Can a Sugar From Breast Milk Be Safely Added for Premature Babies? A First Small Trial of 2′-Fucosyllactose

A plain-language look at Mezoff and colleagues' 2026 Nutrients study of a milk sugar given to babies born at 26–31 weeks

Breast milk contains special sugars that babies cannot digest but that help their gut and immune system. In a small randomized study of 42 premature babies in three hospitals in Columbus, Ohio, researchers gave some babies one of those sugars, called 2′-fucosyllactose (or 2′-FL), and gave the others a harmless look-alike. The babies given 2′-FL grew the same as the other babies and had no more side effects, but the study was far too small to show whether the sugar helps, so it does not change how premature babies are fed today [1].

Why breast milk matters so much for premature babies

When a baby is born many weeks early, feeding becomes one of the most important and delicate parts of care. The gut is still maturing, and the most dangerous feeding-related illness is necrotizing enterocolitis, or NEC, in which part of the bowel becomes inflamed and can be damaged. It happens mostly to the smallest, most premature babies, and usually in the first weeks after birth [2].

For many years, doctors and nurses have encouraged mothers of premature babies to provide their own milk whenever they can, and to use carefully screened, pasteurized donor milk if mother's milk is not available. Medical groups recommend this because studies have found that premature babies fed human milk tend to have fewer complications than babies fed formula [3], [4]. Neonatal teams therefore put a great deal of effort into helping mothers pump and store milk, even when it is emotionally and physically exhausting.

The hidden ingredient: milk sugars that feed the right bacteria

Scientists have long wondered what in breast milk does the protecting. One answer is a group of complex sugars called human milk oligosaccharides, or HMOs. After lactose and fat, they are the next biggest solid part of human milk, yet babies do not digest them. Instead, they act like food for helpful gut bacteria, like decoys that stop germs from sticking to the gut wall, and like messengers that calm inflammation [5].

The amount of these sugars in a mother's milk is not fixed. Studies of milk from mothers of premature babies show that the mixture changes during the first month of breastfeeding [6]. One of the most common of these sugars is 2′-FL, and reviews of the research describe it as helping the gut barrier, fighting infection and perhaps supporting brain development [7].

What was already known before this study

Companies already add 2′-FL to formula for healthy full-term babies. In one study, babies fed a formula with 2′-FL grew like breastfed babies [8], and in another, it helped healthy bacteria grow in the gut of formula-fed babies [9].

Experiments in young animals gave an even more interesting hint. In laboratory models of NEC, 2′-FL improved blood flow to the bowel and lessened the damage [10], and together with another milk sugar it calmed an inflammatory signal that contributes to the disease [11]. Researchers also learned that NEC involves a form of cell death called necroptosis, which may be one way these sugars help [12].

Animals are not babies, though, and babies born very early differ from healthy full-term babies in many ways. Before this study, according to the authors, only one other study had given a milk-sugar supplement to premature babies, and nobody had tested 2′-FL by itself or looked at how the babies behaved afterward. So the next step was a careful, first-stage test.

How the study worked

Because this was a "pilot" study, its main goal was to find out whether a bigger study would be possible and safe, not to prove the sugar works [13]. Forty-four babies born between 26 and 31 weeks of pregnancy were enrolled between 2018 and 2023 at three hospitals in Columbus, Ohio; 42 received the study product. Babies with serious problems, such as birth defects, infection, bleeding in the brain, or the need for a breathing machine, were not included.

Which baby got what was decided by chance, like a coin toss, and neither the families nor the staff knew who got which. Twenty-three babies received 2′-FL, which was mixed with water and given by mouth or feeding tube in two small doses a day, for a total of 270 milligrams, a little over a quarter of a gram. Nineteen babies received a placebo, a harmless sugar-water that looked the same. Both groups continued receiving the usual milk feeds and routine NICU care.

The researchers measured each baby's weight every day, and length and head size every week, and compared them with standard growth charts for premature babies [14]. They also counted stools and recorded any health problems. For a smaller group of babies who were stable enough, they tested behavior using a standard 30-minute examination that looks at things like how well a baby can calm itself and pay attention.

What the researchers found

Growth was very similar. Weight, length, and head size increased at similar rates in babies who received the sugar and babies who received placebo. Head size showed a small trend toward being larger with 2′-FL, but the difference was no bigger than could happen by chance. Stool patterns were similar, too [1].

Premature babies in the NICU have many ups and downs, and the researchers recorded 273 mild or moderate health events among the 42 babies, such as brief drops in oxygen, a slow heartbeat, or pauses in breathing. These happened about equally often in both groups. For example, a brief drop in oxygen occurred in 16 of 23 babies (70%) who received 2′-FL and in 12 of 19 (63%) who received placebo [1].

Four more serious events were recorded. Three occurred in placebo babies and one in a baby who received 2′-FL. That baby, born at 29 weeks, began the supplement on day 11 and, three days later, vomited and had blood in the stool. The doctors stopped the supplement, paused feeds, and gave antibiotics because NEC was a worry. The X-rays never showed the telltale signs of NEC, and the baby recovered fully. The team did not think the supplement was the cause when they reported it, and NEC was never confirmed [1].

For the behavior tests, only 24 babies were stable enough to take part, 16 who had 2′-FL and 8 who had placebo. Scores were within the expected range for babies this age. The 2′-FL group had slightly lower scores on one measure of self-calming, but with so few babies, the researchers said it could not be interpreted. Such tests are interesting because they can be associated with how premature babies develop later [15], but this one was an extra, exploratory look, not the main goal.

