Letting Carbon Dioxide Run a Little Higher to Get Fragile Babies Off the Breathing Machine Sooner

A plain-language look at a 2025 study testing a gentler ventilation strategy for very premature babies still on a breathing machine at two weeks of age

A 2025 study of 130 very premature babies who were still on a breathing machine at about two weeks of age found that allowing their blood carbon dioxide to sit a little higher than usual — while carefully keeping their blood chemistry within safe limits — helped them come off the machine sooner, gaining on average about five extra days free of the ventilator over four weeks, with no increase in harm [1]. The approach did not clearly reduce chronic lung disease, but it appeared safe and pointed toward gentler care.

Why This Question Matters

When a baby is born many weeks early, the lungs are among the last organs to be ready for the outside world. Many of the tiniest babies need a breathing machine, called a ventilator, to survive their first days and sometimes weeks. The ventilator is lifesaving, but it is also a blunt instrument: pushing air into delicate, underdeveloped lungs can itself cause injury over time [2]. That injury contributes to a chronic lung condition of prematurity called bronchopulmonary dysplasia, or BPD — one of the most common lasting complications for babies born very early [1]. Despite many advances in newborn care, the number of babies who develop BPD has barely changed in over twenty years [3], and its effects can follow children into their school years and beyond, with some carrying reduced lung capacity into adulthood [4]. So one of the central goals of modern newborn intensive care is simple to state and hard to achieve: get babies off the breathing machine as quickly and safely as possible.

The History Behind "Gentle Ventilation"

For decades, doctors caring for premature babies have wrestled with how forcefully to support breathing. Every breath the machine delivers helps clear carbon dioxide — the waste gas our lungs breathe out — but delivering those breaths with too much pressure or volume can scar the lungs [5]. Out of this tension came an idea called "permissive hypercapnia," a technical name for a gentle principle: instead of working the machine hard to keep carbon dioxide at a normal level, doctors deliberately allow the carbon dioxide to run somewhat higher, which lets them dial the machine down and spare the lungs [6]. Early studies in the 1990s and 2000s were encouraging. A small trial found that tolerating higher carbon dioxide in the first few days helped babies come off the ventilator [7], and a "minimal ventilation" approach in the first week and a half reduced the number of the smallest babies still needing a machine later on [8].

But medicine advances by testing its own hopeful ideas, and the larger studies that followed were more sobering. A big multi-hospital European trial known as PHELBI, which allowed higher carbon dioxide across the first two weeks, found no real benefit for lung disease and hinted at a possible increase in a serious gut complication [9]. That left doctors in an uncomfortable spot. The gentle idea seemed to help in the very first days but not clearly over the first two weeks — and almost no one had studied what happens after two weeks, when a subset of the most fragile babies are still stuck on the ventilator with ongoing lung disease. Families of these babies, and the teams caring for them, were essentially working without a map for that stretch of the journey. A small pilot study by the research team behind the new trial suggested the question was worth answering properly [10].

What the Researchers Did

The new study, led by Dr. Colm Travers and colleagues at a large neonatal intensive care unit in Alabama, set out to fill that gap [1]. They enrolled 130 premature babies who were still on a breathing machine somewhere between one and two weeks after birth. These were among the most vulnerable babies in the unit — on average born at around 24 to 25 weeks of pregnancy (a full-term pregnancy is 40 weeks) and weighing only about 660 grams, roughly a pound and a half.

Each baby was randomly assigned — like a flip of a coin — to one of two care plans for the next four weeks. In one group, the team allowed a higher carbon dioxide level (a target range doctors describe as 60 to 75 on their scale). In the other, they kept carbon dioxide at a lower, more traditional level (40 to 55). Randomly assigning babies is the fairest way to compare two approaches, because it means any difference in how the groups do is most likely due to the treatment rather than to the babies being different to begin with. Importantly, in both groups the team set a firm safety limit on the blood's acidity (its pH): they only allowed carbon dioxide to rise as long as the blood chemistry stayed within a safe window. To track carbon dioxide without constant blood draws, they used a gentle skin sensor. Babies who improved were moved to softer, non-invasive breathing support rather than the full ventilator [11], and their oxygen levels were watched using well-established safety targets [12].

What They Found

The main result was clear and encouraging. Babies in the higher-carbon-dioxide group spent more time alive and off the breathing machine — an average of 11 days free of the ventilator over the four-week period, compared with 6 days in the lower group [1]. In practical terms, allowing carbon dioxide to run a little higher bought these babies about five extra days of freedom from invasive breathing support, and they spent that time on gentler, non-invasive support instead. Just as importantly, this did not come at the cost of survival: the two groups were essentially identical in how many babies were alive, and there was no increase in complications such as gut problems, brain bleeds, or breathing setbacks.

The study also looked at whether the gentler approach reduced chronic lung disease (BPD) or death, using a standard modern definition of the condition [13]. Here the picture was hopeful but not conclusive. Fewer babies in the higher-carbon-dioxide group had serious BPD or died — 44 percent versus 59 percent — but this difference was not large enough to rule out chance, because the study was designed mainly to measure ventilator time, not lung disease. When children were checked again at about two years of age, development was similar in both groups, which is reassuring: getting babies off the ventilator sooner did not appear to trade short-term gains for later harm.

What This Means for Families

If your baby is very premature and still needs a breathing machine after the first week or two, this study offers cautious good news. It suggests that a widely used, gentle strategy — tolerating a somewhat higher carbon dioxide level within careful safety limits — can help babies move off the ventilator sooner and onto softer support, without adding risk. This is not a new drug or a dramatic intervention; it is a thoughtful adjustment to how the breathing machine is managed, aimed at protecting fragile lungs. Parents should know that when a care team allows carbon dioxide to run a little high, this is usually a deliberate, monitored choice rather than a problem — a way of being gentler with the lungs while keeping the baby safe.

