title: Long-term effects of caffeine therapy for apnea of prematurity.
abstract: 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].).
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. schmidt@mcmaster.ca
authors.forename: Barbara
authors.initials: B
authors.lastname: Schmidt
authors.forename: Robin S
authors.initials: RS
authors.lastname: Roberts
authors.forename: Peter
authors.initials: P
authors.lastname: Davis
authors.forename: Lex W
authors.initials: LW
authors.lastname: Doyle
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Barrington
authors.forename: Arne
authors.initials: A
authors.lastname: Ohlsson
authors.forename: Alfonso
authors.initials: A
authors.lastname: Solimano
authors.forename: Win
authors.initials: W
authors.lastname: Tin
mesh_terms: D001049:Apnea / Q000188:drug therapy* / Q000401:mortality; D049628:Body Size / Q000187:drug effects; D002110:Caffeine / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002547:Cerebral Palsy / Q000453:epidemiology / Q000517:prevention & control; D002951:Citrates / Q000627:therapeutic use*; D002658:Developmental Disabilities / Q000453:epidemiology / Q000517:prevention & control; D004827:Epilepsy / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development; D007235:Infant, Premature, Diseases / Q000188:drug therapy* / Q000401:mortality; D019102:Infant, Very Low Birth Weight / Q000254:growth & development; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D012178:Retinopathy of Prematurity / Q000453:epidemiology; D015996:Survival Rate
chemical_list: D000697:Central Nervous System Stimulants; D002951:Citrates; D002110:Caffeine; C026189:caffeine citrate