Long-Term Effects of Caffeine Therapy for Apnea of Prematurity Journal Articles uri icon

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  • BACKGROUND: Methylxanthine therapy is commonly used for apnea of prematurity but in the absence of adequate data on its efficacy and safety. It is uncertain whether methylxanthines have long-term effects on neurodevelopment and growth. METHODS: We randomly assigned 2006 infants with birth weights of 500 to 1250 g to receive either caffeine or placebo until therapy for apnea of prematurity was no longer needed. The primary outcome was a composite of death, cerebral palsy, cognitive delay (defined as a Mental Development Index score of <85 on the Bayley Scales of Infant Development), deafness, or blindness at a corrected age of 18 to 21 months. RESULTS: Of the 937 infants assigned to caffeine for whom adequate data on the primary outcome were available, 377 (40.2%) died or survived with a neurodevelopmental disability, as compared with 431 of the 932 infants (46.2%) assigned to placebo for whom adequate data on the primary outcome were available (odds ratio adjusted for center, 0.77; 95% confidence interval [CI], 0.64 to 0.93; P=0.008). Treatment with caffeine as compared with placebo reduced the incidence of cerebral palsy (4.4% vs. 7.3%; adjusted odds ratio, 0.58; 95% CI, 0.39 to 0.87; P=0.009) and of cognitive delay (33.8% vs. 38.3%; adjusted odds ratio, 0.81; 95% CI, 0.66 to 0.99; P=0.04). The rates of death, deafness, and blindness and the mean percentiles for height, weight, and head circumference at follow-up did not differ significantly between the two groups. CONCLUSIONS: Caffeine therapy for apnea of prematurity improves the rate of survival without neurodevelopmental disability at 18 to 21 months in infants with very low birth weight. (ClinicalTrials.gov number, NCT00182312 [ClinicalTrials.gov].).


  • Schmidt, Barbara
  • Roberts, Robin Sydney
  • Davis, Peter
  • Doyle, Lex W
  • Barrington, Keith J
  • Ohlsson, Arne
  • Solimano, Alfonso
  • Tin, Win

publication date

  • November 8, 2007

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