A Gentler Way to Give a Life-Saving Lung Medicine — and What It Means Two Years Later

A large Italian study followed extremely premature babies to age two to see whether opening the lungs before giving surfactant changes how children grow and develop

When a baby is born extremely early, doctors often give a medicine called surfactant that keeps the tiny air sacs in the lungs from collapsing, and researchers have been looking for the gentlest way to deliver it. A large Italian study tested adding a brief lung-opening step just before the surfactant, then checked back when the children were two years old. The encouraging news for families is that this extra step appears safe over the long run: children in both groups grew, developed, and breathed about the same by age two.

Why This Question Matters

Babies born extremely early — here, between 24 and nearly 28 weeks of pregnancy, when a typical pregnancy lasts about 40 weeks — have lungs that are not yet ready to breathe air. Their lungs lack enough surfactant, a natural soap-like substance that coats the inside of the millions of tiny air sacs and stops them from sticking shut with every breath. Without it, breathing is like trying to inflate a balloon that keeps collapsing. For decades, the treatment has been to give extra surfactant as a medicine, and modern guidelines make surfactant plus gentle breathing support the foundation of care for these fragile newborns [1].

But there has always been a catch. To give surfactant the traditional way, doctors place a small breathing tube, deliver the medicine, and then remove the tube so the baby can go back to breathing with gentle pressure through the nose — an approach doctors call "intubate–surfactant–extubate," or IN-SUR-E. This method was a genuine advance because it shortened the time babies spent on a breathing machine [2], and later research even showed many babies can start with nose support alone [3]. Doctors have kept looking for ever-gentler methods, including giving surfactant through a very thin tube without a full breathing tube at all [4], [5]. The problem the newest idea tries to solve is simple to picture: if the lungs are still partly collapsed when the surfactant goes in, the medicine spreads unevenly and does not work as well, and the baby often ends up back on the machine.

The New Idea, and How It Was Tested

The strategy in this study, called "intubate–recruit–surfactant–extubate" (IN-REC-SUR-E), adds one step. After the breathing tube is placed, doctors use a special gentle ventilator to briefly and evenly open up the lungs — a step called lung recruitment — before giving the surfactant, and then remove the tube. The thinking is that a fully open lung soaks up and holds the medicine better, like watering a garden after loosening the soil rather than before.

An earlier report from this same research team had already shown a real short-term win: babies who got the lung-opening step needed a breathing machine only about half as often in the first three days of life. That first study was large and careful — it involved 218 extremely premature babies across 35 hospitals in Italy [6]. But parents and doctors care about much more than the first three days. What they really want to know is whether a treatment given in the first hours of life makes any difference to how a child is doing years later. That is the question this new follow-up study set out to answer [7].

The researchers invited back the children who had survived and were able to examine 137 of them at age two (adjusted for how early they were born). Doctors who did not know which treatment each child had received measured how the children were developing — including movement, thinking, vision, and hearing — as well as their height, weight, and head size, and whether they had frequent chest infections [7]. Having the examiners "blinded" in this way is important, because it means their judgments could not be swayed by knowing which group a child was in.

What They Found

The main result was reassuring. When the researchers combined death after going home and serious disability into one measure, the numbers were 20 out of every 100 children in the traditional group and about 14 out of every 100 in the lung-opening group — a difference small enough that it could easily be due to chance [7]. In plain terms, the two approaches came out about even. Every individual measure of development — serious disability, cerebral palsy (a condition affecting movement), and thinking difficulties — leaned slightly in favor of the lung-opening group, but none of these differences was large enough for the researchers to be confident it was real rather than luck. Children in both groups were similar in height, weight, and head size at age two, and they had similar rates of coughs, colds, and hospital stays for breathing problems.

One earlier benefit did hold up: in this same group of children, the babies who got the lung-opening step had again needed the breathing machine far less in their first three days — about 23 out of 100, compared with about 48 out of 100 with the traditional method [7]. So the short-term advantage was real and repeatable; it simply did not translate into a measurable head start or setback by age two.

What This Means for Families

If your baby is born very early and needs surfactant, the honest and comforting takeaway is that the exact technique the team uses to deliver it — whether or not they add a lung-opening step — is not known to change your child's chances of walking, talking, growing, or breathing well at age two. That lets the medical team choose the method that fits your baby's immediate needs and their hospital's equipment and training, without fear that they are trading a short-term gain for a long-term cost. The lung-opening step has a clear short-term benefit (less time on a breathing machine), and now we know it does not appear to cause harm down the road.

It also helps to know what does shape a child's long-term outcome. In this study, the strongest factors were not the surfactant technique but things like birth weight and whether the baby had bleeding in the brain early on. Chronic lung disease of prematurity, known as bronchopulmonary dysplasia, also remains one of the biggest influences on how these children fare [8], [9]. This is why NICU teams work so hard on the whole picture of care, not any single step.

An Honest Look at the Limits

No single study settles a question completely, and the researchers were candid about this one's limits. Because more of the sickest babies survived in the lung-opening group, the two groups of two-year-olds were not perfectly matched — the lung-opening group carried forward more fragile survivors, which actually makes its slightly better development scores a little more encouraging than they first appear. The study was also not large enough to detect small differences with certainty, so it can neither promise a benefit nor completely rule out a rare harm on any one measure. Some of the growth and breathing information was collected through a questionnaire during the COVID-19 pandemic, which disrupted the usual in-person testing. These are reasons to see the results as reassuring rather than final. Reassuringly, other research on this type of gentle ventilator has generally not found lasting harm to development [10], and the study used a standard, widely accepted way of diagnosing cerebral palsy so its results can be compared with other work [11].

What Researchers Are Working On Next

The next big question doctors want answered is how the lung-opening method compares not with the older technique but with the newest, thinnest-tube methods that avoid a full breathing tube altogether [4]. A future study designed specifically to compare these approaches, and large enough to measure development reliably, would help families and doctors choose with even more confidence. Researchers also hope to follow children like these for longer than two years — into the school-age years, when subtle differences in learning, attention, and lung strength become easier to measure than they are in a toddler — and to track their breathing with proper lung-function tests rather than relying only on parents' recollections of coughs and colds. For now, the message from this two-year follow-up is a hopeful one: a promising way to make a life-saving lung medicine work better in the first days of life does not appear to leave any mark — good or bad — on how children are doing two years on [7].

References

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