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

Trial Summary

What is the purpose of this trial?

The aim of the project is to study the effects of fortification (using a Human Milk Donor Fortifier) of an exclusive preterm human milk diet on outcome of extremely preterm neonates, born at less or equal to 27 weeks.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment Human Milk Fortification for Premature Infants?

Research shows that fortifying human milk helps premature infants grow better and reduces risks of serious conditions like necrotizing enterocolitis (a severe intestinal disease) and late-onset sepsis (a blood infection). Liquid human milk fortifiers, like those from Prolacta Bioscience, are designed to provide essential nutrients safely and effectively. ^{1 2 3 4 5}

Is human milk fortifier safe for premature infants?

Research indicates that human milk fortifiers, especially those based on human milk, are generally safe for premature infants and can help meet their nutritional needs. Some studies suggest that human milk-based fortifiers may be better tolerated than those based on cow's milk, which have been associated with issues like feeding intolerance and metabolic acidosis (a condition where the body produces too much acid). ^{1 6 7 8 9}

How is Human Milk Donor Fortifier different from other treatments for premature infants?

Human Milk Donor Fortifier is unique because it is an ultraconcentrated liquid fortifier designed to provide optimal nutrients for premature infants using human breast milk, unlike traditional bovine milk-based fortifiers. This allows for an exclusive human milk diet, which can reduce the risk of certain health issues in very low birth weight infants. ^{1 3 7 10 11}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A new liquid human milk fortifier and linear growth in preterm infants. [2012]

2. United States pubmed.ncbi.nlm.nih.gov

Enhanced growth of preterm infants fed a new powdered human milk fortifier: A randomized, controlled trial. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Human milk for the premature infant. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Human milk-derived fortifier versus bovine milk-derived fortifier for prevention of mortality and morbidity in preterm neonates. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of liquid human milk fortifiers: A systematic review and meta-analysis. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

A randomized, controlled evaluation of two commercially available human breast milk fortifiers in healthy preterm neonates. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Implementing an exclusive human milk diet for preterm infants: real-world experience in diverse NICUs. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Association of metabolic acidosis with bovine milk-based human milk fortifiers. [2021]

9. United States 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. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Multicomponent fortified human milk for promoting growth in preterm infants. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Dilemmas in human milk fortification. [2023]