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Updated: Jun 6, 2026
Biochemical Measurement of Neonatal Hypoxia
Published on: August 24, 2011
Prophylactic methylxanthine for prevention of apnoea in preterm infants
David J Henderson-Smart1, Antonio G De Paoli
1NSW Centre for Perinatal Health Services Research, Queen Elizabeth II Research Institute, Building DO2, University of Sydney, Sydney, NSW, Australia, 2006.
Insights
Prophylactic methylxanthine treatment does not prevent apnoea in preterm infants. While it did not show significant short-term benefits, further research is needed for high-risk infants.
Area of Science:
- Neonatal Medicine
- Pharmacology
- Clinical Trials
Background:
- Recurrent apnoea is a common issue in preterm infants, potentially leading to hypoxemia and bradycardia requiring respiratory support.
- Methylxanthine treatment is effective for managing existing apnoea in infants.
- Prophylactic use of methylxanthines in very preterm infants could potentially prevent apnoea and reduce the need for mechanical ventilation.
Purpose of the Study:
- To evaluate the impact of prophylactic methylxanthine treatment on apnoea, bradycardia, hypoxemia, and mechanical ventilation use in preterm infants.
- To assess the effect on overall morbidity in preterm infants at risk for apnoea of prematurity.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials.
- Searched multiple databases including Cochrane Central Register, MEDLINE, CINAHL, and EMBASE.
- Included trials comparing prophylactic methylxanthine (caffeine or theophylline) with placebo or no treatment in preterm infants.
Main Results:
- Three studies were included; two small trials showed no significant differences in short-term outcomes between prophylactic caffeine and placebo.
- Meta-analysis of two studies found no substantial differences in the use of intermittent positive pressure ventilation (IPPV) or tachycardia.
- A large trial indicated improved survival without developmental disability but prophylactic caffeine subgroup analysis showed no significant clinical outcome differences, except reduced PDA ligation.
Conclusions:
- Current evidence does not support the routine prophylactic use of caffeine for preterm infants at risk of apnoea.
- Future research should focus on high-risk preterm infants, examining outcomes like IPPV, neonatal morbidity, hospital stay, and long-term development.
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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