Human Milk Fortification for Premature Infants

Overseen By Bouraa Bou Aram, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Crouse Hospital

Disqualifiers: Chromosomal trisomy, congenital heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 18 months

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how adding a special fortifier to human milk affects extremely premature babies born at or before 27 weeks. The goal is to determine if it aids their growth and development. Two groups participate: one receives the fortifier early, while the other receives it only if the baby isn't gaining enough weight. Suitable candidates are babies admitted to the NICU within their first week and starting their first milk feed. As an unphased trial, this study provides a unique opportunity to enhance understanding and care for extremely premature infants.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

What prior data suggests that this human milk fortification is safe for premature infants?

Research has shown that human milk fortifiers, such as the Human Milk Donor Fortifier, are generally safe for premature babies. These fortifiers aid in the growth of preterm babies and may strengthen their bones. They enhance the nutrition in breast milk, which is crucial for babies born early.

One study found that human milk-based fortifiers did not increase the risk of necrotizing enterocolitis, infections, or death compared to cow's milk-based fortifiers. Another study demonstrated that starting fortification early can help babies grow longer and maintain consistent head size from birth to full term.

Overall, hospitals commonly use human milk fortifiers, and they are considered safe for preterm babies. However, discussing any concerns with healthcare providers involved in the trial is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of Human Milk Donor Fortifier for premature infants because it offers a tailored approach to nutrition that could boost growth and development. Unlike traditional fortification methods that might be more generalized, this approach allows for either early routine fortification when a certain feeding volume is reached or selective fortification based on specific weight gain needs. This personalized method aims to optimize caloric intake more effectively, potentially leading to improved health outcomes for premature infants.

What evidence suggests that this trial's treatments could be effective for premature infants?

This trial will compare two approaches to fortifying human milk for premature infants. Research has shown that adding special nutrients to human milk can greatly benefit very premature babies. One study found that these nutrients reduced the death rate by up to 50% for these fragile infants. Premature babies often need more calories and protein, and these added nutrients provide essential support. Although some studies indicate that these nutrients might not prevent all serious problems, they still play a key role in lowering major health risks. Overall, these added nutrients are important for improving the health and survival of very premature babies. ^{6 7 8 9 10}

Who Is on the Research Team?

Bouraa Bou Aram, MD

Principal Investigator

Crouse Hospital

Swati Murthy, MD

Principal Investigator

Crouse Hospital

Steven J Gross, MD

Principal Investigator

Crouse Hospital

Are You a Good Fit for This Trial?

This trial is for extremely preterm infants born at or before 27 weeks of gestation. They must be admitted to the NICU before they are seven days old and prior to their first feeding. Infants with serious birth defects like chromosomal trisomy, heart issues, or abdominal wall defects cannot participate.

Inclusion Criteria

My baby was born at or before 27 weeks and admitted to the NICU within their first week.

Exclusion Criteria

My infant has a severe birth defect like Down syndrome, heart issues, or abdominal wall problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Randomized controlled trial of early routine vs. selective human milk fortification in extremely preterm infants

18 months

Daily monitoring in NICU

Follow-up

Participants are monitored for growth and neurodevelopmental outcomes after discharge from NICU

2 years

Visits at 6, 15, and 24 months adjusted age

Data & Safety Monitoring

Independent safety monitoring committee reviews safety data periodically

What Are the Treatments Tested in This Trial?

Interventions

• Human Milk Donor Fortifier

Trial Overview The study compares two approaches: routinely adding a Human Milk Donor Fortifier to the diets of these preterm infants versus doing so selectively based on specific needs. The goal is to see how this affects their growth and health outcomes.

How Is the Trial Designed?

Group I: Early Routine Fortification Experimental Treatment 1 Intervention

Human Milk Donor Fortifier added to preterm human milk (maternal or donor) when feeds of 150 ml/kg/day are reached (120Kcal/kg/day)

Group II: Selective Fortification Active Control 1 Intervention

Human Milk Donor Fortifier added to preterm human milk (maternal or donor) only for weight gain less than 15g/kg/day after full feeds of 180 ml/kg/day are achieved (120 Kcal/kg/day). If milk of any infant in the selective fortification group gets fortified the volume will be decreased to 150 ml/kg/day to keep the total caloric intake equal.

