Research shows that human-milk-based and cow-milk-based fortifiers perform equally well in preventing serious intestinal disease in extremely premature infants. In a Gram Research analysis of 703 babies, necrotizing enterocolitis occurred in 9.5% of those receiving human-milk fortifier versus 6.5% receiving cow-milk fortifier—a difference that wasn’t statistically significant, suggesting both fortifier types are comparably safe.
Extremely premature babies (born before 28 weeks) need special nutrition to grow. Doctors add fortifiers—nutrient boosters—to breast milk to make it stronger. This study compared two types: fortifiers made from human milk versus fortifiers made from cow milk. Researchers looked at 703 tiny babies at two hospitals to see which fortifier better protected them from a serious intestinal disease called necrotizing enterocolitis (NEC). Surprisingly, according to Gram Research analysis, both types of fortifiers performed similarly, with no clear winner in preventing this dangerous condition.
Key Statistics
A 2026 cohort study of 703 extremely premature infants found that human-milk-based fortifiers resulted in necrotizing enterocolitis in 9.5% of babies compared to 6.5% with cow-milk-based fortifiers, with no statistically significant difference between groups.
Among 703 extremely premature infants tracked across two hospitals, surgical intervention rates for necrotizing enterocolitis and mortality rates showed no meaningful differences between babies fed human-milk fortifier versus cow-milk fortifier.
A retrospective analysis of 703 extremely premature infants found an adjusted odds ratio of 1.48 (95% CI: 0.83-2.63) for necrotizing enterocolitis with human-milk versus cow-milk fortification, indicating no significant protective advantage of human-milk fortifiers.
The Quick Take
- What they studied: Whether adding human-milk-based fortifiers to breast milk is better than cow-milk-based fortifiers at preventing a serious gut disease in extremely premature babies
- Who participated: 703 extremely premature infants (born before 28 weeks of pregnancy) from two hospitals: 355 babies received cow-milk fortifier and 348 babies received human-milk fortifier
- Key finding: Gut disease occurred in 9.5% of babies given human-milk fortifier versus 6.5% of babies given cow-milk fortifier—a difference that wasn’t statistically significant, meaning it could have happened by chance
- What it means for you: If you have an extremely premature baby, both types of fortifiers appear equally safe. Talk with your medical team about which option works best for your situation, as other factors beyond disease prevention may influence the choice
The Research Details
This was a retrospective cohort study, meaning researchers looked backward at medical records of babies who had already been born and treated. They compared two groups of extremely premature infants from two different hospitals: one hospital used cow-milk-based fortifiers while the other used human-milk-based fortifiers. Both hospitals followed similar feeding protocols (the same basic feeding plans), which made the comparison fairer. The researchers tracked whether babies developed necrotizing enterocolitis (a serious intestinal infection), whether they needed surgery, and whether they survived.
The study included 703 babies total—355 at one hospital and 348 at the other. The researchers made sure the two groups were similar in important ways at the start, so differences in outcomes would more likely come from the fortifier type rather than other factors. They then compared the rates of disease and death between the two groups.
This research approach is important because extremely premature babies are very fragile and at high risk for serious infections. Finding the safest nutrition strategy could save lives. By comparing two real-world hospital groups using similar feeding plans, the study shows what actually happens in clinical practice rather than just in controlled laboratory settings. This makes the findings more relevant to real babies and real doctors making feeding decisions.
This study has several strengths: it included a large number of babies (703), compared similar groups at two different hospitals, and tracked important health outcomes. However, because it looked backward at existing medical records rather than randomly assigning babies to different fortifiers, we can’t be completely certain the fortifier type caused any differences. The study also couldn’t control for every possible difference between hospitals. The results showed no statistical difference between groups, which is reassuring but means we can’t confidently say one fortifier is better than the other.
What the Results Show
The main finding was that both types of fortifiers resulted in similar rates of necrotizing enterocolitis. Among babies fed human-milk fortifier, 9.5% developed the disease, compared to 6.5% of babies fed cow-milk fortifier. While the human-milk group had a higher percentage, this 3-percentage-point difference was not statistically significant (p = 0.18), meaning it could easily have occurred by random chance rather than because of the fortifier type.
When researchers adjusted for other factors that might affect disease risk, the difference remained non-significant. The adjusted odds ratio was 1.48, with a confidence interval of 0.83-2.63. In plain language, this means that if there is a true difference between the fortifiers, it’s likely small enough that we can’t reliably detect it with this study size.
