Two Gentle Ways to Help a Premature Baby Breathe — and What a New Study Says About Them

A plain-language look at Gover and colleagues' 2025 trial comparing high-flow nasal cannula with RAM-cannula pressure support

When a premature baby needs help breathing but is not sick enough to need a tube down the windpipe, doctors reach for soft prongs that sit in the baby's nose. A 2025 study compared the two gentlest of these methods head-to-head for the first time and found they worked about equally well, with one — high-flow warm air — causing no nose injuries at all. For most premature babies born after 28 weeks, this means parents and clinicians can choose the method that is most comfortable for their baby without giving up on how well it works.

Why This Question Matters

Premature babies often have lungs that are not quite ready. Instead of putting a breathing tube into the windpipe (which can injure delicate lungs), neonatal teams try to support breathing from the outside, through the nose. For many years the standard way to do this used firm prongs that fit tightly in the nostrils to seal in the air pressure [1]. Those firm prongs work, but the tight fit has a downside every NICU nurse knows well: it can rub, redden, and sometimes break down the skin of a tiny baby's nose, and babies often squirm against them. So over the last decade, two "kinder" methods became popular because they are more comfortable — but they became popular before anyone had directly tested them against each other. This new study set out to fix that.

The two methods sound technical, but the idea behind each is simple. The first, high-flow nasal cannula (the study calls it HHHFNC), blows a steady stream of warm, moist air through soft prongs. The gentle rush of air helps flush out stale air and makes breathing easier, and because the prongs don't seal the nose shut, they rarely cause injury [2]. The second, called CLNT-NIPPV (delivered through a soft "RAM" cannula), gives the baby small, timed puffs of extra pressure through similar soft prongs — a bit more like gentle assisted breaths. An earlier study had shown this softer cannula was as good as the old firm prongs while being kinder to the nose [3]. Both methods are widely trusted, but until now no one knew whether one was better than the other.

What the Researchers Did

The team, working in three hospitals in Israel, enrolled 130 premature babies and used the equivalent of a coin flip to assign each baby to one method or the other — 65 babies to each group [4]. Randomly assigning babies this way is the fairest possible test, because it means the two groups start out very similar and any difference at the end is likely due to the method itself, not to which babies happened to be sicker. Most of the babies (about 8 in 10) were born after 28 weeks of pregnancy, and most started on their assigned method right after birth. The very smallest, most premature babies were included only after they had already been on a breathing tube and were ready to come off it.

The main thing the researchers measured was whether the assigned method "failed" within the first week — meaning the baby needed much more oxygen, built up too much carbon dioxide, had too many pauses in breathing, or needed a breathing tube after all. Importantly, if a baby simply needed a dose of surfactant (a medicine that helps stiff lungs open up), that did not count as a failure, because giving surfactant is a normal, expected part of care with either method.

What They Found

The two methods came out very close. Breathing support "failed" in about 12 out of 100 babies on high-flow, compared with about 23 out of 100 on the RAM-cannula method [4]. By the study's careful statistical rules, that was close enough to say high-flow was "not worse" — which was exactly what the researchers set out to test. It's worth being honest about what this does and doesn't mean: the numbers leaned in high-flow's favor, but the study was not large enough to claim high-flow is actually better. Think of it as a tie in which one runner happened to be a step ahead at the finish line, but not by enough to be sure it wasn't chance. Reassuringly, when a few babies on high-flow did struggle, most were simply switched to the other method and did fine without a breathing tube — the two methods back each other up.

It also helps to know what "failing" actually looked like for the small number of babies it happened to, because it shows how carefully the team was watching. A baby was counted as needing a change of plan if it began needing a lot more oxygen, if its blood tests showed too much carbon dioxide building up, if it had too many pauses in its breathing, or if it needed a breathing tube after all. These are exactly the signs the bedside nurses and doctors monitor around the clock, and in most cases a struggling baby could be moved to the other gentle method rather than straight to a breathing tube. In other words, "failure" in this study did not mean something went suddenly wrong — it meant the team noticed early that a baby needed a bit more help and adjusted, which is precisely how good NICU care is supposed to work.

The clearest difference was about comfort and the nose. None of the babies on high-flow had any nose injury, compared with about 1 in 9 babies on the RAM cannula [5]. That fits with years of experience showing high-flow is easy on a baby's skin. The trade-off was that babies tended to stay on high-flow a bit longer before coming off — though the total number of days needing any breathing help, and the total time on extra oxygen, were the same. Rates of the serious complications of prematurity, and how long babies stayed in the hospital, did not differ between the groups.

