A Milk Protein Was Tested to Protect Premature Babies from Infection — Here's What the Study Found

A plain-language look at the 2025 Aga Khan University trial of bovine lactoferrin for preventing serious infections in premature and low-birth-weight newborns

Premature and small babies are especially vulnerable to a dangerous bloodstream infection called late-onset sepsis — an infection that appears after a baby's first three days of life. Researchers in Pakistan tested whether a natural protein found in breast milk, given as a daily supplement, could help prevent it. The short answer: in this study, it did not clearly help. But the study was small, the babies in it generally did well, and the result does not change the single most valuable thing families and hospitals already know protects babies: breast milk itself [1].

Why This Question Matters

A newborn's immune system is still learning how to defend against germs. In babies born early or born small, that defense is even less developed, and long hospital stays with tubes and lines add more chances for infection to take hold [2]. Sepsis is serious. Across all newborns, roughly 2 in 100 who develop it die — but among premature and low-birth-weight babies, that number rises to around 20 in 100, and babies who survive can face challenges with development as they grow [3]. This danger is heaviest in lower-income countries, where more babies are born early and where good care can be harder to reach [4]. Because of all this, doctors have spent decades searching for a simple, affordable way to stop these infections before they start.

The History Behind the Research

For years, one candidate kept rising to the top of that search: lactoferrin. Lactoferrin is a protein naturally present in colostrum (the first milk) and in mature breast milk. In the laboratory it fights microbes and helps steer the immune system, and studies have noticed that babies who take in more lactoferrin through their mother's milk tend to have fewer infections [5], [6]. A cow-derived version of the protein, called bovine lactoferrin, is inexpensive, can be given by mouth, and is easy to produce — which made it especially appealing for the very places that need it most.

The story since then has been one of hope followed by caution. Some early, smaller studies — including one in India — suggested the supplement might protect babies from infection [7]. But two much larger, carefully run trials — one in the United Kingdom called ELFIN and one led from Australia called LIFT — did not find a clear benefit [8], [9]. When experts pooled all the evidence together, they concluded it simply was not strong enough to be sure either way [10]. Two big questions remained: might the supplement still help in poorer regions where infections are far more common, and how much of it should a baby actually get? The new study from Pakistan was built to explore both [1].

What the Researchers Did

The study took place in the newborn intensive care unit of Aga Khan University Hospital in Karachi, Pakistan, working together with the University of Sydney, between July 2019 and August 2020 [1]. It enrolled babies born early (between 28 and about 37 weeks of pregnancy) and weighing between about 1000 and 2500 grams — roughly 2 to 5.5 pounds — who were healthy enough to be feeding by mouth and had no infection at the start.

The 305 babies were divided at random into three equal groups. One group received a harmless placebo (a sugar powder with no active ingredient), one received 150 milligrams of bovine lactoferrin, and one received 300 milligrams — each mixed into a small amount of breast milk once a day for 28 days. This kind of study is considered the gold standard because it was "double-blind": neither the parents, nor the nurses, nor the doctors judging the results knew which babies got the real supplement and which got the placebo. That prevents expectations from coloring the findings. The researchers went to real lengths to keep the groups comparable and the study fair: a computer assigned babies to the three groups by chance, the sachets looked and dissolved identically so no one could guess their contents, and the team followed each baby with weekly check-ins for a full month, even counting the returned sachets to see how faithfully the supplement was given. Testing two different doses side by side also let them ask not just whether lactoferrin works, but how much of it a baby would need — a practical question that earlier studies had never settled. The researchers then watched carefully for any signs of infection over those four weeks [1].

