Friendly Bacteria for the Smallest Babies: How Well Do Probiotics Protect the Premature Gut, and How Safe Are They?

What three 2026 studies from Sweden (Mitha et al.), the Netherlands (Imren et al.) and the United States (Patel et al.), published in JAMA Network Open, tell families about probiotics in neonatal intensive care

Probiotics are powders of live, friendly bacteria that some hospitals give to babies born very early, to help protect the gut from a serious illness called necrotizing enterocolitis. Two 2026 studies from Sweden and the Netherlands found that a carefully made three-strain probiotic was linked to much less of this illness, and a large US study found that infections caused by probiotic-type bacteria were rare: about 1 extra for every 2500 babies given probiotics.

Why a premature baby's gut needs protecting

This article explains three studies by Mitha, Imren, Patel and their colleagues [1][2][3], and why doctors and parents care about them. When a baby is born many weeks early, the gut is not yet ready for life outside the womb. The muscles that move milk along are immature, the lining is thin and leaky, and the body's defenses are still learning. The gut also needs to be settled by the right mix of bacteria, and premature babies can end up with less variety in their gut bacteria, especially after long courses of antibiotics [4]. In some babies, part of the bowel becomes inflamed and can be badly damaged. Doctors call this necrotizing enterocolitis, or NEC ("necrotizing" means tissue dying; "enterocolitis" means inflammation of the bowel). Among babies weighing between 500 and 1500 grams at birth, about 7 in every 100 develop NEC, and 20 to 30 in every 100 babies who get it die, with the highest risk among those who need an operation [4]. Because an unhealthy mix of gut bacteria may play a part in causing NEC, researchers wondered whether adding friendly bacteria could help [5].

How probiotics went from a hopeful idea to a divided world

Over many years, researchers tested probiotics in careful experiments called randomized trials, in which a coin-toss decides which babies get the real product and which get a look-alike. When an independent review group pooled 60 such trials involving 11 156 babies, probiotics appeared to cut the risk of NEC roughly in half and might slightly reduce deaths, although trials in the very smallest babies showed little or no benefit [5]. One important trial, the ProPrems trial (a placebo-controlled trial of the same three-strain probiotic in Australia and New Zealand, meaning babies were compared with others given a look-alike powder), tested the same three-strain combination used in the Swedish and Dutch studies in 1099 babies: NEC affected 2 in every 100 babies who got probiotics compared with about 4 in every 100 who did not [6]. But not every probiotic works. A large trial of a different, single-strain product in 24 hospitals in southeast England found no benefit [7].

Because of this, expert groups gave different advice. In 2020, European children's gut and nutrition specialists suggested that hospitals could consider one of two specific products, including this three-strain one, as long as product quality was guaranteed and their laboratories could detect infections caused by probiotic bacteria [8]. In the United States, where probiotics are sold as dietary supplements rather than medicines, the American Academy of Pediatrics said in 2021 that the evidence did not support giving them routinely to every premature baby, especially those under 1000 grams [9]. Then, in 2023, the US Food and Drug Administration warned that probiotic bacteria can enter a premature baby's bloodstream and cause a dangerous infection, after a premature baby given a probiotic died of such an infection; it also noted that no probiotic has been approved as a medicine for babies [10]. As a result, whether a premature baby received probiotics came to depend heavily on the country and even the hospital where the baby was born. In England and Wales, for example, the share of babies born before 32 weeks who received probiotics rose from 9 in 100 to 54 in 100 between 2016 and 2022 [11]. Many families were left unsure what to believe.

Three studies asking three different questions

The new studies looked at what happens in everyday hospital care rather than in a trial. In Sweden, where the national neonatal society recommended probiotics in 2020, Mitha and colleagues studied babies born between 28 and 31 weeks of pregnancy, using a national register that records every baby admitted to all 38 Swedish neonatal intensive care units. They compared 1571 babies who received the three-strain probiotic with 3124 who did not, all born between 2017 and 2024 [1].

