Human vs. Bovine Milk-Based Fortifiers for Preterm Infant Growth

Overseen By Belal Alshaikh, MD, MSc

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Disqualifiers: Congenital abnormalities, Maternal substance abuse, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

42 Participants Needed

Trial Summary

What is the purpose of this trial?

Human Milk alone is unable to meet the high nutritional requirements of preterm infants. The American Academy of Pediatrics recommends fortification of human milk as a standard practice in all very low birth weight (VLBW) infants. Multi-nutrient human milk fortifiers (HMFs) are designed to meet the macro and micro-nutrient needs of VLBW infants. HMFs differ by the origin of milk and by nutrient composition. Traditionally, bovine milk has been the main source of multi-nutrient HMFs.

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 bovine milk-derived HMF and human milk-derived HMF for preterm infant growth?

Research shows that liquid human milk fortifiers, which are similar to the treatments being studied, can help preterm infants grow better and tolerate feedings well. These fortifiers provide important nutrients that support the growth and health of very low-birth-weight infants. ^{1 2 3 4 5}

Is it safe to use human milk fortifiers for preterm infants?

Research indicates that liquid human milk fortifiers are generally safe for preterm infants, focusing on their growth and tolerance. Studies have evaluated their safety and effectiveness, particularly in providing necessary nutrients without causing harm. ^{3 5 6 7 8}

How does the human milk-derived HMF treatment differ from other treatments for preterm infant growth?

The human milk-derived HMF is unique because it is made from human protein sources, unlike most fortifiers that use bovine (cow) protein. This treatment is designed to better support the growth and nutritional needs of preterm infants by using ingredients that are more similar to human breast milk. ^{5 9 10 11 12}

Research Team

Belal M Alshaikh, MD

Principal Investigator

University of Calgary

Eligibility Criteria

This trial is for preterm infants with a birthweight of 400-1250g, born at or before 32 weeks, and classified as appropriate for their gestational age. They must have started enteral feeding with human milk within 72 hours of birth and are expected to continue for at least three weeks. Infants with HIV treatment, exposure to maternal substance abuse during pregnancy, major surgery, or diseases affecting growth cannot participate.

Inclusion Criteria

I started feeding my baby human milk within 3 days after birth.

You are considered to have a normal growth and development for your age.

My baby's birthweight was between 400 g and 1250 g.

Exclusion Criteria

My infant has undergone major surgery.

Maternal cocaine, alcohol, or opioid abuse during pregnancy

I or my infant is currently being treated for HIV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Preterm infants receive human milk fortified with either human milk-derived or bovine milk-derived fortifiers

3 weeks

Weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Weekly visits for head circumference and length measurements

Treatment Details

Interventions

• bovine milk-derived HMF
• Human milk-derived HMF

Trial Overview The study tests two types of fortifiers added to human milk: one derived from humans and the other from cows. These supplements aim to fulfill the nutritional needs of very low birth weight (VLBW) preterm infants who can't get enough nutrients from human milk alone.

Participant Groups

Group I: Bovine milk-derived HMF Experimental Treatment 1 Intervention

Current standard practice: Fortification with bovine milk-derived product

Group II: Human milk-derived HMF Active Control 1 Intervention

Fortification with human milk-derived product

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Findings from Research

In a study of 164 preterm infants, those fed a nonacidified liquid human milk fortifier experienced significantly greater weight gain in the first 15 days compared to those fed an acidified fortifier, despite both groups showing similar overall weight gain by day 29.

Infants receiving the acidified fortifier had higher rates of feeding intolerance, including more vomiting, gastric residuals, and metabolic acidosis, indicating potential safety concerns with this type of fortifier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Outcomes in Preterm Infants Fed a Nonacidified Liquid Human Milk Fortifier: A Prospective Randomized Clinical Trial. Schanler, RJ., Groh-Wargo, SL., Barrett-Reis, B., 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Human milk fortifier with high versus standard protein content for promoting growth of preterm infants: A meta-analysis. [2022]

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

Improved Outcomes in Preterm Infants Fed a Nonacidified Liquid Human Milk Fortifier: A Prospective Randomized Clinical Trial. [2019]

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

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

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

Nutrient enrichment of mother's milk and growth of very preterm infants after hospital discharge. [2011]

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

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

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

Feeding tolerance in premature infants fed fortified human milk. [2019]

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

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

8. New Zealand pubmed.ncbi.nlm.nih.gov

Relative cost-effectiveness of using a liquid human milk fortifier in preterm infants in the US. [2020]

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

Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. [2022]

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

Novel multinutrient human milk-based human milk fortifier promotes growth and tolerance in premature infants. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Growth, Feeding Tolerance and Metabolism in Extreme Preterm Infants under an Exclusive Human Milk Diet. [2020]

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

Growth and Nutritional Biomarkers of Preterm Infants Fed a New Powdered Human Milk Fortifier: A Randomized Trial. [2019]