Association of early caffeine administration and neonatal outcomes in very preterm neonates

JAMA Pediatr. 2015 Jan;169(1):33-8. doi: 10.1001/jamapediatrics.2014.2223.


Importance: Advantages of caffeine for apnea of prematurity have prompted clinicians to use it prophylactically even before apnea.

Objective: To determine the effect of early initiation of caffeine therapy on neonatal outcomes in very preterm infants born in Canada.

Design, setting, and participants: A retrospective cohort study was conducted. Patients included preterm neonates born at less than 31 weeks' gestation admitted to 29 participating Canadian Neonatal Network neonatal intensive care units between January 1, 2010, and December 31, 2012.

Exposures: Neonates who received caffeine were divided into 2 groups based on the following timing of caffeine initiation: within the first 2 days after birth (early) and on or after the third day following birth (late).

Main outcome and measure: A composite of death or bronchopulmonary dysplasia.

Results: Of 5517 eligible neonates, 5101 (92.5%) received caffeine (early: 3806 [74.6%]; late: 1295 [25.4%]). There was no difference in weight or gestational age at birth between the groups. Neonates in the early group had decreased odds of a composite outcome of death or bronchopulmonary dysplasia (adjusted odds ratio [AOR], 0.81; 95% CI, 0.67-0.98) and patent ductus arteriosus (AOR, 0.74; 95% CI, 0.62-0.89). There was no difference between the groups in mortality (AOR, 0.98; 95% CI, 0.70-1.37), necrotizing enterocolitis (AOR, 0.88; 95% CI, 0.65-1.20), severe neurological injury (AOR, 0.80; 95% CI, 0.63-1.01), or severe retinopathy of prematurity (AOR, 0.78; 95% CI, 0.56-1.10).

Conclusions and relevance: In very preterm neonates, early (prophylactic) caffeine use was associated with a reduction in the rates of death or bronchopulmonary dysplasia and patent ductus arteriosus. No adverse impact on any other outcomes was observed.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apnea / mortality
  • Apnea / prevention & control*
  • Bronchopulmonary Dysplasia / mortality
  • Bronchopulmonary Dysplasia / prevention & control*
  • Caffeine / administration & dosage*
  • Canada / epidemiology
  • Ductus Arteriosus, Patent / mortality
  • Ductus Arteriosus, Patent / prevention & control*
  • Gestational Age
  • Humans
  • Infant
  • Infant Mortality
  • Infant, Extremely Premature
  • Infant, Newborn
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome


  • Caffeine