In the Netherlands, two large neonatal units in Rotterdam and Amsterdam began giving the same probiotic every day to all babies born before 30 weeks or weighing under 1000 grams. Imren and colleagues compared 598 babies born before the change with 815 born afterwards. About half the babies in each group were born before 28 weeks, so this was a higher-risk group than in Sweden [2].

In the United States, Patel and colleagues asked a different question: how often do the kinds of bacteria found in probiotics turn up in a baby's blood? They studied records of 107 505 babies born between 22 and 32 weeks in neonatal units across 33 states and Puerto Rico, of whom 19 990 received some probiotic [3].

Much less NEC in Swedish and Dutch babies given probiotics

The two European studies told a similar story about NEC. In Sweden, NEC or death affected about 34 in every 1000 babies who did not get probiotics, but about 8 in every 1000 who did. Serious NEC needing surgery happened in only 1 of the 1571 babies given probiotics, compared with 40 of the 3124 who were not [1]. In the Netherlands, where babies were smaller and sicker, NEC fell from about 12 in every 100 babies before the change to about 5 in every 100 afterwards. The researchers calculated that about 15 babies needed to receive probiotics for one fewer baby to develop NEC [2].

What about survival?

Here the two studies did not agree, and it is important to be honest about that. In Sweden, fewer babies given probiotics died: 4 of 1571, compared with 45 of 3124 [1]. In the Netherlands, the overall number of deaths stayed about the same, at roughly 12 in every 100 babies before and after the change. Fewer babies died of NEC, but deaths from other causes—such as a lung blood-pressure problem called persistent pulmonary hypertension, lack of oxygen around birth, and heart or brain problems—rose from about 7 to about 10 in every 100 babies. The Dutch researchers thought these deaths were mostly unrelated to probiotics but said the finding needs careful watching [2]. The two hospital groups cared for quite different babies, and nobody yet knows why the results differ.

How rare are infections caused by the probiotic itself?

This is the worry behind the US warning, and the new studies help to put it in proportion. In the US study, only 8 of the 19 990 babies given probiotics had probiotic-type bacteria in their blood, compared with 3 of the 87 515 who were not given probiotics. That works out to roughly 1 extra infection for every 2500 babies given probiotics [3]. In the Netherlands, one baby out of the 815 born after the change had one of the probiotic bacteria in the blood while very ill with NEC, and died within hours; doctors could not tell whether the bacteria caused the death [2]. Every Swedish neonatal unit reported no infections caused by the probiotic [1]. An earlier review of published cases found that most babies with such infections recovered with antibiotics or antifungal medicines [12].

What this means for your baby

If your baby is born between 28 and 31 weeks in a unit that uses a well-tested product, these studies suggest probiotics are linked to a meaningfully lower chance of NEC, with a very small risk of infection from the probiotic bacteria. In practice, the probiotic is a small daily dose of powder mixed with a little breast milk or sterile water and given through the feeding tube, usually starting in the first few days of life and stopping when the baby reaches the age at which they would have been about 34 to 35 weeks into the pregnancy, as in the Swedish and Dutch programs [1][2]. It is reasonable to ask your baby's team which product they use, why they chose it, and how they prepare it; the Dutch units, for example, mixed it in a special protective cabinet [2]. For babies born before 28 weeks, the Swedish researchers specifically say their results should not be applied [1], and the evidence is less settled, so this is a good topic for an open conversation with your baby's doctors. The Swedish authors hope their numbers will help families and clinicians make these decisions together. Parents who have lived through NEC share their experiences in the In[Neo]Sight article on the parental perspective of NEC.

What researchers are working on next

The biggest open question is whether probiotics help the very smallest babies. The Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial, run in six neonatal units in Sweden and four in Denmark, plans to include 1620 babies born before 28 weeks and is testing the same three-strain product against a look-alike powder [13]. Experts are also calling for stricter quality standards for probiotic products, to make sure what is on the label is what is in the bottle and that nothing harmful gets in during manufacture [14].

