The Most Common Medicine in the NICU — and What We Really Know About It
A plain-language look at a 2024 review that combined 15 studies of caffeine in premature babies to ask what it truly does
Caffeine is one of the most common medicines given to premature babies, used for decades to help them breathe. A large 2024 review that combined 15 trials and 3,530 infants found that caffeine probably reduces chronic lung disease and a common heart-vessel problem, and is linked to better movement skills later in childhood — though much of the evidence is less certain than its everyday use might suggest [1].
Why This Matters for Families
If your baby was born early and spent time in a neonatal intensive care unit (NICU), there is a good chance they received caffeine. It is the same caffeine found in coffee, given in carefully measured doses. Premature babies often have a breathing problem called apnea of prematurity, in which the baby's immature brain occasionally "forgets" to breathe for short periods, sometimes with a slowing heart rate or a dip in oxygen [2]. Caffeine gently stimulates the part of the brain that controls breathing, which is why it has been a NICU staple for many years. Because it is so widely used, it is worth understanding what the science actually shows — and, just as importantly, where the science is still uncertain.
The Problem That Started It All
Before caffeine, doctors had few good options for these breathing pauses. In the 1970s, researchers showed that caffeine could reduce apnea in small babies, and it gradually became standard care because it was easy to give — usually just once a day — and did not require frequent blood tests [3]. For about thirty years, that was largely the whole story: caffeine reduced the visible breathing pauses, so it was used. But a question lingered. Did caffeine only help in the short term, or did it actually change how these children turned out years later? Families and doctors had no firm answer, and the long-term consequences of being born early can be significant [4].
Caffeine's long journey through newborn care — from a simple breathing aid to a medicine studied for its possible effects on the developing brain — has been described by doctors who trace its history in the NICU [5]. That history matters, because it explains why caffeine became so deeply routine before some of the hardest questions about it were ever formally answered.
That changed with a landmark study called the CAP trial, which followed more than 2,000 very small babies. It found that caffeine reduced a serious chronic lung condition [6] and that, by around 18 months to 2 years of age, more caffeine-treated children were alive and free of disability [7]. Some of that early advantage faded by age 5 [8], but a benefit for movement and coordination could still be seen at age 11 [9]. These results transformed caffeine from a simple breathing aid into something many believed might actually protect the developing brain.
What the New Review Did
A research team in New Zealand wanted to step back and look at all the trustworthy evidence at once. They gathered every well-designed study (called a randomised controlled trial) comparing caffeine with a dummy treatment, or comparing a higher dose with a lower dose, in babies born before 37 weeks. They found 15 such studies, involving 3,530 premature infants, and combined the results — a method that gives a clearer overall picture than any single study. They also rated how confident we can be in each finding, which is what makes this review especially useful [1].
What They Found
The most dependable good news was about two things other than breathing. Caffeine probably reduces chronic lung disease, and it probably reduces a common heart-blood-vessel problem (a patent ductus arteriosus) that sometimes needs treatment in premature babies [1]. For these two benefits, the evidence was reasonably solid.
Here is the surprising part. The evidence that caffeine reduces apnea itself — the very reason it is usually prescribed — was rated as very uncertain. The studies pointed in caffeine's favour, but they were small, defined apnea in different ways, and had weaknesses that made the overall conclusion shaky [1]. This does not mean caffeine does not help with breathing pauses; experienced doctors see that it often does. It means the formal proof is weaker than its everyday use would lead you to expect.
On long-term development, the news was cautiously positive but came almost entirely from that one CAP study. By the early school years, caffeine-treated children appeared to have somewhat better thinking skills and clearly better movement skills [9]. Because this rests on a single group of children, it applies most confidently to babies like those in that trial — the smallest and earliest-born.
The Dose Question
Some NICUs have moved toward giving higher doses of caffeine. The review found that higher doses probably reduce chronic lung disease a bit more than lower doses, and may calm breathing pauses slightly more [1]. But higher doses also more than doubled the chance of a fast heart rate [1]. And importantly, no study has checked whether higher doses are just as safe for long-term brain development. So while higher doses look helpful for the lungs in the short term, the long-term safety of that choice has simply not been tested yet [1].
Is Caffeine Safe?
