Research shows that human milk-based fortifiers do not provide clear advantages over cow milk-based fortifiers when premature babies receive the same human milk diet. However, a 2026 meta-analysis of nine studies found that human milk-based fortifiers reduced serious intestinal infections by 55 percent when combined with donor human milk instead of formula. According to Gram Research analysis, the overall feeding strategy matters more than the fortifier type alone.
Researchers compared two types of protein additives used to boost nutrition in breast milk for premature babies. One type comes from human milk, while the other comes from cow’s milk. According to Gram Research analysis of nine studies, both types appear equally safe and effective when babies receive the same human milk diet. However, when premature babies got donor human milk instead of formula to supplement their mother’s milk, the human milk-based fortifier showed better protection against a serious intestinal infection. The findings suggest that what babies eat overall matters more than which fortifier is used.
Key Statistics
A 2026 meta-analysis of nine randomized controlled trials found that human milk-based fortifiers reduced necrotizing enterocolitis by 55 percent compared to cow milk-based fortifiers when premature babies received donor human milk supplementation instead of formula.
In studies comparing fortifier types alone with identical diets, human milk-based fortifiers showed no statistically significant reduction in mortality or serious intestinal infections in premature infants, according to the 2026 Nutrients meta-analysis.
The 2026 systematic review identified that benefits of human milk-based fortifiers only appeared when combined with an exclusive human milk feeding strategy, suggesting the overall diet composition matters more than fortifier type.
The Quick Take
- What they studied: Whether human milk-based fortifiers work better than cow milk-based fortifiers for premature babies who are being fed breast milk
- Who participated: Nine research studies involving approximately 1,200 premature or very low birth weight infants from hospitals around the world
- Key finding: When premature babies received only human milk products (fortified breast milk plus donor milk), the human milk-based fortifier reduced serious intestinal infections by 55 percent compared to the cow milk-based version. However, when comparing just the fortifiers alone with the same diet, there was no clear difference between the two types.
- What it means for you: If you have a premature baby in the hospital, both types of fortifiers appear safe. The choice may matter less than ensuring your baby receives human milk products rather than formula when possible. Talk with your baby’s medical team about what’s best for your specific situation.
The Research Details
Researchers conducted a systematic review and meta-analysis, which means they searched medical databases for all high-quality studies comparing human milk-based fortifiers to cow milk-based fortifiers in premature infants. They found nine randomized controlled trials, the gold standard type of research study. Two independent reviewers checked each study to make sure it was reliable and extracted the important information.
The researchers separated the studies into two groups. One group compared just the fortifier types while keeping everything else the same, meaning both groups of babies got the same human milk diet. The other group of studies tested both the fortifier type and what babies received when their mother’s milk wasn’t enough, either donor human milk or formula.
The team used statistical methods to combine results across studies and rated how confident they were in each finding using a system called GRADE, which helps readers understand whether results are strong or uncertain.
This research approach is important because premature babies have very fragile digestive systems and need the best nutrition possible. By combining results from multiple studies, researchers can see patterns that might not show up in a single study. Separating the studies into two groups was especially smart because it helped the team figure out whether benefits came from the fortifier itself or from using human milk products instead of formula.
This meta-analysis included only randomized controlled trials, which are considered the most reliable type of research. The researchers had two people independently review each study to reduce mistakes. However, the studies were relatively small, and some results had low certainty ratings, meaning researchers weren’t completely confident in those findings. The fact that benefits only appeared in one group of studies suggests the results need confirmation with larger, future research.
What the Results Show
When researchers compared the two fortifier types while keeping the rest of the diet identical, human milk-based fortifiers did not reduce death rates or a serious intestinal infection called necrotizing enterocolitis (NEC). The death rate reduction appeared to be 40 percent lower with human milk fortifiers, but this could have happened by chance, so researchers rated this finding as low certainty.
However, in studies where premature babies received donor human milk to supplement their mother’s milk instead of preterm formula, the human milk-based fortifier showed a real benefit. Babies receiving human milk-based fortifiers had 55 percent fewer cases of necrotizing enterocolitis, a serious infection that can damage the intestines. Researchers rated this finding as moderate certainty, meaning they were reasonably confident in this result.
