Early Caffeine Administration and Neurodevelopmental Outcomes in Preterm Infants

Pediatrics. 2019 Jan;143(1):e20181348. doi: 10.1542/peds.2018-1348. Epub 2018 Dec 5.


Background: Although caffeine use for apnea of prematurity is well studied, the long-term safety and benefit of routine early caffeine administration has not been explored. Our objective was to determine the association between early (within 2 days of birth) versus late caffeine exposure and neurodevelopmental outcomes in preterm infants.

Methods: Infants of <29 weeks' gestation born between April 2009 and September 2011 and admitted to Canadian Neonatal Network units and then assessed at Canadian Neonatal Follow-up Network centers were studied. Neonates who received caffeine were divided into early- (received within 2 days of birth) and late-caffeine (received after 2 days of birth) groups. The primary outcome was significant neurodevelopmental impairment, defined as cerebral palsy, or a Bayley Scales of Infant and Toddler Development, Third Edition composite score of <70 on any component, hearing aid or cochlear implant, or bilateral visual impairment at 18 to 24 months' corrected age.

Results: Of 2108 neonates who were eligible, 1545 were in the early-caffeine group and 563 were in the late-caffeine group. Rates of bronchopulmonary dysplasia, patent ductus arteriosus, and severe neurologic injury were lower in the early-caffeine group than in the late-caffeine group. Significant neurodevelopmental impairment (adjusted odds ratio 0.68 [95% confidence interval 0.50-0.94]) and odds of Bayley Scales of Infant and Toddler Development, Third Edition cognitive scores of <85 (adjusted odds ratio 0.67 [95% confidence interval 0.47-0.95]) were lower in the early-caffeine group than in the late-caffeine group. Propensity score-based matched-pair analyses revealed lower odds of cerebral palsy and hearing impairment only.

Conclusions: Early caffeine therapy is associated with better neurodevelopmental outcomes compared with late caffeine therapy in preterm infants born at <29 weeks' gestation.

Publication types

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

MeSH terms

  • Caffeine / administration & dosage*
  • Canada / epidemiology
  • Central Nervous System Stimulants / administration & dosage*
  • Child Development / drug effects*
  • Child Development / physiology*
  • Cognition / drug effects
  • Cognition / physiology
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Infant, Newborn
  • Infant, Premature / growth & development*
  • Male
  • Retrospective Studies


  • Central Nervous System Stimulants
  • Caffeine