What are the benefits and risks of medicines that stimulate breathing (such as caffeine) for the prevention or treatment of low oxygen levels or breathing problems in babies born a few weeks early?

Key messages

• Only one study looked at whether giving medicines that stimulate breathing, like caffeine, to babies born a few weeks early can help prevent or reduce problems with low oxygen levels or breathing. This means that we have very little evidence about their use.

• Caffeine may help reduce the number of times late preterm babies have low oxygen levels, but we do not know if it reduces the need for breathing (respiratory) support (such as ventilators); and we are not sure if caffeine causes unwanted effects.

• More research is needed to know if medicines that stimulate breathing are helpful and safe for babies born a few weeks early. We found some studies that will be published soon that will help to update the evidence.

How old are late preterm babies?

Babies born a few weeks early, between 34 and 36 weeks of pregnancy, are called ‘late preterm’. These babies are not as fully developed as babies born at full term (after 37 weeks, or 8.5 months), and their lungs and other organs may be weaker.

What is intermittent hypoxemia?

Sometimes, a person's oxygen levels can drop for short periods of time (a condition called intermittent hypoxia). When this happens, it is difficult to breathe. Breathing difficulties can cause long-term problems by damaging the brain.

What are methylxanthines?

Methylxanthines are medicines which make breathing easier by relaxing the muscles we use to breathe. Caffeine is the most commonly used type of methylxanthine because it has fewer unwanted effects than other types.

What did we want to find out?

Although methylxanthines like caffeine are often used, successfully, to treat breathing problems in very early (premature) babies (born before 32 weeks of pregnancy), they are used less often in late preterm babies, and it is not clear if this treatment can help them. We wanted to know if methylxanthines are better than no treatment or a dummy treatment (placebo) for preventing or treating problems with low oxygen levels or breathing in late preterm babies. We also wanted to know if these medicines cause any unwanted effects.

What did we do?

We searched for studies that compared methylxanthines with placebo or no treatment in late preterm babies. We looked for studies that measured:

• how often babies had low oxygen levels;

• whether they needed help to breathe;

• how long they stayed in the hospital;

• if the treatment had any unwanted effects;

• if the babies survived until leaving the hospital.

We looked at the results of the only study we found. We summarized the results, and rated our confidence in the evidence based on factors such as the number of babies in the study (study size), and methods used when conducting the study.

What did we find?

We found one study from New Zealand with 132 late preterm babies. The study compared different doses of caffeine with a placebo and had the following results.

• Caffeine may reduce the number of times babies have low oxygen levels over one week from starting treatment.

• It is not clear if caffeine helps with other problems, like needing help to breathe, or improves the chances of being able to leave hospital earlier or surviving until leaving the hospital.

• It is not clear if caffeine causes unwanted effects.

• The study did not report on other important outcomes, like long-term development or the number of times a baby stopped breathing (apnea).

We found no studies that looked at using methylxanthines to treat, rather than prevent, breathing problems in these babies.

What are the limitations of the evidence?

The biggest limitation is that we only found one study. This means we cannot be sure about the results. The study did not report on all the outcomes we wanted to know about, and some results were not clear. Our confidence in these findings is very low because they are based on only one small study, and we had some concerns about how the study was carried out and reported. Future research may change these results.

How up to date is this evidence?

The evidence is current to December 2025. There are five studies in progress and when they are complete, their results may help us better understand if methylxanthines are helpful and safe for late preterm babies.