Early Caffeine Administration and Neurodevelopmental Outcomes in Preterm Infants

Abstract

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.