When Caffeine Is Not Enough: How European Hospitals Care for Babies Whose Breathing Pauses, and What Researchers Hope to Do Better

Two 2025 papers, a survey of 447 European neonatal units (Lavizzari et al.) and a review of tailoring drug treatment to each baby (Fatunla et al.), explained for families

Many babies born very early pause their breathing for a few seconds because the brain's breathing controls are not yet mature, and almost all of them are given caffeine to help. A large European survey shows that hospitals agree closely on caffeine but differ on what comes next, and a second paper explains why babies may need different treatment and how it might one day be tailored to each one.

What are "apnoea of prematurity" and why does it happen?

Apnoea (pronounced "ap-nee-a") simply means a pause in breathing. In babies born early, the part of the brain that sets the rhythm of breathing is still developing, so breathing can stop for 15 to 20 seconds or longer. Doctors call this "apnoea of prematurity". It is very common: the review by Fatunla and colleagues notes that it affects roughly nine in ten babies born weighing less than 1,000 g, and more than half of those born before 32 weeks of pregnancy ^[1]. During a pause, the heart rate can slow (bradycardia) and the oxygen level in the blood can dip (desaturation). The monitors on the neonatal intensive care unit (NICU) are there to catch exactly this, which is why alarms are a normal part of life on the unit. The care team may gently stroke or tap the baby to remind them to breathe, and breathing often restarts. This kind of immaturity is a recognised, well-described condition, covered in a clinical report by the American Academy of Pediatrics ^[2].

How doctors came to rely on caffeine

Caffeine, the same substance found in coffee, has been used in newborn care for more than 40 years because it stimulates the brain's breathing centres ^[1]. Strong proof of its value came from the Caffeine for Apnea of Prematurity (CAP) trial, a large international study that included 2006 very small babies. Half received caffeine and half received a dummy medicine (a placebo). Babies given caffeine needed breathing support for about a week less and were less likely to develop long-term lung disease ^[3]. When the children were 18 to 21 months old, those who had received caffeine were somewhat less likely to have died or developed a disability (about 40 in 100 compared with 46 in 100) ^[4]. By age 11, the picture was more mixed: overall difficulties were not clearly different, though problems with movement were less common ^[5].

Since then, families and doctors have faced a set of practical questions that the trial did not settle: when to start, what dose to give, and when to stop. A large trial of extending caffeine in moderately early babies, called the MoCHA trial (run in 29 US hospitals), did not shorten hospital stays ^[6]. A review of the evidence on stopping suggests that waiting until a baby's symptoms have settled, rather than stopping at a fixed age, may mean fewer drops in oxygen ^[7]. For babies who still have pauses despite caffeine, doctors may add a second medicine called doxapram, which stimulates breathing in a different way. But a systematic review concluded that its routine use could not be recommended because good trials were lacking ^[8], and a later review of the trials by the Cochrane collaboration (an independent group that pools trial results) found that the evidence remained weak ^[9].

Two papers, two different views

This article looks at two research papers published a few months apart in 2025. They were written by different teams and do not refer to each other, so they are best seen as two pieces of one puzzle. The first, by Lavizzari and colleagues, is a survey: researchers e-mailed a lead doctor in each of 721 NICUs across 24 European countries, and 447 units (about six in ten) answered ^[10]. The survey tells us what units say they do. The second, by Fatunla and colleagues, is a review article, in which experts discuss the research that already exists. It does not report a new experiment; it explains how the medicines work and why one standard dose may not suit every baby ^[1].

What the survey found

Every unit used caffeine, and the typical doses were very similar from place to place. About three in four stopped caffeine when babies reached 34 to 35 weeks of "postmenstrual age" (which means weeks of pregnancy at birth plus weeks since birth) ^[10]. Most units gave caffeine once a day, though about three in ten sometimes gave it twice a day. Nearly nine in ten units never measured caffeine levels in the blood. About one in four units began caffeine in the delivery room, soon after birth ^[10].