What this means for families

The honest answer is "not yet." The study was meant to include 90 babies, but because of delays during the COVID-19 pandemic and a supplement manufacturing problem, only 42 were included. A study this small can notice large problems but can miss uncommon ones, and it cannot show whether the sugar prevents illness. In addition, the babies were relatively healthy, and mothers' milk, donor milk, and formula were sometimes mixed, which makes the results harder to read. The study was funded by a company that makes infant nutrition products, and some authors worked for it, though the authors say the academic investigators made the final decisions.

For parents, the key message is that the best-proven way to feed a premature baby has not changed. Mother's own milk, if you are able to provide it, remains the first choice, and donor milk is a trusted second choice. If your baby's team mentions milk sugars or additives, they are a topic of active research, not something to ask for or buy on your own. Our related articles on donor milk for moderately and late preterm babies and early human milk volume and the gut microbiome may be helpful.

Parents sometimes feel pressure to do something extra for a baby who is so small, and it is natural to wonder whether an added ingredient might tip the odds. A useful way to think about this study is as a first safety check, like a test drive before a long road trip: it tells researchers the car starts and runs smoothly, not how well it will perform on the highway. Your baby's care team can explain which feeding choices have strong evidence behind them and which are still being tested, and asking those questions is always welcome.

What researchers are working on next

The authors say larger, longer studies are needed. Researchers would like to start the sugar with a baby's very first feeds, follow babies until they are 18 to 24 months old to see how they develop, measure how much of these sugars babies get from their own mothers' milk, and include babies who are formula-fed or who have had bowel surgery. A trial large enough to count NEC cases will be the real test. Until then, this small study offers some reassurance that the sugar can be given safely to a few babies, along with a good reason to keep looking.

References

  1. Mezoff EA, Duan Q, Ollberding NJ, Reverri EJ, Buck RH, Barrett-Reis B, et al. 2′-Fucosyllactose effects on preterm growth, tolerance, and neurobehavior: a double-blind, randomized, placebo-controlled pilot. Nutrients. 2026;18(15):2437. doi:10.3390/nu18152437 ↩
  2. Yee WH, Soraisham AS, Shah VS, Aziz K, Yoon W, Lee SK, et al. Incidence and timing of presentation of necrotizing enterocolitis in preterm infants. Pediatrics. 2012;129(2):e298-e304. doi:10.1542/peds.2011-2022 ↩
  3. Miller J, Tonkin E, Damarell RA, McPhee AJ, Suganuma M, Suganuma H, et al. A systematic review and meta-analysis of human milk feeding and morbidity in very low birth weight infants. Nutrients. 2018;10(6):707. doi:10.3390/nu10060707 ↩
  4. Parker MG, Stellwagen LM, Noble L, Kim JH, Poindexter BB, Puopolo KM, et al. Promoting human milk and breastfeeding for the very low birth weight infant. Pediatrics. 2021;148(5):e2021054272. doi:10.1542/peds.2021-054272 ↩
  5. Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012;22(9):1147-1162. doi:10.1093/glycob/cws074 ↩
  6. Gabrielli O, Zampini L, Galeazzi T, Padella L, Santoro L, Peila C, et al. Preterm milk oligosaccharides during the first month of lactation. Pediatrics. 2011;128(6):e1520-e1531. doi:10.1542/peds.2011-1206 ↩
  7. Hill DR, Chow JM, Buck RH. Multifunctional benefits of prevalent HMOs: implications for infant health. Nutrients. 2021;13(10):3364. doi:10.3390/nu13103364 ↩
  8. Marriage BJ, Buck RH, Goehring KC, Oliver JS, Williams JA. Infants fed a lower calorie formula with 2′FL show growth and 2′FL uptake like breast-fed infants. J Pediatr Gastroenterol Nutr. 2015;61(6):649-658. doi:10.1097/mpg.0000000000000889 ↩
  9. Lazarini T, Tonon KM, Araujo Filho HB, Morais MB. Bifidogenic effect of 2′-fucosyllactose (2′-FL) on the gut microbiome of healthy formula-fed infants: a randomized clinical trial. Nutrients. 2025;17(6):973. doi:10.3390/nu17060973 ↩
  10. Good M, Sodhi CP, Yamaguchi Y, Jia H, Lu P, Fulton WB, et al. The human milk oligosaccharide 2′-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine. Br J Nutr. 2016;116(7):1175-1187. doi:10.1017/s0007114516002944 ↩
  11. Sodhi CP, Wipf P, Yamaguchi Y, Fulton WB, Kovler M, Niño DF, et al. The human milk oligosaccharides 2′-fucosyllactose and 6′-sialyllactose protect against the development of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling. Pediatr Res. 2021;89(1):91-101. doi:10.1038/s41390-020-0852-3 ↩
  12. Werts AD, Fulton WB, Ladd MR, Saad-Eldin A, Chen YX, Kovler ML, et al. A novel role for necroptosis in the pathogenesis of necrotizing enterocolitis. Cell Mol Gastroenterol Hepatol. 2020;9(3):403-423. doi:10.1016/j.jcmgh.2019.11.002 ↩
  13. Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. Pilot Feasibility Stud. 2016;2:64. doi:10.1186/s40814-016-0105-8 ↩
  14. Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013;13:59. doi:10.1186/1471-2431-13-59 ↩
  15. El-Dib M, Massaro AN, Glass P, Aly H. Neurobehavioral assessment as a predictor of neurodevelopmental outcome in preterm infants. J Perinatol. 2012;32(4):299-303. doi:10.1038/jp.2011.100 ↩