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

Early Caffeine Administration and Neurodevelopmental Outcomes in Preterm Infants.

Author information

Departments of Pediatrics and
Community Health Sciences and.
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
University of Alberta, Edmonton, Alberta, Canada.
Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
Departments of Pediatrics and.
Sainte Justine University Health Center, University of Montreal, Montreal, Quebec, Canada.
Maternal-Infant Care Research Center, Mount Sinai Hospital, Toronto, Ontario, Canada.
Department of Pediatrics, Sinai Health System, Toronto, Ontario, Canada; and.
Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.



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.


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.


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.


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


Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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