A Longer First Breath for Struggling Preemies? What a New Trial Found

Understanding a new Iranian study of "sustained lung inflation" in premature babies who develop breathing trouble minutes after birth

When a premature baby who seemed to be breathing reasonably well at birth suddenly starts struggling a few minutes later, the neonatal team has to decide quickly how to help. Doctors have several tools for supporting a newborn's lungs, but deciding which one to add, and exactly when, is not always straightforward, and the research evidence behind these decisions has itself shifted considerably over the years.

A new study from two university teaching hospitals in Isfahan, Iran, tested one of those options directly in this situation: giving one extra, longer breath through soft nasal prongs, on top of the usual breathing-support machine, to see whether it eased a premature baby's early breathing struggle. The result was more mixed, and more puzzling, than the researchers had hoped for [1].

Why This Question Matters, and How We Got Here

Many babies born before about 34 weeks of pregnancy have lungs that are not quite ready to fill with air and stay open on their own, a condition doctors call respiratory distress syndrome. For decades, the mainstay of help has been continuous positive airway pressure, usually shortened to CPAP: a gentle, steady stream of air or oxygen delivered through small prongs in the baby's nose, which keeps the tiny air sacs in the lungs from collapsing between breaths. CPAP alone is often enough. But some babies need more, and researchers have spent years trying to figure out the best way to give that "more" without causing harm.

One idea, tried at various points over the past fifteen years, is called sustained lung inflation: instead of the usual rapid little breaths a resuscitation device delivers, the team holds a single longer breath — around 10 to 15 seconds — hoping to more efficiently push out the fluid that fills a baby's lungs before birth and open the air sacs in one steady step, rather than gradually. Early small studies, including trials led by researchers named Lista and Jiravisitkul, tried this right at delivery, in babies who needed help breathing from the very first minute, and reported that it seemed to reduce how often those babies later needed a breathing machine; a further study by a team led by Abd El-Fattah looked at exactly how strong and how long that breath should be [2][3][4]. Based on results like these, some hospitals began trying the technique in their delivery rooms.

That changed with a much larger study, the Sustained Aeration of Infant Lungs trial — known by its short name, SAIL — which tested the same idea across 18 newborn intensive care units in nine countries [5]. Partway through, the independent safety committee overseeing SAIL stopped the trial early: babies who received the longer breath were dying in the first two days of life more often than babies who received standard help — about 7 in 100, compared with about 1 in 100 — with no offsetting benefit in the long run. Several careful reviews that combined the results of many smaller studies together, including one from the respected Cochrane research group, later confirmed that this technique, used right at delivery, could not be recommended as routine care [6][7][8]. Today's international guidelines for newborn breathing support reflect that caution, favouring gentle CPAP as the starting point for premature babies who are breathing on their own [9][10].

That should sound like the end of the story — but the new Iranian trial asks a different, narrower question that many NICU parents will recognise from their own baby's early days: what about a baby who breathes fine at delivery, is settled onto CPAP, and only then, a few minutes later, starts to show signs of trouble?

What the Researchers Did

The research team, based at two university teaching hospitals in Isfahan, Iran, studied 74 premature babies born between about 28 and 34 weeks of pregnancy, all weighing more than 1,000 grams (about 2.2 pounds), who were breathing adequately at birth but then developed signs of respiratory distress — fast, laboured breathing; grunting; needing more oxygen — within 5 to 10 minutes. Half of the babies, chosen at random, received a single 10-second sustained breath through nasal prongs before being placed on CPAP; the other half went straight onto CPAP alone. The two groups of babies were very similar in how premature they were, how much they weighed, and other starting factors, so any differences seen afterward could be attributed to the treatment rather than to chance differences between the groups [1].

What They Found

The results were genuinely a mixed picture. Babies who got the extra sustained breath did not need a breathing machine (mechanical ventilator) any more or less often than babies on CPAP alone. But they needed a rescue medicine called surfactant — which coats the inside of the air sacs and helps them stay open — much less often: about 19 in 100 babies in the sustained-inflation group needed it, compared with about 54 in 100 babies in the CPAP-alone group. Babies who received the sustained breath also went home from the hospital sooner on average, by about eight days (roughly 37 days in hospital versus roughly 45 days) [1].

But there was a puzzle: babies who got the sustained breath needed to stay on the CPAP machine itself for almost twice as long afterward — about 82 hours on average, compared with about 40 hours for babies who went straight onto CPAP. The researchers had expected the opposite and could not fully explain why this happened. Reassuringly, no baby in either group died during the study, and serious problems sometimes seen in premature babies — bleeding in the brain, a bowel condition called necrotising enterocolitis, and small air leaks around the lung — were rare and occurred at similar, low rates in both groups.

