Japanese Trial Shows Human Milk-Based Fortifiers Improve Growth in Extremely Premature Infants

A landmark clinical trial published in the Journal of Perinatology may reshape neonatal nutrition practices in Japan and beyond.

The multicenter JASMINE trial found that extremely premature infants fed with Prolacta Bioscience’s 100% human milk-based fortifiers achieved significantly faster growth, reached full feeding volumes earlier, and required fewer days of antibiotics compared to infants receiving Japan’s current standard nutritional approach.

The findings address one of neonatal medicine’s most difficult challenges: how to provide adequate nutrition to highly vulnerable preterm infants without increasing the risk of necrotizing enterocolitis (NEC), a potentially fatal gastrointestinal disease.

Why Japan’s Neonatal Nutrition Strategy Matters?

Japan is internationally recognized for its exceptional survival outcomes in extremely premature infants. According to the study:

• 80–90% of infants born at 22–24 weeks’ gestation survive to discharge
• Japan maintains NEC rates below 2%
• Clinicians have historically minimized or delayed the use of cow milk-based fortifiers (CMBF) to reduce complications

While this cautious approach helped reduce NEC risk, it also created unintended nutritional limitations for infants during the most critical stages of brain and body development.

Lead author Katsumi Mizuno explained that many Japanese NICUs avoid early feeding until maternal milk becomes available, potentially compromising growth and neurodevelopment.

He also noted that clinicians frequently avoid cow milk-derived fortifiers in very low birth weight infants with gastrointestinal complications, further limiting nutritional intake.

What the JASMINE Trial Evaluated?

The Japanese-led JASMINE study was a randomized, controlled, open-label, multicenter trial conducted across 11 neonatal intensive care units (NICUs).

Researchers compared:

• An Exclusive Human Milk Diet (EHMD) using Prolacta’s human milk-based fortifiers
• Japan’s Standard Diet, which commonly delays or withholds cow milk-based fortification

The protocol included:

• Prolact CR fat modular
• Prolact+6 human milk-based fortifier
• Prolact+8 human milk-based fortifier

In Japan, these products are marketed as PreemieFort Enteral Solution.

Key Clinical Findings

The results showed meaningful improvements in infant growth and feeding progression.

Faster Weight Gain

Infants receiving the Exclusive Human Milk Diet demonstrated:

• Weight gain velocity of 13.44 vs. 11.96 g/kg/day in the intent-to-treat analysis
• Even stronger results in the per-protocol analysis:
  • 14.30 vs. 11.96 g/kg/day
  • p < 0.0001

Improved Length Growth

The EHMD group also showed significantly better length gain velocity:

• 0.85 vs. 0.66 cm/week
• p = 0.0016

Earlier Achievement of Full Feeds

Infants receiving the human milk-based diet reached clinically appropriate feeding volumes faster:

• 20.0 days vs. 25.9 days
• p = 0.03

Reduced Antibiotic Exposure

Researchers also observed significantly fewer days on antibiotics in the EHMD group:

• Adjusted p = 0.002

Importantly, the study reported that the safety profile remained consistent with Japan’s stringent neonatal care expectations.

Why These Results Are Especially Significant?

One detail makes the findings even more compelling. The EHMD group included twice as many extremely premature infants born at 22–23 weeks’ gestation compared to the Standard Diet group:

• EHMD: 10 infants
• Standard Diet: 5 infants

These infants typically face the highest clinical risks, making the improved growth outcomes particularly noteworthy.

The Role of Human Milk Fat and HMOs

A major component of the JASMINE protocol was Prolact CR, a human milk-derived fat modular. More than 95% of infants in the EHMD group received Prolact CR, which contains:

• 25% human milk fat
• Intact milk fat globules (MFGs)

These intact fat structures are believed to play a critical role in delivering nutrients essential for early brain development. In addition, Prolacta’s fortifiers contain high concentrations of:

• Human milk oligosaccharides (HMOs)
• Immunoglobulin A
• Epidermal growth factor

Compared to cow milk-based products, these bioactive compounds may provide enhanced immune and gastrointestinal support for premature infants.

Long-Term Neurodevelopment Implications

The neonatal period represents the fastest phase of brain growth in human life. Because of this, early nutritional strategies can have lifelong consequences for:

• Cognitive development
• Motor function
• Learning ability
• Overall quality of life

According to Melinda Elliott, Japanese clinicians increasingly recognized that improved early growth directly influences long-term neurodevelopmental outcomes.

She credited the work initiated by Dr. Mizuno for helping create a pathway that allows Japanese infants not only to survive, but potentially thrive.

A Potential Shift in Global Neonatal Care

The JASMINE trial adds to growing global evidence supporting exclusive human milk diets in neonatal intensive care settings.

For countries balancing NEC prevention with aggressive nutritional support, the study may provide a new clinical framework for feeding extremely premature infants more effectively without compromising safety.

If adopted more broadly, human milk-based fortification could become an increasingly important strategy in neonatal medicine, particularly for the smallest and most medically fragile infants.