Caffeine therapy for apnea of prematurity

N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056/NEJMoa054065.

Abstract

Background: Methylxanthines reduce the frequency of apnea of prematurity and the need for mechanical ventilation during the first seven days of therapy. It is uncertain whether methylxanthines have other short- and long-term benefits or risks in infants with very low birth weight.

Methods: We randomly assigned 2006 infants with birth weights of 500 to 1250 g during the first 10 days of life to receive either caffeine or placebo, until drug therapy for apnea of prematurity was no longer needed. We evaluated the short-term outcomes before the first discharge home.

Results: Of 963 infants who were assigned to caffeine and who remained alive at a postmenstrual age of 36 weeks, 350 (36 percent) received supplemental oxygen, as did 447 of the 954 infants (47 percent) assigned to placebo (adjusted odds ratio, 0.63; 95 percent confidence interval, 0.52 to 0.76; P<0.001). Positive airway pressure was discontinued one week earlier in the infants assigned to caffeine (median postmenstrual age, 31.0 weeks; interquartile range, 29.4 to 33.0) than in the infants in the placebo group (median postmenstrual age, 32.0 weeks; interquartile range, 30.3 to 34.0; P<0.001). Caffeine reduced weight gain temporarily. The mean difference in weight gain between the group receiving caffeine and the group receiving placebo was greatest after two weeks (mean difference, -23 g; 95 percent confidence interval, -32 to -13; P<0.001). The rates of death, ultrasonographic signs of brain injury, and necrotizing enterocolitis did not differ significantly between the two groups.

Conclusions: Caffeine therapy for apnea of prematurity reduces the rate of bronchopulmonary dysplasia in infants with very low birth weight. (ClinicalTrials.gov number, NCT00182312.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apnea / drug therapy*
  • Apnea / therapy
  • Bronchopulmonary Dysplasia / prevention & control*
  • Caffeine / pharmacology
  • Caffeine / therapeutic use*
  • Central Nervous System Stimulants / pharmacology
  • Central Nervous System Stimulants / therapeutic use*
  • Combined Modality Therapy
  • Female
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / drug therapy*
  • Infant, Very Low Birth Weight*
  • Logistic Models
  • Male
  • Oxygen Inhalation Therapy
  • Respiration, Artificial*
  • Weight Gain / drug effects

Substances

  • Central Nervous System Stimulants
  • Caffeine

Associated data

  • ClinicalTrials.gov/NCT00182312