The researchers also looked at more severe cases requiring surgery and found no differences between groups. Similarly, death rates were comparable between babies receiving each fortifier type. The age at which babies developed the disease, when it occurred, was also similar between groups.
Beyond the main disease outcome, the study examined surgical interventions for necrotizing enterocolitis and found no meaningful differences between the two fortifier groups. Mortality rates—how many babies survived—were also similar regardless of which fortifier they received. These secondary findings support the primary conclusion that both fortifier types appear equally safe for extremely premature infants. The timing of disease onset was also comparable, suggesting neither fortifier accelerated or delayed the condition.
Previous research has suggested that human-milk-based products might offer advantages for premature babies because they’re closer to natural breast milk. Some earlier studies hinted that human-milk fortifiers could reduce infection risk. However, this study’s findings suggest that modern cow-milk-based fortifiers are equally effective at preventing necrotizing enterocolitis. The results align with growing evidence that both fortifier types can support healthy growth in extremely premature infants when used properly. This doesn’t mean human-milk fortifiers are worse—it means they’re not clearly better at preventing this specific serious infection.
This study has important limitations to consider. First, it was retrospective, meaning researchers looked at past records rather than randomly assigning babies to fortifier types. This makes it harder to prove that the fortifier caused any differences. Second, the two hospital groups might have differed in ways not captured in the data—different staff training, different infection control practices, or different patient populations. Third, the study couldn’t detect small differences between fortifiers; a larger study might find meaningful differences that this one missed. Finally, the results apply specifically to extremely premature infants and may not apply to less premature babies or full-term infants.
The Bottom Line
Based on this research, both human-milk-based and cow-milk-based fortifiers appear safe and effective for extremely premature infants. The choice between them should be made by your medical team based on availability, cost, and other clinical factors rather than disease prevention alone. This is a moderate-confidence recommendation based on a single large study; more research would strengthen confidence in these findings.
Parents and doctors caring for extremely premature infants (born before 28 weeks) should pay attention to this research. It’s particularly relevant for neonatal intensive care units deciding which fortifier to stock. The findings may not apply to moderately premature babies or full-term infants, so don’t assume the same conclusions hold for less premature newborns.
Necrotizing enterocolitis typically develops within the first few weeks of life in premature infants. If your baby is receiving fortified breast milk, you should see stable growth and feeding tolerance within days to weeks. Watch for warning signs like feeding intolerance, abdominal swelling, or blood in stool, and report these immediately to your medical team.
Frequently Asked Questions
Is human milk fortifier better than cow milk fortifier for premature babies?
This study found no significant difference between the two types. Both human-milk and cow-milk fortifiers resulted in similar rates of serious intestinal disease in extremely premature infants, suggesting both are equally safe options for nutrition.
What is necrotizing enterocolitis and why does it matter in premature babies?
Necrotizing enterocolitis (NEC) is a serious infection of the intestines that can occur in premature babies. It can require surgery and can be life-threatening. This study examined whether fortifier type affects NEC risk in extremely premature infants.
Should I request human milk fortifier for my extremely premature baby?
Based on this research, there’s no clear advantage to requesting human-milk fortifier over cow-milk fortifier for preventing serious intestinal disease. Discuss with your medical team which option is available and best suited for your baby’s individual needs.
How many babies were studied and how reliable are these results?
The study included 703 extremely premature infants from two hospitals. While this is a large sample, the retrospective design means we can’t completely prove the fortifier type caused any differences. The results are moderately reliable but would benefit from additional research.
Does this research apply to all premature babies or just extremely premature ones?
This study specifically examined extremely premature infants born before 28 weeks of pregnancy. The findings may not apply to moderately premature or full-term babies, so consult your doctor about whether these results are relevant to your situation.
Want to Apply This Research?
- If using a neonatal tracking app, record the type of fortifier used daily and monitor feeding tolerance (volume accepted, residuals, stool patterns) to identify any individual response differences
- Work with your medical team to establish a consistent feeding protocol and track your baby’s response to the chosen fortifier through daily weight gain, feeding volumes, and digestive tolerance
- Maintain a feeding log noting fortifier type, volumes tolerated, and any digestive symptoms. Share this with your care team weekly to ensure optimal nutrition and early detection of any feeding issues
This research applies specifically to extremely premature infants (born before 28 weeks of pregnancy) and should not be applied to other populations without medical guidance. The choice of fortifier should always be made in consultation with your neonatal care team based on your baby’s individual medical needs, hospital protocols, and available resources. This article summarizes research findings and is not a substitute for professional medical advice. Always follow your doctor’s recommendations regarding your baby’s nutrition and care.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.