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Meta-Analysis
. 2010 Dec 8;2010(12):CD000432.
doi: 10.1002/14651858.CD000432.pub2.

Prophylactic methylxanthine for prevention of apnoea in preterm infants

David J Henderson-Smart  1 , Antonio G De Paoli
Affiliations
Meta-Analysis

Prophylactic methylxanthine for prevention of apnoea in preterm infants

David J Henderson-Smart et al. Cochrane Database Syst Rev. .

Abstract

Background: Recurrent apnoea is common in preterm infants. These episodes can lead to hypoxaemia and bradycardia, which may be severe enough to require the use of positive pressure ventilation. In infants with apnoea, methylxanthine treatment has been used successfully to prevent further episodes. It is possible that prophylactic therapy given to all very preterm infants soon after birth might prevent apnoea and the need for additional ventilator support.

Objectives: To determine the effect of prophylactic treatment with methylxanthine on apnoea, bradycardia, episodes of hypoxaemia, use of mechanical ventilation, and morbidity in preterm infants at risk for apnoea of prematurity

Search strategy: The standard search strategy of the Neonatal Review Group was updated in August 2010. This included searches of the Cochrane Central Register of Controlled Trials, Oxford Database of Perinatal Trials, MEDLINE, CINAHL and EMBASE.

Selection criteria: All trials using random or quasi-random patient allocation in which prophylactic methylxanthine (caffeine or theophylline) was compared with placebo or no treatment in preterm infants were eligible.

Data collection and analysis: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used.

Main results: Three studies were eligible for inclusion in the review. Two small studies (randomising a total of 104 infants) evaluated the effect of prophylactic caffeine on short term outcomes. There were no meaningful differences between the caffeine and placebo groups in the number of infants with apnoea, bradycardia, hypoxaemic episodes, use of IPPV or side effects in either of the studies. Only two outcomes (use of IPPV and tachycardia) were common to the two studies and meta-analysis showed no substantive differences between the groups. One large trial of caffeine therapy (CAP 2006) in a heterogeneous group of infants at risk for and having apnoea of prematurity demonstrated an improved rate of survival without developmental disability at 18 to 21 months corrected age. The reports of the subgroup of infants treated with prophylactic caffeine did not demonstrate any significant differences in clinical outcomes except for a decrease in the risk of PDA ligation.

Authors' conclusions: The results of this review do not support the use of prophylactic caffeine for preterm infants at risk of apnoea.Any future studies need to examine the effects of prophylactic methylxanthines in preterm infants at higher risk of apnoea. This should include examination of important clinical outcomes such as need for IPPV, neonatal morbidity, length of hospital stay and long term development.

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Conflict of interest statement

None

Figures

1.1
1.1. Analysis
Comparison 1 All infants, Outcome 1 Apnea (more than 4/day).
1.2
1.2. Analysis
Comparison 1 All infants, Outcome 2 Apnea (more than 10/day).
1.3
1.3. Analysis
Comparison 1 All infants, Outcome 3 Bradycardia (more than 12/day).
1.4
1.4. Analysis
Comparison 1 All infants, Outcome 4 Bradycardia (more than 24/day).
1.5
1.5. Analysis
Comparison 1 All infants, Outcome 5 Hypoxemic episodes (more than 12/day).
1.6
1.6. Analysis
Comparison 1 All infants, Outcome 6 Withdrawal for definitive caffeine treatment.
1.7
1.7. Analysis
Comparison 1 All infants, Outcome 7 Use of IPPV.
1.8
1.8. Analysis
Comparison 1 All infants, Outcome 8 Tachycardia.
1.9
1.9. Analysis
Comparison 1 All infants, Outcome 9 Hyponatremia.
1.10
1.10. Analysis
Comparison 1 All infants, Outcome 10 PDA ligation.
1.11
1.11. Analysis
Comparison 1 All infants, Outcome 11 PMA at last oxygen therapy.
1.12
1.12. Analysis
Comparison 1 All infants, Outcome 12 PMA at last endotracheal tube.
1.13
1.13. Analysis
Comparison 1 All infants, Outcome 13 PMA at last positive pressure ventilation.
1.14
1.14. Analysis
Comparison 1 All infants, Outcome 14 Bronchopulmonary dysplasia at term.
1.15
1.15. Analysis
Comparison 1 All infants, Outcome 15 Cognitive delay.
1.16
1.16. Analysis
Comparison 1 All infants, Outcome 16 Cerebral palsy.
1.17
1.17. Analysis
Comparison 1 All infants, Outcome 17 Death or major disability.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Bucher 1988 {published and unpublished data}
    1. Bucher HU, Duc G. Does caffeine prevent hypoxaemic episodes in premature infants? A randomized controlled trial. European Journal of Pediatrics 1988;147:288‐91. - PubMed
CAP 2006 {published data only}
    1. Davis PG, Schmidt B, Roberts RS, Doyle LW, Asztalos E, Haslam R, Sinha S, Tin W, Caffeine for Apnea of Prematurity Trial Group. Caffeine for Apnea of Prematurity Trial: benefits may vary in subgroups. Journal of Pediatrics 2010;156:382‐7. - PubMed
    1. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W, Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. New England Journal of Medicine 2006;354:2112‐21. - PubMed
    1. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W, Caffeine for Apnea of Prematurity Trial Group. Long‐term effects of caffeine therapy for apnea of prematurity. New England Journal of Medicine 2007;357:1893‐902. - PubMed
Levitt 1988 {published and unpublished data}
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References to studies excluded from this review

Larsen 1995 {published data only}
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Additional references

AAP 2003
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Blanchard 1992
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Henderson‐Smart 2008a
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Henderson‐Smart 2009
    1. Henderson‐Smart DJ, Peter Steer. Methylxanthine treatment for apnea in preterm infants. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD000140] - DOI
Henderson‐Smart 2010
    1. Henderson‐Smart DJ, Steer P. Caffeine vs theophylline treatment for apnea in preterm infants. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD000273] - DOI
Samuels 1992
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References to other published versions of this review

Henderson‐Smar 2009
    1. Henderson‐Smart DJ, Steer PA. Prophylactic methylxanthine for prevention of apnea in preterm infants. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD000432] - PubMed
Henderson‐Smart 1999
    1. Henderson‐Smart DJ, Steer PA. Prophylactic methylxanthine for prevention of apnea in preterm infants. Cochrane Database of Systematic Reviews 1999, Issue 2. [DOI: 10.1002/14651858.CD000432] - DOI - PubMed
Henderson‐Smart 2002
    1. Henderson‐Smart DJ, Steer PA. Prophylactic methylxanthine for prevention of apnea in preterm infants. Cochrane Database of Systematic Reviews 2002, Issue 2. [DOI: 10.1002/14651858.CD000432] - DOI - PubMed
Henderson‐Smart 2006
    1. Henderson‐Smart DJ, Steer PA. Prophylactic methylxanthine for prevention of apnea in preterm infants. Cochrane Database of Systematic Reviews 2006, Issue 2. [DOI: 10.1002/14651858.CD000432] - DOI - PubMed

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