The key insight is that the benefit appeared to come from using human milk products throughout the baby’s diet, not just from the fortifier type alone. When babies received formula to supplement their mother’s milk, the type of fortifier didn’t seem to matter as much.
The research did not identify major safety concerns with either fortifier type. Both appeared well-tolerated by premature babies. The studies did not consistently report on other important outcomes like growth rates, feeding tolerance, or long-term development, so researchers could not draw conclusions about these areas.
Previous smaller studies suggested human milk-based fortifiers might be superior, but this comprehensive review of all available evidence shows the picture is more complex. The findings align with growing research showing that an exclusive human milk feeding strategy, meaning using only human milk products rather than formula, may provide benefits for premature babies. This meta-analysis clarifies that the fortifier type alone doesn’t explain those benefits.
The included studies were relatively small, which means results could be affected by chance. Some studies had design issues that could bias results. The researchers could not find enough data on many important outcomes like how well babies grew or how they developed over time. The studies were conducted in different countries with different practices, which might affect how results apply to your specific situation. Future research with larger sample sizes and longer follow-up periods would strengthen the evidence.
The Bottom Line
Based on moderate-certainty evidence, if your premature baby needs supplementation beyond your breast milk, using donor human milk with a human milk-based fortifier appears to offer the best protection against serious intestinal infections. If donor human milk is not available, both fortifier types appear safe when combined with formula supplementation, though the evidence is less certain. Work with your baby’s medical team to determine the best feeding plan for your individual situation.
Parents of premature or very low birth weight infants should care about this research, particularly those planning to breastfeed or use breast milk. Neonatal intensive care unit (NICU) staff and pediatricians making feeding decisions for premature babies should consider these findings. This research does not apply to full-term babies or babies who are not receiving breast milk.
Benefits like reduced intestinal infections would appear within the first weeks of life while the baby is still in the hospital. Long-term effects on growth and development would take months to years to fully evaluate, which is why future research is needed.
Frequently Asked Questions
Is human milk fortifier better than cow milk fortifier for premature babies?
Not necessarily. Research shows both types are equally safe when babies receive the same diet. However, human milk fortifier combined with donor milk showed 55 percent fewer intestinal infections than cow milk fortifier with formula supplementation.
What should I feed my premature baby in the NICU?
Work with your NICU team on a personalized plan. If available, mother’s own milk with human milk-based fortifier and donor milk supplementation appears optimal. Both fortifier types are safe, so availability and your baby’s tolerance matter.
Does the type of fortifier affect premature baby growth?
The research did not provide clear data on growth differences between fortifier types. Both appear safe and support adequate nutrition. Your baby’s medical team can monitor growth and adjust feeding as needed.
Can human milk fortifier prevent intestinal infections in premature babies?
When combined with donor human milk instead of formula, human milk-based fortifier reduced serious intestinal infections by 55 percent in research studies. The benefit appears linked to using human milk products throughout the diet.
What if donor human milk is not available for my premature baby?
Both fortifier types are safe with formula supplementation. Work with your NICU team to access donor milk if possible, as research suggests it provides additional protection. Either way, your baby will receive adequate nutrition.
Want to Apply This Research?
- If you have a premature baby in the NICU, track the type of fortifier used, the percentage of feeds that are mother’s own milk versus donor milk versus formula, and any feeding tolerance issues. Record this daily to share with your medical team.
- Work with your NICU team to establish and maintain a breast milk pumping schedule if you plan to provide your own milk. Ask specifically about the availability of donor human milk as a supplement option, as this research suggests it may offer additional benefits.
- Monitor your baby’s feeding progress, weight gain, and any signs of digestive distress. Keep detailed records of what your baby receives at each feeding. After discharge, continue tracking growth and development milestones, as long-term outcomes are important for premature babies.
This article summarizes research findings and should not replace medical advice from your pediatrician or neonatal care team. Feeding decisions for premature infants require individualized assessment based on your baby’s specific medical condition, available resources, and your family’s circumstances. Always consult with your baby’s healthcare providers before making changes to feeding plans. This research applies specifically to premature and very low birth weight infants and does not apply to full-term babies.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.