What They Found

When the researchers looked at their main measure — all infections combined, whether suspected or confirmed by a blood test — the supplement made no clear difference at either dose [1]. One narrower comparison did stand out at first glance: among infections confirmed by a blood culture, 8 of 102 babies in the placebo group had one, compared with just 1 of 102 in the 150-milligram group. That looks striking, but the researchers and reviewers agree it should not be over-read. It rested on only a small handful of cases, it did not hold up for the main measure, and — tellingly — the higher 300-milligram dose did worse than the lower one, which is the opposite of what you would expect if the supplement were truly working. Taken together, the honest interpretation is that this was a chance finding rather than proof of protection.

The supplement also showed no clear effect on necrotizing enterocolitis, a serious intestinal illness of premature babies, and the two deaths in the study (both in the highest-dose group) were judged unrelated to the treatment. Importantly, no safety problems were linked to the supplement [1].

There is one more crucial detail. The researchers had expected about 1 in 4 babies in the placebo group to develop infection; in reality, fewer than 1 in 12 did. Because so few babies got sick, the study simply wasn't large enough to detect a real benefit even if one existed — the authors say so themselves [1]. The babies did better than predicted, likely because this was a well-equipped hospital with careful infection-screening serving a relatively well-off city population — good news for the babies, but it also meant there was less room for a preventive supplement to prove its worth [4].

What This Means for Families

If your baby is in a NICU, here is the reassuring takeaway: a promising, low-cost supplement was tested thoughtfully and did not clearly help in this study — and nothing about that result changes the care that does protect babies. The strongest evidence in this entire field points back to breast milk itself, which naturally contains lactoferrin along with many other protective factors [5], [11]. Supporting mothers to provide their own milk, using donor milk when needed, careful handwashing and line care, and watching closely for early signs of illness remain the real front line against infection.

It also helps to understand why one study rarely settles a question. A single trial is a snapshot of one group of babies in one place and time. When that group turns out healthier than expected — as happened here, with far fewer infections than the researchers had planned for — the study loses its ability to detect a small benefit, the way a survey of too few people can't reliably reveal a close result. That is different from proving the supplement useless. It means the question is still open, and that the honest scientific response is to design a better, larger study rather than to declare the idea dead. This is also why doctors look at the whole body of evidence — many trials together — rather than pinning a decision on any one result.

Families do not need to ask for or worry about lactoferrin supplements based on this study. If a care team is using them, it is reasonable to ask what the current evidence shows. And parents can take genuine encouragement from the bigger picture: the babies in this trial largely thrived, and the everyday practices already in place in a good NICU are what carry the weight.

What Comes Next

Researchers have not given up on the idea. The natural biology behind lactoferrin is real; the challenge is turning it into a proven benefit through a supplement. The most useful future studies will focus on the babies most likely to be helped — the smallest, earliest babies, in places where infections are most common and breast milk is hardest to obtain — use a single well-chosen dose, and keep following babies after they go home, since some infections in this study may have been missed once families left the hospital [1]. Until those studies are done, the best protection remains what it has always been: a mother's milk, clean and careful hospital routines, and a watchful medical team [2].

This article summarizes a single research study for a general audience. It is not medical advice. Decisions about your baby's care should always be made with your medical team.

References

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  2. Kollmann TR, Kampmann B, Mazmanian SK, Marchant A, Levy O. Protecting the Newborn and Young Infant from Infectious Diseases: Lessons from Immune Ontogeny. Immunity. 2017;46(3):350–363. doi:10.1016/j.immuni.2017.03.009 ↩
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  7. Kaur G, Gathwala G. Efficacy of Bovine Lactoferrin Supplementation in Preventing Late-onset Sepsis in Low Birth Weight Neonates: A Randomized Placebo-Controlled Clinical Trial. J Trop Pediatr. 2015;61(5):370–376. doi:10.1093/tropej/fmv044 ↩
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  9. Tarnow-Mordi WO, Abdel-Latif ME, Martin A, et al. The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): a multicentre, double-blind, randomised controlled trial. Lancet Child Adolesc Health. 2020;4(6):444–454. doi:10.1016/S2352-4642(20)30093-630093-6) ↩
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