One Probiotic or Three? For Very Premature Babies, Children Turn Out the Same Either Way

A long-term study following the SiMPro trial checked whether the type of probiotic given to extremely premature newborns changed how they were doing at school age

When babies are born extremely early, many neonatal units give them a probiotic—friendly gut bacteria—to help protect their fragile intestines, and a long-running study has now checked whether the kind of probiotic makes any lasting difference. Researchers followed a group of children who, as tiny newborns, had been randomly given either a single strain of Bifidobacterium bacteria or a mixture of three strains, and re-examined them at around five to seven years of age. The reassuring answer: children who received one strain and those who received three were developing comparably—in thinking skills, behavior, growth, blood pressure, and allergies alike [1], [2].

Why This Question Matters

Babies born more than three months early—before 28 weeks of pregnancy—start life with organs, including the brain and gut, that are not yet ready for the outside world. Thanks to modern neonatal care, far more of these babies survive than in past decades, but survival is only the beginning. Many face a higher chance of difficulties with learning, movement, attention, and language as they grow. Studies that have followed such children for years consistently find these challenges, from eight-year-olds born at the earliest gestations [3] to large national groups of children tracked across France [4] and Sweden [5]. Anything that might give a premature baby's developing brain a better start is therefore worth investigating carefully.

It helps to know what a probiotic actually is. Probiotics are live, beneficial bacteria—similar to the ones that naturally live in a healthy gut—given deliberately to help tip the balance toward good microbes. In a premature baby, whose gut has barely begun to gather its normal bacterial community, this head start can matter a great deal.

One promising idea centers on the gut. A premature baby's intestine is colonized by bacteria in an unbalanced way—a state called dysbiosis—that has been linked to inflammation and to injury of the developing brain. Over the last fifteen years, doctors learned that giving certain probiotic bacteria can lower the risk of a dangerous bowel disease called necrotizing enterocolitis, reduce feeding problems, and shift the gut toward a healthier balance [6]. Because of this, probiotics became a routine part of care in many units. An earlier long-term study, called ProPrems, had already offered reassurance that probiotics did not harm children's later development, and even hinted at less hearing loss in those who received them [7].

How Families Used to Face This Uncertainty

Here is where a practical puzzle arose. Once probiotics became standard, a new question appeared with no clear answer: which probiotic? Dozens of products exist. Some contain a single type of bacterium; others blend several. It seemed plausible that "more is better"—that a mixture of strains might do more for a baby than one alone. Certain bacteria, such as Bifidobacterium longum infantis, are especially good at digesting the natural sugars in breast milk and turning them into helpful compounds [8], [9], and some gut bacteria produce substances that nourish the gut lining and may support brain development [10]. For years, though, parents and clinicians simply did not know whether choosing a three-strain product over a one-strain product actually helped a child in the long run. Decisions were made on cost, availability, and short-term evidence, with the long-term question left open.

What the Researchers Did

To answer it, researchers turned to a carefully run trial called SiMPro, conducted at a single hospital—King Edward Memorial Hospital in Perth, Western Australia [2]. In that trial, 173 babies born before 28 weeks had been randomly assigned soon after birth to receive either a single-strain probiotic (B. breve M-16V) or a triple-strain probiotic (the same B. breve plus two more Bifidobacterium types). Random assignment matters because it means the two groups were alike in every other way, so any later difference could be credited to the probiotic rather than to chance differences between the children.

Years later, the same children were invited back. Trained specialists who did not know which probiotic each child had received measured their thinking and learning skills, behavior, and problem-solving abilities at about five years old, checked their height, weight, head size, and blood pressure, and asked families about asthma, hay fever, and eczema when the children were six to seven [1]. Keeping assessors "blinded" this way guards against unconscious bias. Impressively, nearly all the eligible children came back—about 89% of the single-strain group and 95% of the triple-strain group—which makes the results trustworthy.

What They Found

On every measure, the two groups looked alike [1]. Thinking and learning scores were similar, and serious learning difficulty was uncommon and no more frequent in one group than the other (about 7% versus 4%, a difference well within the range of chance). Rates of cerebral palsy (around 6% in each group), autism, and hearing or vision problems did not differ. The children's growth—height, weight, and head size—matched closely, sitting right around the average for their age, as did their blood pressure. Reports of asthma, hay fever, and eczema were also comparable between the groups.

A word about how to read a result like this. When researchers find "no significant difference," it does not mean the two groups scored identically down to the last point—a few measures leaned slightly one way or the other. It means the small gaps that did appear were within the range you would expect from ordinary chance and the limited number of children studied, rather than a real, repeatable effect of the probiotic. This study was modest in size and was not primarily designed to detect tiny differences in development, so the fairest summary is straightforward: adding two extra bacterial strains at the start of life did not give children a measurable head start, and did not appear to disadvantage them either, by the time they reached school.

What This Means for Families

For parents, the takeaway is reassuring. If your baby received a probiotic in the neonatal unit, it was chosen for sound reasons, and this study suggests that whether it contained one strain or three, children are developing similarly at school age. Families who have worried that a "simpler" probiotic might have shortchanged their child can set that particular worry down.

There is also comfort in how the study was carried out. It followed real children over five to seven years—not a laboratory measure or a short-term snapshot—and nearly every family who could take part did, which is unusual for studies that run this long. When almost everyone returns, the results are far less likely to be skewed by only the healthiest or the most affected children showing up. That strong participation is a big part of why these particular findings can be trusted, even though the study was small.

It is important to be honest about what the study does not say. Every child in it received a probiotic, so the study compared two products against each other, not against giving no probiotic at all. It also cannot promise that any probiotic erases the real challenges that can come with being born extremely early—those challenges are driven mainly by prematurity itself, which is also why premature children benefit from ongoing checks of development, growth, and blood pressure as they get older [11], [12]. What supports a child most is not a particular brand of bacteria but steady, attentive follow-up care.

What Researchers Are Working On Next

Scientists now want to answer the bigger questions this study opens up: not just "one strain or three?" but which probiotic effects are genuinely real, and for which babies. To do that well, they are calling for large studies across many hospitals, using the same yardsticks for measuring development and combining them with detailed analysis of each baby's gut bacteria. That way, the field can move from reassurance toward precise guidance—matching the right support to the right child. For today, families and clinicians can take comfort in a clear result: for very premature babies, one Bifidobacterium strain or three, the children turn out the same.

References

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  2. Athalye-Jape G, Esvaran M, Patole S, et al. Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trial. BMJ Open Gastroenterol. 2022;9(1):e000811. doi:10.1136/bmjgast-2021-000811 ↩
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