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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two types of milk fortifiers for aiding the growth of preterm infants: one derived from human milk and the other from bovine (cow) milk. The researchers aim to determine which fortifier better meets the nutritional needs of very low birth weight (VLBW) infants, who require extra nutrients for optimal growth. Infants born weighing between 400 and 1250 grams, at or before 32 weeks, and able to receive human milk within 72 hours after birth may be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to research that could enhance nutritional care for preterm infants.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fortifiers made from human milk are safe and generally well-tolerated. One study found that a new type of human milk fortifier aids growth in preterm infants and is safe to use. Another study discovered that these fortifiers reduced the death rate in preterm infants by half, resulting in fewer fatalities.

For fortifiers made from cow's milk, studies indicate they are also safe and well-tolerated in very low birth weight infants. However, they did not demonstrate any clear advantage in promoting growth compared to human milk fortifiers. Both types of fortifiers are considered safe, but human milk fortifiers may offer additional benefits, such as reducing the risk of death. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about human milk-derived human milk fortifiers (HMF) for preterm infant growth because they offer a more natural option compared to the current standard, which uses bovine milk-derived products. Human milk-derived HMF is thought to be more compatible with a preterm infant's digestive system, potentially reducing the risk of feeding intolerance and other complications associated with bovine-based fortifiers. This approach could support better growth and development in these vulnerable infants by providing nutrients that are closer to those found in human breast milk.

What evidence suggests that this trial's treatments could be effective for preterm infant growth?

This trial will compare the effects of human milk-derived fortifiers and bovine milk-derived fortifiers on preterm infant growth. Research has shown that fortifiers made from human milk can lead to better growth in premature babies, helping them grow taller and gain healthy body mass, which is crucial for brain development in very small infants. Participants in this trial may receive human milk-derived fortifiers, which some studies suggest lower the risk of a serious gut disease called NEC, although they might not promote as much weight gain as cow's milk fortifiers. Alternatively, participants may receive bovine milk-derived fortifiers, which are safe and easy for babies to digest but do not show the same growth benefits as human milk fortifiers. Both types of fortifiers are designed to meet the nutritional needs of premature babies, offering different benefits. ^{1 6 7 8 9}

Who Is on the Research Team?

Belal M Alshaikh, MD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7490161/

Human Milk–Derived Fortifiers Compared with Bovine Milk ...

Fortification of milk in preterm infants with HMF compared with BMF decreased the risk of NEC but was associated with lower weight gain.

2.

nature.com

nature.com/articles/s41372-024-01998-0

Immediate fortification of human milk with a bovine ...

Immediate fortification of enteral feedings with a bovine milk-derived HMF appears safe and well-tolerated although no clear growth benefit could be ...

3.

mdpi.com

mdpi.com/2072-6643/16/6/910

Association of Fortification with Human Milk versus Bovine ...

This meta-analysis assessed short-term outcomes after using human milk-derived fortifiers (HMFs) compared with bovine milk fortifiers (BMFs) in preterm infants.

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/32277813/

Human Milk-Derived Fortifiers Compared with Bovine ...

Fortification of milk in preterm infants with HMF compared with BMF decreased the risk of NEC but was associated with lower weight gain.

5.

ijpediatrics.com

ijpediatrics.com/index.php/ijcp/article/download/6354/3885/28884

Efficacy of exclusive human milk diet in preterm infants ...

The mean weight gain was 25.5±5.5 g/day and the mean growth velocity was 17.8±3.4 g/kg/day. Feeding intolerance was observed in 4 infants (16%), ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6837687/

Human milk‐derived fortifier versus bovine ... - PubMed Central

Human milk-derived fortifier did not reduce necrotizing enterocolitis, improve growth, or decrease death in preterm infants compared to bovine milk-derived ...

7.

frontiersin.org

frontiersin.org/journals/pediatrics/articles/10.3389/fped.2024.1354683/full

Human milk-derived versus bovine milk-derived fortifier ...

This study aims to compare HMDF and BMDF effects on growth parameters and serum 25-hydroxy vitamin D (25OHD) levels in preterm very low birth weight (VLBW) ...

8.

thelancet.com

thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00552-7/fulltext

Effect of human milk-based fortification in extremely ...

Human milk-based nutrient fortifiers may prevent serious complications and death. We aimed to investigate whether supplementation with human milk-based ...

9.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38724605/

Immediate fortification of human milk with a bovine ... - PubMed

The study found immediate fortification of human milk with a bovine milk-derived fortifier appears safe and well-tolerated, but no clear growth benefit was ...