive Care, Neonatal / statistics & numerical data
  • Intensive Care, Neonatal / trends*
  • Male
  • Practice Patterns, Physicians' / statistics & numerical data
  • Practice Patterns, Physicians' / trends*
  • Propensity Score
  • Respiration, Artificial / statistics & numerical data
  • Treatment Outcome
  • United States / epidemiology


  • Central Nervous System Stimulants
  • Caffeine