It also helps to understand why this particular group of babies was studied. The babies in this trial were not all premature infants, but specifically those who were still on a breathing machine one to two weeks after birth — a smaller, more fragile group who tend to have the hardest time with their lungs. Earlier research had shown that tolerating higher carbon dioxide in the very first days could help, but a large European study found it made little difference across the first two weeks [9]. What made this new study valuable is that it looked at a later, largely unexamined window — the weeks after the first two — when families are often anxiously waiting for their baby to turn a corner. Answering that specific question gives care teams better footing during a stretch of the NICU journey that previously had very little evidence to guide it.

It is also worth understanding the study's limits, because honest science acknowledges them. This was a single hospital's experience with 130 babies, and the team knew which plan each baby was on, which can subtly influence care. The two groups also ended up with carbon dioxide levels closer together than the researchers intended, which usually makes it harder to detect a difference — so the real benefit of the gentler approach may be even larger than what the study measured. The clearest finding is that the approach reduces time on the ventilator; whether it truly prevents chronic lung disease is a question that still needs larger studies to answer. None of this should worry a family whose team is using this approach — it simply reflects how carefully researchers weigh what they can and cannot yet claim.

What Comes Next

Researchers are now calling for bigger trials across multiple hospitals to confirm whether this gentler strategy not only shortens ventilator time but also lowers the chances of lasting lung disease [1]. They also want to pin down the safest carbon dioxide and blood-chemistry targets and to follow children for longer to be sure the approach helps their lungs and development in the years ahead. For now, this study adds a useful piece to a long-running effort to make breathing support for the tiniest babies as gentle, and as brief, as it can safely be.

References

  1. Travers CP, Gentle SJ, Shukla VV, et al. Late Permissive Hypercapnia for Mechanically Ventilated Preterm Infants: A Randomized Trial. Pediatric Pulmonology. 2025;60(6):e71165. doi:10.1002/ppul.71165 ↩
  2. McEvoy CT, Jain L, Schmidt B, Abman S, Bancalari E, Aschner JL. Bronchopulmonary Dysplasia: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases. Annals of the American Thoracic Society. 2014;11(Suppl 3):S146–S153. doi:10.1513/AnnalsATS.201312-424LD ↩
  3. Horbar JD, Greenberg LT, Buzas JS, Ehret DEY, Soll RF, Edwards EM. Trends in Mortality and Morbidities for Infants Born 24 to 28 Weeks in the US: 1997–2021. Pediatrics. 2024;153(1):e2023064153. doi:10.1542/peds.2023-064153 ↩
  4. Doyle LW, Carse E, Adams AM, Ranganathan S, Opie G, Cheong JLY. Ventilation in Extremely Preterm Infants and Respiratory Function at 8 Years. New England Journal of Medicine. 2017;377(4):329–337. doi:10.1056/NEJMoa1700827 ↩
  5. Walsh MC, Morris BH, Wrage LA, et al. Extremely Low Birthweight Neonates With Protracted Ventilation: Mortality and 18-Month Neurodevelopmental Outcomes. Journal of Pediatrics. 2005;146(6):798–804. doi:10.1016/j.jpeds.2005.01.047 ↩
  6. Thome UH, Ambalavanan N. Permissive Hypercapnia to Decrease Lung Injury in Ventilated Preterm Neonates. Seminars in Fetal and Neonatal Medicine. 2009;14(1):21–27. doi:10.1016/j.siny.2008.08.005 ↩
  7. Mariani G, Cifuentes J, Carlo WA. Randomized Trial of Permissive Hypercapnia in Preterm Infants. Pediatrics. 1999;104(5 Pt 1):1082–1088. doi:10.1542/peds.104.5.1082 ↩
  8. Carlo WA, Stark AR, Wright LL, et al. Minimal Ventilation to Prevent Bronchopulmonary Dysplasia in Extremely-Low-Birth-Weight Infants. Journal of Pediatrics. 2002;141(3):370–375. doi:10.1067/mpd.2002.127507 ↩
  9. Thome UH, Genzel-Boroviczeny O, Bohnhorst B, et al. Permissive Hypercapnia in Extremely Low Birthweight Infants (PHELBI): A Randomised Controlled Multicentre Trial. Lancet Respiratory Medicine. 2015;3(7):534–543. doi:10.1016/S2213-2600(15)00204-000204-0) ↩
  10. Travers CP, Carlo WA, Nakhmani A, et al. Late Permissive Hypercapnia and Respiratory Stability Among Very Preterm Infants: A Pilot Randomised Trial. Archives of Disease in Childhood - Fetal and Neonatal Edition. 2023;108(5):530–534. doi:10.1136/archdischild-2022-325166 ↩
  11. Lemyre B, Deguise MO, Benson P, Kirpalani H, De Paoli AG, Davis PG. Nasal Intermittent Positive Pressure Ventilation (NIPPV) Versus Nasal Continuous Positive Airway Pressure (NCPAP) for Preterm Neonates After Extubation. Cochrane Database of Systematic Reviews. 2023;7(7):CD003212. doi:10.1002/14651858.CD003212.pub4 ↩
  12. Askie LM, Darlow BA, Finer N, et al. Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-Analysis Collaboration. JAMA. 2018;319(21):2190–2201. doi:10.1001/jama.2018.5725 ↩
  13. Jensen EA, Dysart K, Gantz MG, et al. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-Based Approach. American Journal of Respiratory and Critical Care Medicine. 2019;200(6):751–759. doi:10.1164/rccm.201812-2348OC ↩