A Common Antibiotic Does Not Protect Premature Babies' Lungs, a Large New Analysis Confirms

What families should know about the 2026 review of six studies testing azithromycin against chronic lung disease of prematurity

A large new analysis has found that azithromycin, a widely used antibiotic, does not prevent the chronic lung disease that affects many babies born very early. Researchers combined the results of six carefully conducted studies involving 1,360 premature infants and found that babies given azithromycin were no less likely to develop the lung condition—or to survive, or to avoid other serious complications—than babies given a placebo [1]. For families whose babies are facing a long stay in the neonatal intensive care unit (NICU), the finding helps clarify what does and does not help protect a fragile newborn's lungs.

Why This Question Matters

Babies born many weeks early have lungs that are not yet finished growing. When these lungs are exposed to the oxygen and breathing support they need to survive, they can become inflamed and scarred, leading to a condition called bronchopulmonary dysplasia, or BPD. Doctors diagnose BPD when a baby still needs extra oxygen at what would have been about 36 weeks of pregnancy [2]. BPD is one of the most common serious complications of prematurity, and it can mean a longer hospital stay, oxygen support at home, and breathing difficulties that last into childhood. Because it is so common and so consequential, researchers have spent decades looking for a medicine that can prevent it—so far with limited success.

It helps to understand why the lungs of a very premature baby are so vulnerable. In the womb, a baby's lungs develop in a low-oxygen environment and are not meant to do the work of breathing until close to a full-term birth. When a baby arrives many weeks early, those delicate, half-built lungs must suddenly take over, often with the help of a ventilator and extra oxygen. Even when this support is delivered as gently as possible, it places stress on tissue that was never ready for it, and inflammation can follow. This is why preventing BPD has proven so difficult: the condition does not come from a single cause that one medicine can switch off, but from the collision of an immature organ with the demands of life outside the womb. Understanding this helps explain why a drug that seemed logical on paper did not work in practice.

The Story Behind the Search

The reason doctors hoped azithromycin might help is worth understanding. Long before a baby is born, infection and inflammation in the womb can set the stage for lung injury [3], [4]. One specific germ, a bacterium called Ureaplasma, can settle in a premature baby's lungs and stir up the kind of inflammation that leads to scarring. Azithromycin is unusual because it does two things at once: it kills bacteria like Ureaplasma, and it also calms inflammation directly. That double action made it a natural candidate, and early, smaller studies seemed encouraging. One review suggested azithromycin lowered the rate of lung disease [5], and another hinted the benefit was strongest in babies who carried Ureaplasma [6]. Guides to caring for these babies listed the drug as a promising but unproven option [7]. In the past, this uncertainty meant that some hospitals occasionally used azithromycin in the hope of protecting the lungs, while others waited for stronger proof.

That stronger proof has now arrived. In 2024, a large study in the United Kingdom called AZTEC gave azithromycin or placebo to nearly 800 premature babies—more than all the earlier studies put together—and found no benefit [8]. The 2026 analysis pooled AZTEC together with the older studies to reach the clearest answer yet.

What the Researchers Found

When all six studies were combined, the numbers told a consistent story. Babies who received azithromycin were about as likely to develop BPD, or to die, as babies who received placebo—the differences were small and could easily have been due to chance [1]. The same was true for a range of other serious problems of prematurity, including bowel injury, bleeding in the brain, and an eye condition that can affect vision. Azithromycin also did not shorten the time babies spent on a breathing machine.

Perhaps most importantly, the researchers looked specifically at babies who carried Ureaplasma—the group most expected to benefit—and still found no advantage. The encouraging signal from the earlier, smaller studies had come mostly from a single older trial [9], and it disappeared once the much larger body of evidence was assembled. Interestingly, a separate study confirmed that azithromycin does succeed in clearing the Ureaplasma germ from the lungs [10]—it simply does not change whether the baby goes on to develop chronic lung disease. In other words, getting rid of the germ was not enough to protect the lungs, which tells doctors that other factors are driving the damage.

