Caffeine has been used for almost 30 years as a respiratory stimulant to reduce the occurrence of apnea of prematurity (AOP) in high-risk infants. New data from Schmidt and colleagues1 published in the New England Journal of Medicine reveal that caffeine may improve survival without neurodevelopmental disability when administered to very low-birth-weight infants. The study provides needed support for a treatment approach that has already become routine clinical practice.2

The study was a large, multicenter, randomized, placebo-controlled trial examining the short- and long-term efficacy and safety of caffeine therapy for AOP. Infants were randomized to receive a loading dose of 20 mg/kg of caffeine followed by a daily maintenance dose of 5 mg/kg or to placebo. Neurodevelopmental evaluation was conducted at 18 to 21 months' corrected age. The primary outcome was death before a corrected age of 18 months or survival with one or more of the following: cerebral palsy, cognitive delay, hearing loss requiring amplification, and bilateral blindness.1

Caffeine reduced the incidences of cerebral palsy and cognitive delay but had no significant effects on the rates of death, severe hearing loss, or bilateral blindness.1 Of the 937 infants who received caffeine, 377 (40.2%) died or survived with a neurodevelopmental disability, compared with 431 (46.2%) of the 932 children in the placebo group. The number needed to treat was 16 to prevent one adverse outcome at 18 months. Growth, as indexed by height, weight, and head circumference, was not affected by caffeine treatment.1

One possible mechanism for the effect of caffeine, suggested study authors, was improvement in respiratory function. Earlier discontinuation of positive airway pressure in infants assigned to caffeine, as compared with placebo, explained approximately half of the effect of caffeine on the 18-month outcome.

References