A balanced picture

Together, these three studies show that one carefully made probiotic was linked to much less NEC when used routinely in Swedish and Dutch hospitals, and that infections caused by probiotic bacteria are rare. Whether probiotics also help the smallest babies survive is still being studied, and your baby's care team is the best partner for weighing the benefits and risks for your child.

References

  1. Mitha A, Söderquist Kruth S, Sinervo E, et al. Probiotics and Risk of Death, Necrotizing Enterocolitis, and Sepsis in Very Preterm Infants. JAMA Netw Open. 2026;9(9):e2635560. doi:10.1001/jamanetworkopen.2026.35560 ↩
  2. Imren C, Jongejans V, Onland W, et al. Probiotic Implementation and Necrotizing Enterocolitis Risk in Preterm Infants. JAMA Netw Open. 2026;9(8):e2631601. doi:10.1001/jamanetworkopen.2026.31601 ↩
  3. Patel RM, Bennett MM, Canvasser J, Greenberg RG, Ahmad KA, Tolia VN. Probiotic-Associated Invasive Infection Among Preterm Infants. JAMA Netw Open. 2026;9(7):e2626530. doi:10.1001/jamanetworkopen.2026.26530 ↩
  4. Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. 2011;364(3):255-264. doi:10.1056/NEJMra1005408 ↩
  5. Sharif S, Meader N, Oddie SJ, Rojas-Reyes MX, McGuire W. Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database Syst Rev. 2023;7(7):CD005496. doi:10.1002/14651858.CD005496.pub6 ↩
  6. Jacobs SE, Tobin JM, Opie GF, et al. Probiotic effects on late-onset sepsis in very preterm infants: a randomized controlled trial. Pediatrics. 2013;132(6):1055-1062. doi:10.1542/peds.2013-1339 ↩
  7. Costeloe K, Hardy P, Juszczak E, Wilks M, Millar MR. Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial. Lancet. 2016;387(10019):649-660. doi:10.1016/S0140-6736(15)01027-201027-2) ↩
  8. van den Akker CHP, van Goudoever JB, Shamir R, et al. Probiotics and Preterm Infants: A Position Paper by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Committee on Nutrition and the European Society for Paediatric Gastroenterology Hepatology and Nutrition Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr. 2020;70(5):664-680. doi:10.1097/MPG.0000000000002655 ↩
  9. Poindexter B. Use of Probiotics in Preterm Infants. Pediatrics. 2021;147(6):e2021051485. doi:10.1542/peds.2021-051485 ↩
  10. US Food and Drug Administration. Risk of Invasive Disease in Preterm Infants Given Probiotics Formulated to Contain Live Bacteria or Yeast. FDA safety communication; September 29, 2023. Accessed October 5, 2026. https://www.fda.gov/safety/medical-product-safety-information/risk-invasive-disease-preterm-infants-given-probiotics-formulated-contain-live-bacteria-or-yeast ↩
  11. Aveline A, Szatkowski L, Berrington J, et al. Description of probiotic use in preterm infants in England and Wales 2016-2022. BMJ Paediatr Open. 2025;9(1):e003605. doi:10.1136/bmjpo-2025-003605 ↩
  12. Kulkarni T, Majarikar S, Deshmukh M, et al. Probiotic sepsis in preterm neonates-a systematic review. Eur J Pediatr. 2022;181(6):2249-2262. doi:10.1007/s00431-022-04452-5 ↩
  13. Kruth SS, Willers C, Persad E, Sjöström ES, Lagerström SR, Rakow A. Probiotic supplementation and risk of necrotizing enterocolitis and mortality among extremely preterm infants-the Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial: study protocol for a multicenter, double-blinded, placebo-controlled, and registry-based randomized controlled trial. Trials. 2024;25(1):259. doi:10.1186/s13063-024-08088-8 ↩
  14. Shane AL, Preidis GA. Probiotics in the Neonatal Intensive Care Unit-A Framework for Optimizing Product Standards. JAMA Pediatr. 2023;177(9):879-880. doi:10.1001/jamapediatrics.2023.2165 ↩