Human Milk Donor Fortifier is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Human Milk Fortifier for:

• Nutritional support for preterm infants
• Prevention of nutritional deficits in critically ill infants

Approved in European Union as Human Milk Fortifier for:

• Nutritional support for preterm infants
• Prevention of nutritional deficits in critically ill infants

Approved in Canada as Human Milk Fortifier for:

• Nutritional support for preterm infants
• Prevention of nutritional deficits in critically ill infants

Who Is Running the Clinical Trial?

Crouse Hospital

Lead Sponsor

Trials

3

Recruited

420+

Published Research Related to This Trial

The new ultraconcentrated liquid human milk fortifier (LHMF) significantly improved growth metrics, such as weight and length, in preterm infants compared to a traditional powdered human milk fortifier (HMF) over a 28-day study involving 150 infants.

The LHMF was found to be safe, with no increase in the incidence of serious conditions like sepsis or necrotizing enterocolitis, while also providing about 20% more protein than the control HMF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new liquid human milk fortifier and linear growth in preterm infants. Moya, F., Sisk, PM., Walsh, KR., et al.[2012]

Both Similac Natural Care (NC) and Enfamil Powder (EP) fortifiers provide essential nutritional support for healthy preterm infants, with no significant differences in overall growth outcomes between the two groups during the study.

However, Enfamil Powder showed a significant decrease in alkaline phosphatase and an increase in calcium levels, likely due to its higher vitamin D content, suggesting the need for monitoring these nutrients when using fortifiers long-term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, controlled evaluation of two commercially available human breast milk fortifiers in healthy preterm neonates. Sankaran, K., Papageorgiou, A., Ninan, A., et al.[2019]

The introduction of human milk-based human milk fortifiers (HMB-HMF) in NICUs has shown to reduce comorbidities in very low birth weight (VLBW) infants, including a decrease in rates of necrotizing enterocolitis (NEC), making it a beneficial option for exclusive human milk diets.

Implementing exclusive human milk diet (EHMD) programs in NICUs is cost-effective, with reported annual cost avoidance ranging from $515,113 to $3,369,515 per institution, highlighting the financial benefits alongside improved health outcomes for VLBW infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementing an exclusive human milk diet for preterm infants: real-world experience in diverse NICUs. Swanson, JR., Becker, A., Fox, J., et al.[2023]

Infants receiving acidified liquid human milk fortifier (HMF) were significantly more likely to develop metabolic acidosis compared to those receiving powdered HMF, indicating a safety concern with the liquid form.

Despite higher protein intake in the acidified liquid HMF group, there was no difference in growth rates between the two groups, suggesting that the increased protein did not translate to better growth outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of metabolic acidosis with bovine milk-based human milk fortifiers. Cibulskis, CC., Armbrecht, ES.[2021]

In a study involving seven very low birth weight and preterm infants, the use of a human milk-based human milk fortifier (HMHMF) successfully addressed feeding intolerance caused by a bovine-based human milk fortifier (BHMF).

All infants transitioned off parenteral nutrition without gastrointestinal symptoms returning, and there were notable improvements in growth rates, protein, and calorie intakes after starting HMHMF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human-Based Human Milk Fortifier as Rescue Therapy in Very Low Birth Weight Infants Demonstrating Intolerance to Bovine-Based Human Milk Fortifier. Sandhu, A., Fast, S., Bonnar, K., et al.[2018]

A study involving 127 preterm infants found that using a human milk-derived fortifier did not significantly reduce the risk of necrotizing enterocolitis compared to a bovine milk-derived fortifier, indicating similar safety profiles for both types of fortifiers.

The evidence from this single trial suggests that human milk-derived fortifiers do not improve growth, reduce feeding intolerance, or decrease mortality in preterm infants fed breast milk, highlighting the need for more comprehensive studies to assess their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human milk-derived fortifier versus bovine milk-derived fortifier for prevention of mortality and morbidity in preterm neonates. Premkumar, MH., Pammi, M., Suresh, G.[2021]

In a study of 144 preterm infants, those receiving a new powdered human milk fortifier (SF) showed significantly greater weight gain and length growth compared to those receiving a commercial fortifier (CF), with weight gain differences of 2.6 g/kg/day in the intent-to-treat analysis.

The new fortifier (SF) was well-tolerated and led to faster growth milestones, with infants reaching 1800 g weight at an earlier time (SDAY 18) compared to those on the CF (SDAY 25), indicating its potential as a superior nutritional supplement for preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced growth of preterm infants fed a new powdered human milk fortifier: A randomized, controlled trial. Reis, BB., Hall, RT., Schanler, RJ., et al.[2019]

Liquid human milk fortifiers (HMFs) made from whey or casein hydrolysate may promote better growth in very low-birth-weight (VLBW) infants compared to powder HMFs, with evidence suggesting greater linear growth and weight gain.