What This Means for Your Baby and Family

If your baby is premature and at risk for BPD, this research means that azithromycin is not a treatment you should expect to be offered specifically to protect the lungs. This is not bad news—it is clarity. Knowing that a medicine does not work spares babies from being given a drug with no benefit. And that matters, because antibiotics are not harmless: giving them when they are not needed can upset a baby's developing gut bacteria and contribute to the broader problem of antibiotics becoming less effective over time. Doctors now have good reason to save azithromycin for situations where a baby has a genuine infection that needs it, rather than using it in the hope of preventing lung disease.

It is also worth knowing that this study looked at babies of somewhat different ages and used different doses of the drug across the various trials [11], so scientists cannot completely rule out that some very specific group of babies might respond differently. But the overall pattern was so consistent that a meaningful benefit for most babies is unlikely.

Families sometimes wonder whether a "negative" study like this is a setback. In an important sense, it is the opposite. Medicine advances not only by finding treatments that work but also by clearly identifying those that do not, so that time, effort, and a baby's exposure to medication are not spent on something unhelpful. The studies pooled here were conducted carefully over nearly twenty years, across four countries and hundreds of families who agreed to take part, and their combined answer is trustworthy precisely because it draws on so many babies [1]. If your baby was part of one of these trials, or if you ever consented to research during a NICU stay, that contribution is exactly what made this clear answer possible. Every family who participates in a well-designed study helps the next family receive better, more honest guidance.

If you would like to feel more engaged in your baby's care, it is completely reasonable to ask the medical team which treatments they are using to protect your baby's lungs and what the evidence behind each one is. Good questions include what is being done to keep breathing support as gentle as possible, whether your baby is receiving caffeine or other established therapies, and how the team is supporting nutrition and growth. Asking these questions is not second-guessing the team; it is partnering with them, and most clinicians welcome a parent who wants to understand the plan.

What Researchers Are Working On Next

The end of one avenue opens others. Because BPD is caused by several kinds of injury working together—not just infection—the researchers suggest that future prevention will likely come from combining several strategies rather than relying on any single drug. This is a meaningful shift in thinking. For years, the hope was that a single medicine might act as a kind of shield for the lungs, and azithromycin was one of the most promising candidates because it could both fight infection and calm inflammation [6]. The lesson from this large analysis is that no single medicine is likely to be enough, and that protecting these fragile lungs will depend on many small, careful choices made together—how breathing support is delivered, how infection is prevented and treated, how nutrition is provided, and how growth is supported over weeks and months in the NICU. Scientists are now focusing on treatments that protect the immature lung from the oxidative stress and inflammation that cause scarring. In the meantime, the best protection for a premature baby's lungs remains the careful, day-to-day work of the NICU team: gentle breathing support, good nutrition, and the established treatments that genuinely make a difference. Families can take comfort in knowing that the medical community continues to test each promising idea rigorously, keeping what works and setting aside what does not. That is how progress in newborn care is made—not through a single breakthrough drug, but through the patient accumulation of honest answers, each one making the care of the next premature baby a little safer and a little wiser. If your family is on this journey now, know that the questions still being asked are the right ones, and that the care your baby receives today reflects decades of exactly this kind of careful learning.

References

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  2. Higgins RD, Jobe AH, Koso-Thomas M, et al. Bronchopulmonary dysplasia: executive summary of a workshop. J Pediatr. 2018;197:300–308. doi:10.1016/j.jpeds.2018.01.043 ↩
  3. Villamor-Martinez E, Álvarez-Fuente M, Ghazi AMT, et al. Association of chorioamnionitis with bronchopulmonary dysplasia among preterm infants: a systematic review, meta-analysis, and metaregression. JAMA Netw Open. 2019;2(11):e1914611. doi:10.1001/jamanetworkopen.2019.14611 ↩
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