For parents watching this happen at the bedside, it can help to know what these terms actually mean in practice. CPAP looks like a small mask or a pair of soft prongs resting just inside your baby's nostrils, connected by tubing to a machine that delivers a steady, gentle flow of air or oxygen — it does not breathe for your baby, but it holds the tiny air sacs in their lungs slightly open between breaths, the way a tent pole holds up canvas. A "sustained inflation" is not a separate ongoing treatment but a single, brief action — about 10 seconds, roughly the time it takes to read this sentence aloud twice — given once, at one particular moment, before your baby is settled onto CPAP as usual. Nothing about either approach is invasive or requires a breathing tube; a baby needing more support than either of these provides would instead be moved onto a mechanical ventilator, a separate and more involved form of help that neither group in this study needed more or less often than the other.

What This Means for Families

If your baby is cared for in a NICU that uses CPAP for early breathing trouble, this study on its own is not a reason to expect — or to ask for — a change in how your baby is treated. It is one small trial, conducted in two hospitals in one country, and its most striking benefit (less need for surfactant) came alongside a finding the researchers themselves could not explain (more time on CPAP). Good neonatal teams weigh findings like these carefully, waiting for larger, more diverse studies to confirm or clarify a result before changing how they care for babies day to day. What this study does offer families is a window into how genuinely careful — and sometimes genuinely uncertain — the process of improving newborn care actually is: even a technique with a plausible-sounding rationale and encouraging early results (as sustained inflation had, a decade ago) can turn out, on closer and larger study, to need real caution, as the SAIL trial showed, and even a promising smaller result, like this one, can raise as many questions as it answers.

What Researchers Are Working on Next

The authors of this study, and the wider community of neonatal researchers, agree that larger trials — across multiple hospitals, with clearly agreed rules for exactly when to give a rescue medicine like surfactant, and with follow-up that continues well beyond the hospital stay to check on babies' lung and developmental health months and years later — are needed before this approach could be considered for wider use. Families whose babies took part in a study like this one — and families who are asked, in future, to consider enrolling their own baby in a similar trial — are contributing to exactly that kind of careful, incremental progress, even when a single study's answer turns out to be more of a lead than a conclusion. That is, in a real sense, how essentially all of today's standard NICU care came to be: not from one decisive study, but from a long chain of trials, some encouraging and some sobering, each narrowing the uncertainty a little further. For readers curious about how researchers are separately rethinking the very first breaths a baby takes at birth, including how the timing of clamping the umbilical cord interacts with breathing support, our related article on that topic offers useful further context ([In[Neo]Sight: Ventilating Before the Cord Is Cut](https://inneosight.org/en-US/articles/vent-first-intact-cord-ventilation)).

References

  1. Mohammadizadeh M, Moeini M, Barekatain B. Sustained Lung Inflation in Preterm Infants with Signs of Respiratory Distress: A Randomized Controlled Trial. Advanced Biomedical Research. 2026;15:10. doi:10.4103/abr.abr_526_23 ↩
  2. Lista G, Boni L, Scopesi F, et al. Sustained lung inflation at birth for preterm infants: A randomized clinical trial. Pediatrics. 2015;135(2):e457–e464. doi:10.1542/peds.2014-1692 ↩
  3. Jiravisitkul P, Rattanasiri S, Nuntnarumit P. Randomized controlled trial of sustained lung inflation for resuscitation of preterm infants in the delivery room. Resuscitation. 2017;111:68–73. doi:10.1016/j.resuscitation.2016.12.003 ↩
  4. Abd El-Fattah N, Nasef N, Al-Harrass MF, Khashaba M. Sustained lung inflation at birth for preterm infants at risk of respiratory distress syndrome: The proper pressure and duration. Journal of Neonatal-Perinatal Medicine. 2017;10(4):409–417. doi:10.3233/NPM-171760 ↩
  5. Kirpalani H, Ratcliffe SJ, Keszler M, et al. Effect of sustained inflations vs intermittent positive pressure ventilation on bronchopulmonary dysplasia or death among extremely preterm infants: The SAIL randomized clinical trial. JAMA. 2019;321(12):1165–1175. doi:10.1001/jama.2019.1660 ↩
  6. Foglia EE, te Pas AB, Kirpalani H, et al. Sustained inflation vs standard resuscitation for preterm infants: A systematic review and meta-analysis. JAMA Pediatrics. 2020;174(4):e195897. doi:10.1001/jamapediatrics.2019.5897 ↩
  7. Bruschettini M, O'Donnell CP, Davis PG, Morley CJ, Moja L, Calevo MG. Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes. Cochrane Database of Systematic Reviews. 2020;3:CD004953. doi:10.1002/14651858.CD004953.pub4 ↩
  8. Kapadia VS, Urlesberger B, Soraisham A, et al. Sustained lung inflations during neonatal resuscitation at birth: A meta-analysis. Pediatrics. 2021;147(1):e2020021204. doi:10.1542/peds.2020-021204 ↩
  9. Wyckoff MH, Wyllie J, Aziz K, et al. Neonatal Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Circulation. 2020;142(16_suppl_1):S185–S221. doi:10.1161/CIR.0000000000000895 ↩
  10. Madar J, Roehr CC, Ainsworth S, et al. European Resuscitation Council Guidelines 2021: Newborn resuscitation and support of transition of infants at birth. Resuscitation. 2021;161:291–326. doi:10.1016/j.resuscitation.2021.02.014 ↩