Caffeine has a long record of being well tolerated in newborns, which is part of why it became so widely used. The main side effect the review identified was a faster heart rate, and this was seen mostly with the higher doses [1]. A faster heart rate is something NICU teams watch for closely, because babies are already monitored continuously, and it can usually be managed by adjusting the dose. The review did not find evidence that caffeine causes serious harm, but it is honest about the limits of what we know: many of the studies were small, and the long-term safety of the higher doses in particular has not been fully tested [1]. This is why thoughtful teams aim to use the lowest dose that achieves the goal, and to keep watching how each baby responds.
It also helps to understand why doctors care so much about these breathing pauses in the first place. Research has shown that frequent dips in oxygen and slowing of the heart in very premature babies are linked to a higher chance of problems later on [2]. That is the worry caffeine is meant to address — not just the breathing pauses you can see on the monitor, but the possible long-term effects of those repeated dips. Seen this way, caffeine is part of a larger effort to protect a baby's development during a vulnerable window, even though, as this review shows, the proof that it fully succeeds is still being gathered.
What This Means for Your Baby
If your baby received caffeine, this review is reassuring overall: it is a medicine with probable real benefits and a long track record. The honest summary doctors can offer is that caffeine probably helps the lungs and is linked to better movement outcomes, that it is generally well tolerated, but that the ideal dose is still unknown and much of the evidence is less certain than its routine use suggests. These are not reasons for worry — they are reasons for the careful, individualized decisions good NICU teams already make. It is always reasonable to ask your baby's team why caffeine is being used, at what dose, and how your baby is being monitored.
What Researchers Are Working On Next
The review points clearly to what is needed. Scientists are calling for larger studies that test different doses and then follow the children for years, not just weeks, to be sure higher doses are safe for the brain as well as the lungs [1]. They also want to learn whether babies born at different stages of prematurity — including those born only a few weeks early, who can also have breathing dips [10] — benefit in the same way, a question a recent dosing study has begun to explore [11]. Until those answers arrive, caffeine remains a trusted and probably beneficial part of newborn care, used thoughtfully by teams who, like the researchers, are committed to learning more.
References
- Oliphant EA, Hanning SM, McKinlay CJD, Alsweiler JM. Caffeine for apnea and prevention of neurodevelopmental impairment in preterm infants: systematic review and meta-analysis. Journal of Perinatology. 2024;44(6):785–801. doi:10.1038/s41372-024-01939-x ↩
- Poets CF, Roberts RS, Schmidt B, et al. Association between intermittent hypoxemia or bradycardia and late death or disability in extremely preterm infants. JAMA. 2015;314(6):595–603. doi:10.1001/jama.2015.8841 ↩
- Aranda JV, Gorman W, Bergsteinsson H, Gunn T. Efficacy of caffeine in treatment of apnea in the low-birth-weight infant. J Pediatr. 1977;90(3):467–72. doi:10.1016/S0022-3476(77)80718-X80718-X) ↩
- Moster D, Lie RT, Markestad T. Long-term medical and social consequences of preterm birth. N Engl J Med. 2008;359(3):262–73. doi:10.1056/NEJMoa0706475 ↩
- Muehlbacher T, Gaertner VD, Bassler D. History of caffeine use in neonatal medicine and the role of the CAP trial. Semin Fetal Neonatal Med. 2020;25(6):101159. doi:10.1016/j.siny.2020.101159 ↩
- Schmidt B, Roberts RS, Davis P, et al. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006;354(20):2112–21. doi:10.1056/NEJMoa054065 ↩
- Schmidt B, Roberts RS, Davis P, et al. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med. 2007;357(19):1893–902. doi:10.1056/NEJMoa073679 ↩
- Schmidt B, Anderson PJ, Doyle LW, et al. Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity. JAMA. 2012;307(3):275–82. doi:10.1001/jama.2011.2024 ↩
- Schmidt B, Roberts RS, Anderson PJ, et al. Academic performance, motor function, and behavior 11 years after neonatal caffeine citrate therapy for apnea of prematurity. JAMA Pediatr. 2017;171(6):564–72. doi:10.1001/jamapediatrics.2017.0238 ↩
- Williams LZJ, McNamara D, Alsweiler JM. Intermittent hypoxemia in infants born late preterm: a prospective cohort observational study. J Pediatr. 2018;204:89–95.e1. doi:10.1016/j.jpeds.2018.08.048 ↩
- Oliphant EA, McKinlay CJD, McNamara D, Cavadino A, Alsweiler JM. Caffeine to prevent intermittent hypoxaemia in late preterm infants: randomised controlled dosage trial. Arch Dis Child Fetal Neonatal Ed. 2023;108(2):106–13. doi:10.1136/archdischild-2022-324010 ↩