Key messages
• Caffeine and other similar substances belong to a group of stimulants called methylxanthines. They are often used to prevent and treat apnea – when breathing repeatedly stops and starts – in newborn babies.
• Caffeine may result in little to no difference in the frequency of death in babies born too early compared to other methylxanthines.
• More studies are needed, especially in babies born extremely early, since these babies tend to be the most poorly.
What is apnea of prematurity?
Apnea of prematurity is when babies born too early (preterm babies) stop breathing for 20 seconds or longer during sleep. More than half of all preterm babies have apnea. Preterm babies, especially those born before 28 weeks in the womb (gestation), have a higher risk of death, lung disease, and brain impairment than those born at or near their due date. Some of these babies develop intellectual disabilities, blindness, or deafness.
How is apnea in preterm babies treated?
Apnea in preterm babies is commonly treated with methylxanthines – substances found in high concentrations in tea, coffee, and chocolate. Three types of methylxanthines are caffeine, aminophylline, and theophylline. They act as mild stimulants to speed up the body’s systems and make breathing easier. When given to preterm babies, the aim is to improve their breathing and to reduce apnea episodes and the need for breathing machines (mechanical ventilation).
What did we want to find out?
We wanted to find out if caffeine is better than aminophylline or theophylline in preterm babies for:
• preventing death prior to hospital discharge;
• improving long-term development at age 18 to 24 months of age.
We also wanted to find out if these medicines were associated with any unwanted effects.
What did we do?
We searched for studies that looked at caffeine compared with aminophylline or theophylline in preterm babies. We compared and summarized the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We included 22 studies in our review, with a total of 1776 preterm newborns. Three studies evaluated the use of methylxanthines for apnea prevention; 13 studies evaluated their use for apnea treatment; two for extubation management (that is, removing the tube placed in the windpipe to help a baby breath). In three studies, there were different reasons to treat the babies with methylxanthines. Almost all studies included babies that were born, on average, after 28 to 32 weeks of gestation and with an average weight at birth between 1000 and 1500 grams. No studies had an average length of gestation of less than 28 weeks or an average birth weight of less than 1000 grams. In one study, the babies had an average length of gestation of more than 32 weeks. In two studies, the average birth weight was greater than 1500 grams.
• For the frequency of death, we found that there may be little to no difference between the use of caffeine compared to other methylxanthines.
• When looking at abilities associated with the development of the brain, it is unclear which is the better option: caffeine or other methylxanthines.
• Some babies with apnea episodes develop long-lasting lung disease. Our review indicates that there may be little to no difference between the use of caffeine and other methylxanthines for long-lasting lung disease.
• It is unclear if caffeine results in more unwanted effects compared to other methylxanthines.
• We found that there may be no difference in how long the babies and their families need to stay in the hospital with the use of caffeine compared to other methylxanthines.
What are the limitations of the evidence?
Our confidence in the evidence is limited because the number of babies studied for each outcome we were interested in was small. All babies were randomly placed into groups receiving either caffeine or another methylxanthine (aminophylline or theophylline). However, in many studies, it is possible that staff working with the babies were aware of which treatment the babies were getting. Furthermore, the evidence did not cover all the outcomes we were interested in.
How up to date is this evidence?
The evidence is up to date to February 2023.