The picture was different for doxapram. About one unit in four used it as a routine add-on, and countries differed widely; some large countries reported not using it at all ^[10]. It is given through a drip (intravenously), and some units also give it by mouth. Units also differed on what to try when a baby on gentle breathing support, called nasal CPAP (a mask or prongs that give a steady push of air), kept having pauses. Most switched to a different type of non-invasive support (breathing help that does not need a tube in the windpipe), but they chose many different types, and the authors wrote that there is no agreement about the best next step. A quarter of units used a system that automatically adjusts the oxygen a baby receives ^[10].

What families may see on the unit

Parents often notice three things. First, alarms and the team's quick responses, usually a gentle touch to remind the baby to breathe. Second, a daily caffeine dose, which in most European units is first given through a drip ^[10]. Third, a period of extra watching after caffeine is stopped, because around one in ten babies need to restart it ^[1]. If a baby's pauses become more frequent, the team may increase support, change the type of breathing equipment, or discuss adding doxapram, as the surveyed units reported ^[10]. Each of these steps can feel like a setback, but they are normal parts of adjusting care to how each baby is doing, and the team should explain which one they are taking and why.

Why practice varies, and why one dose may not fit all

The survey authors suggest that caffeine practice is similar because it grew out of the CAP trial ^[10]. Doxapram has no such anchor; none of the eight international guidelines compared in the review gave advice on it ^[1]. When there is little firm evidence, hospitals rely on experience, and experiences differ.

The review also explains why babies differ. Tiny babies handle caffeine slowly at first, and the body's ability to clear it improves quickly over the first few weeks, so the same dose can act differently as a baby grows ^[1]. Brain development differs too: two babies of the same age can have brains at different stages of maturity. The authors argue that "a one-size-fits-all approach" misses these differences ^[1]. Differences like these may help explain why some babies need caffeine for longer than others.

What this means for families

If your baby has apnoea of prematurity, it helps to know that pauses are expected, that the team watches closely, and that caffeine is a well-studied treatment with years of evidence behind it. Doxapram is a different story. It has been used for many years and in one look back at 203 babies, most avoided needing a breathing tube ^[11]. A large study following children to age 5 to 6 found no link between doxapram and later developmental problems once the babies were carefully matched ^[12]. A small study of 13 babies, however, found that doxapram changed brain-wave patterns, and its authors urged caution ^[13]. None of this proves harm or benefit, which is why doctors describe it honestly as an add-on that is still being studied.

You can ask your baby's team: what counts as a pause here, and when will you call me? Why is this medicine being used? How will you know it is working? What is the plan for stopping? Asking these questions is part of being your baby's advocate, and good teams welcome them.

What researchers are working on next

A trial called DOXA, which compares doxapram with a placebo, is underway in the Netherlands, Belgium and Canada. It aims to include 396 babies born before 29 weeks, and it will follow them to about 18 to 24 months to see whether doxapram helps or harms their long-term development ^[14].

The review's authors also hope to make treatment more personal. Computers can already spot pauses in breathing from monitor recordings far more completely than hand-written notes, which miss more than eight in ten ^[1]. The authors suggest that these recordings, together with brain-wave tests (EEG), may eventually show which babies need caffeine or doxapram, and how much. They stress that these ideas are early and must be tested in trials before use ^[1]. Other work looks at automatic oxygen control and gentler breathing machines; you can read more in our articles on closed-loop oxygen control, non-invasive NAVA versus nasal CPAP, extended caffeine and what caffeine does and does not do. A crossover study has tested giving extra oxygen only when a pause is detected, which reduced low-oxygen episodes slightly but caused some over-shooting ^[15]. Another study showed that caffeine can still be helpful beyond the usual stopping age in reducing oxygen dips ^[16].

A reassuring takeaway

Apnoea of prematurity generally settles as babies mature, usually by 35 to 40 weeks of postmenstrual age, though sometimes later in the smallest babies ^[10], and caffeine is a long-standing, well-studied support. The two papers show honestly where doctors agree and where they do not, and that researchers are working to give each baby the right amount of help at the right time. For families, the most useful message is that variation between hospitals does not mean any one of them is careless. It may largely reflect questions that science has not yet answered, and that is exactly what current studies are designed to resolve. In the meantime, a team that explains its reasoning, listens to your questions and tells you plainly what is known and unknown is giving you good care.

