title: Methylxanthine treatment for apnea in preterm infants.
abstract: BACKGROUND
  Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Methylxanthines have been used to stimulate breathing and prevent apnea and its consequences.
  
  
  OBJECTIVE
  The objective of this review is to determine if methylxanthine treatment in preterm infants with recurrent apnea leads to a clinically important reduction in apnea and use of intermittent positive pressure ventilation (IPPV), without clinically important side effects.
  
  
  METHODS
  Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts of conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language.
  
  
  METHODS
  All trials utilising random or quasi-random patient allocation, in which methylxanthine (theophylline or caffeine) was compared with placebo or no treatment for apnea in preterm infants, were included.
  
  
  METHODS
  Methodological quality was assessed independently by the two authors. Data were extracted independently by the two authors. Treatment effects were expressed as relative risk (RR) and risk difference (RD) and their 95% confidence intervals, using a fixed effect model. For significant results, the inverse of the risk difference (1/RD) was used to calculate the number needed to treat (NNT).
  
  
  RESULTS
  The results of four trials which enrolled a total of 110 preterm infants with apnea indicate that methylxanthine therapy leads to a reduction in apnea and use of IPPV in the first 2 - 7 days. There are insufficient data to evaluate side effects and no data to examine effects within different gestational age groups. There are no trial data which examine long term effects.
  
  
  CONCLUSIONS
  Methylxanthines are effective in reducing the number of apneic attacks and the use of mechanical ventilation in the two to seven days after starting treatment. In view of its lower toxicity, caffeine would be the preferred drug. Although the safety of methylxanthine therapy has been suggested in cohort studies, there are no trial data on longterm outcome. In order to indicate which infants are likely to benefit from treatment, there is a need for stratification by gestation and/or other risk factors in future studies. In any future studies the longer term effects of treatment on growth and development should be evaluated.
authors.affiliation: NSW Centre for Perinatal Health Services Research, Queen Elizabeth II Institute for Mothers and Infants, Building DO2, University of Sydney, Sydney, NSW, Australia, 2006. dhs@mail.usyd.edu.au
authors.forename: D J
authors.initials: DJ
authors.lastname: Henderson-Smart
authors.forename: P
authors.initials: P
authors.lastname: Steer
mesh_terms: D001049:Apnea / Q000517:prevention & control*; D002110:Caffeine / Q000627:therapeutic use; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000517:prevention & control*; D013806:Theophylline / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000627:therapeutic use*; D014970:Xanthines / Q000627:therapeutic use*
chemical_list: D000697:Central Nervous System Stimulants; D014665:Vasodilator Agents; D014970:Xanthines; C008514:methylxanthine; D002110:Caffeine; D013806:Theophylline