What This Means for Families

If your baby is premature and needs breathing help through the nose, the encouraging bottom line is that both of these gentle methods work well, and neither requires a breathing tube. For most babies — especially those born after 28 weeks — the choice can come down to what is most comfortable and what your NICU team knows best. If a baby's nose is getting sore, high-flow is especially kind to the skin [6]. If a baby needs a little extra push of pressure, the RAM-cannula method offers that. Neither choice affects feeding or how soon a baby goes home in a way that families would notice, which matches earlier research finding no feeding downside to high-flow [7]. These are the kinds of small, practical decisions your care team makes every day, and this study gives them good reason to prioritize your baby's comfort.

One honest caution: the study included only a small number of the tiniest, most premature babies (born at or before 28 weeks), and it could not give a clear answer for them [8]. For those babies, whose lungs are the most fragile, doctors will still lean on the sturdier, pressure-based methods they trust most [9]. That is not a mark against high-flow — it simply means the question hasn't been fully answered for the smallest babies yet, and good doctors don't guess where the evidence runs out.

A Note on How We Got Here

It is easy to forget how far this care has come. A generation ago, a premature baby who couldn't breathe well would almost certainly have been placed on a ventilator through a breathing tube — lifesaving, but hard on immature lungs. The move toward supporting breathing gently through the nose, and then toward interfaces designed specifically for comfort, represents decades of careful research trying to help babies breathe with the least possible harm [10]. This new trial is one more step in that long effort: not a dramatic breakthrough, but a careful confirmation that lets clinicians choose comfort without sacrificing safety.

What Researchers Are Working On Next

The main open question is about those smallest, earliest babies. Researchers now want to run a larger study focused specifically on infants born at 28 weeks or earlier, to learn whether high-flow is a safe choice for them too, and to agree on the best way to gradually wean babies off high-flow so they aren't left on it longer than needed. Until then, this study offers families a genuinely reassuring message: for the great majority of premature babies who need a little help breathing, kindness and effectiveness do not have to be a trade-off.

References

  1. Sweet DG, Carnielli VP, Greisen G, et al. European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update. Neonatology. 2023;120(1):3–23. doi:10.1159/000528914 ↩
  2. Yoder BA, Stoddard RA, Li M, et al. Heated, Humidified High-Flow Nasal Cannula Versus Nasal CPAP for Respiratory Support in Neonates. Pediatrics. 2013;131(5):e1482–e1490. doi:10.1542/peds.2012-2742 ↩
  3. Hochwald O, Riskin A, Borenstein-Levin L, et al. Cannula With Long and Narrow Tubing vs Short Binasal Prongs for Noninvasive Ventilation in Preterm Infants: Noninferiority Randomized Clinical Trial. JAMA Pediatr. 2021;175(1):36–43. doi:10.1001/jamapediatrics.2020.3579 ↩
  4. Gover A, Smolkin T, Molad M, et al. HHHFNC Versus NIPPV Delivered by Long Narrow Cannula in Preterm Infants: Randomized Noninferiority Trial. Pediatr Pulmonol. 2025;60(6):e71167. doi:10.1002/ppul.71167 ↩
  5. Klingenberg C, Pettersen M, Hansen EA, et al. Patient Comfort During Treatment With Heated Humidified High Flow Nasal Cannulae Versus Nasal CPAP: A Randomised Cross-Over Trial. Arch Dis Child Fetal Neonatal Ed. 2014;99(2):F134–F137. doi:10.1136/archdischild-2013-304525 ↩
  6. Manley BJ, Owen LS, Doyle LW, et al. High-Flow Nasal Cannulae in Very Preterm Infants After Extubation. N Engl J Med. 2013;369(15):1425–1433. doi:10.1056/NEJMoa1300071 ↩
  7. Cresi F, Maggiora E, Lista G, et al. Effect of Nasal CPAP vs HHHFNC on Feeding Intolerance in Preterm Infants With RDS: The ENTARES Randomized Clinical Trial. JAMA Netw Open. 2023;6(7):e2323052. doi:10.1001/jamanetworkopen.2023.23052 ↩
  8. Roberts CT, Owen LS, Manley BJ, et al. Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants. N Engl J Med. 2016;375(12):1142–1151. doi:10.1056/NEJMoa1603694 ↩
  9. Hodgson KA, Wilkinson D, De Paoli AG, Manley BJ. Nasal High Flow Therapy for Primary Respiratory Support in Preterm Infants. Cochrane Database Syst Rev. 2023;5:CD006405. doi:10.1002/14651858.CD006405.pub4 ↩
  10. Lavizzari A, Colnaghi M, Ciuffini F, et al. Heated, Humidified High-Flow Nasal Cannula vs Nasal CPAP for RDS of Prematurity: A Randomized Clinical Noninferiority Trial. JAMA Pediatr. 2016. doi:10.1001/jamapediatrics.2016.1243 ↩