References

1. Fatunla OAT, Shakir NA, Zandvoort CS, et al. Pharmacological treatment for apnoea of prematurity—the need for an individualised approach. Front Pediatr. 2025;13:1710569. doi:10.3389/fped.2025.1710569 ↩
2. Eichenwald EC; Committee on Fetus and Newborn. Apnea of prematurity. Pediatrics. 2016;137(1):e20153757. doi:10.1542/peds.2015-3757 ↩
3. Schmidt B, Roberts RS, Davis P, et al. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006;354(20):2112-2121. doi:10.1056/NEJMoa054065 ↩
4. 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):1893-1902. doi:10.1056/NEJMoa073679 ↩
5. 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: an 11-year follow-up of the CAP randomized clinical trial. JAMA Pediatr. 2017;171(6):564-572. doi:10.1001/jamapediatrics.2017.0238 ↩
6. Carlo WA, Eichenwald EC, Carper BA, et al. Extended caffeine for apnea in moderately preterm infants: the MoCHA randomized clinical trial. JAMA. 2025;333(24):2154-2163. doi:10.1001/jama.2025.5791 ↩
7. Urru SA, Geist M, Carlinger R, et al. Strategies for cessation of caffeine administration in preterm infants. Cochrane Database Syst Rev. 2024;7(7):CD015802. doi:10.1002/14651858.CD015802.pub2 ↩
8. Vliegenthart RJS, ten Hove CH, Onland W, van Kaam AHLC. Doxapram treatment for apnea of prematurity: a systematic review. Neonatology. 2017;111(2):162-171. doi:10.1159/000448941 ↩
9. Evans S, Avdic E, Pessano S, et al. Doxapram for the prevention and treatment of apnea in preterm infants. Cochrane Database Syst Rev. 2023;10(10):CD014145. doi:10.1002/14651858.CD014145.pub2 ↩
10. Lavizzari A, Hutten GJ, Heiring C, et al. Management of apnoea in extremely preterm infants: a European survey. Neonatology. 2025;122(6):677-684. doi:10.1159/000547546 ↩
11. Flint R, Halbmeijer N, Meesters N, et al. Retrospective study shows that doxapram therapy avoided the need for endotracheal intubation in most premature neonates. Acta Paediatr. 2017;106(5):733-739. doi:10.1111/apa.13761 ↩
12. Tréluyer L, Zana-Taieb E, Jarreau PH, et al. Doxapram for apnoea of prematurity and neurodevelopmental outcomes at age 5-6 years. Arch Dis Child Fetal Neonatal Ed. 2024;109(4):443-449. doi:10.1136/archdischild-2023-326170 ↩
13. Czaba-Hnizdo C, Olischar M, Rona Z, et al. Amplitude-integrated electroencephalography shows that doxapram influences the brain activity of preterm infants. Acta Paediatr. 2014;103(9):922-927. doi:10.1111/apa.12681 ↩
14. Poppe JA, Flint RB, Smits A, et al. Doxapram versus placebo in preterm newborns: a study protocol for an international double blinded multicentre randomized controlled trial (DOXA-trial). Trials. 2023;24(1):656. doi:10.1186/s13063-023-07683-5 ↩
15. Marshall A, Ladlow OJ, Bannink C, et al. Apnoea-triggered increase in fraction of inspired oxygen in preterm infants: a randomised cross-over study. Arch Dis Child Fetal Neonatal Ed. 2024;109(1):81-86. doi:10.1136/archdischild-2023-325849 ↩
16. Rhein LM, Dobson NR, Darnall RA, et al. Effects of caffeine on intermittent hypoxia in infants born prematurely: a randomized clinical trial. JAMA Pediatr. 2014;168(3):250-257. doi:10.1001/jamapediatrics.2013.4371 ↩