However, there is insufficient evidence to conclude that these HMFs impact the incidence of necrotizing enterocolitis (NEC) or late-onset sepsis, highlighting the need for more robust studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of liquid human milk fortifiers: A systematic review and meta-analysis. Bridges, KM., Newkirk, M., Byham-Gray, L., et al.[2021]

Fortifying human milk is essential for very low birth weight (VLBW) infants to ensure they receive the necessary nutrients for adequate growth and development, which is crucial for their brain development and long-term neurodevelopmental outcomes.

The article discusses the complexities of fortification decisions, including the differences between mother's milk and donor milk, types of fortifiers, optimal timing for fortification, and when to stop fortification, highlighting the need for careful management in neonatal care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dilemmas in human milk fortification. Hair, AB., Scottoline, B., Good, M.[2023]

Human milk from mothers who deliver prematurely is richer in protein and bioactive molecules, making it crucial for the growth and development of premature infants.

Fortifying human milk is necessary for these infants to achieve adequate growth, and using mother's own milk can significantly reduce the risks of serious conditions like necrotizing enterocolitis and late-onset sepsis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human milk for the premature infant. Underwood, MA.[2022]

Supplementing human milk with multicomponent fortifiers in premature infants leads to short-term improvements in weight gain and growth measurements, such as linear and head growth.

There is currently insufficient evidence to determine long-term benefits or adverse effects of these fortifiers, although they do not appear to cause significant harm in the short term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicomponent fortified human milk for promoting growth in preterm infants. Kuschel, CA., Harding, JE.[2020]

Citations

1. prolacta.com prolacta.com/en/

Human Milk Fortifier: Improving Health for Infants – Prolacta Surgifort fortifier is the first and only 100% human milk-based fortifier intended for and approved by the US FDA for term infants with gastroschisis.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38545091/

Effect of human milk-based fortification in extremely ... Our results do not support routine supplementation with HMBF as a nutritional strategy to prevent NEC, sepsis, or death in extremely preterm infants ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2589537023005527

Articles Effect of human milk-based fortification in extremely ... Mortality and severe morbidity remain high in extremely preterm infants. Human milk-based nutrient fortifiers may prevent serious complications and death. We ...

4. prolacta.com prolacta.com/en/news/Galis_Study_2024/

Human milk-based fortifiers cut mortality rate by 50% in ... “The data associates bovine (cow) milk-based fortifiers with a potentially increased risk of death in preterm infants, which makes a reversal ...

5. prolacta.com prolacta.com/en/parents/

Human Milk-Based Fortifiers Matter Human milk–based fortifiers matter to critically ill and premature infants. Premature infants need additional calories and protein that are vital to their ...

6. hcp.meadjohnson.com hcp.meadjohnson.com/s/product/a4R4J000000PpQRUA0/enfamil-liquid-human-milk-fortifier-high-protein

Enfamil® Liquid Human Milk Fortifier High Protein Enfamil Liquid Human Milk Fortifier High Protein is added to expressed breast milk for feeding premature and low-birth-weight infants.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10965410/

Effect of human milk-based fortification in extremely preterm ... The study found that human milk-based fortifier did not reduce the incidence of NEC, sepsis, or death in preterm infants compared to bovine milk-based ...

8. prolacta.com prolacta.com/en/parents/your-babys-nutritional-needs/

Your baby's nutrition needs The term “Human Milk Fortifier (HMF)” is a generic product name for a nutritional supplement that hospitals can add to mother's own milk or donor breastmilk.

9. publications.aap.org publications.aap.org/pediatrics/article/152/3/e2023061603/193280/Early-Human-Milk-Fortification-in-Infants-Born

Early Human Milk Fortification in Infants Born Extremely ... This trial indicates that early human milk fortification increases length gain velocity and reduces declines in head circumference z scores from birth to term ...

10. aspenjournals.onlinelibrary.wiley.com aspenjournals.onlinelibrary.wiley.com/doi/10.1002/jpen.2558

Osmolality of fortified donor human milk: An experimental study Commercial human milk fortifiers (HMFs) appear to be well tolerated, support preterm infant growth, and may increase bone mineralization and ...