Methylxanthine treatment for apnea in preterm infants [Intervention Review]

Henderson-Smart, David J. and Steer, Peter A. (2008) Methylxanthine treatment for apnea in preterm infants [Intervention Review]. Cochrane Database of Systematic Reviews, 4: CD000140.1-CD000140.19. doi:10.1002/14651858.CD000140

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Author Henderson-Smart, David J.
Steer, Peter A.
Title Methylxanthine treatment for apnea in preterm infants [Intervention Review]
Journal name Cochrane Database of Systematic Reviews   Check publisher's open access policy
ISSN 1469-493X
Publication date 2008-02-05
Year available 2009
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1002/14651858.CD000140
Open Access Status File (Publisher version)
Issue 4
Start page CD000140.1
End page CD000140.19
Total pages 19
Place of publication Oxford, United Kingdom
Publisher John Wiley & Sons
Language eng
Subject 2700 Medicine
2736 Pharmacology (medical)
Formatted 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 that may be severe enough to require resuscitation including use of positive pressure ventilation. Methylxanthines (such as caffeine or theophylline) have been used to stimulate breathing and prevent apnea and its consequences.

Objectives: To determine the effects of methylxanthine treatment on the incidence of apnea and the use of intermittent positive pressure ventilation (IPPV), and other clinically important effects in preterm infants with recurrent apnea.

Search strategy
: Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2007), the Oxford Database of Perinatal Trials, MEDLINE (1966 to January 2008), EMBASE (1982 - January 2008), previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal hand searching mainly in the English language.

Selection criteria: All trials utilizing 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.

Data collection and analysis: Methodological quality was assessed independently by the two review authors. Data were extracted independently by the two review 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).

Main results: The results of five trials that enrolled a total of 192 preterm infants with apnea indicate that methylxanthine therapy leads to a reduction in apnea and use of IPPV in the first two to seven days. There are insufficient data to adequately evaluate side effects and no data to examine effects within different gestational age groups. There are no data in the included studies that examine long-term effects.

Authors' 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. The effects of methylxanthines on long-term outcomes will be addressed in data from the trial awaiting assessment (CAP Trial 2006).

Plain Language Summary
Methylxanthine treatment for apnea in preterm infants
There is some evidence that methylxanthines are effective in the short-term for reducing apnea in premature babies. Apnea is a pause in breathing of greater than 20 seconds. It may occur repeatedly in preterm babies (born before 34 weeks gestation). Methylxanthines (such as theophylline and caffeine) are drugs that are believed to stimulate breathing efforts and have been used to reduce apnea. Adverse effects of feeding intolerance and a rapid heart rate have been found with theophylline. The review of trials found methylxanthines help reduce the number of apnea attacks in the short term. The trials included in this review now have not published longer term out comes, although the general use for a number of indications has been evaluated and outcomes are better in the methylxanthine group. This trial is awaiting assessment.
Keyword Apnea [*prevention & control]
Caffeine [therapeutic use]
Central nervous system stimulants [*therapeutic use]
Infant, newborn
Infant, premature
Infant, premature, diseases [*prevention and control]
Theophylline [therapeutic use]
Vasodilator agents [*therapeutic use]
Xanthines [*therapeutic use]
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: School of Medicine Publications
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