Fortified Donor Breast Milk for Preterm Infants

Overseen By Jenny Taylor, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Columbia University

Disqualifiers: Congenital heart disease, GI diagnoses, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 11 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a randomized controlled trial comparing standard fortification of donor breast milk to targeted fortification of donor breast milk in preterm infants. The purpose of the study is to determine if there is a benefit to target fortifying donor breast milk in the preterm population. The investigators hypothesize that infants receiving targeted fortification of donor breast milk will have improved growth compared to infants receiving standard fortification of donor breast milk.

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 Fortified Donor Breast Milk for Preterm Infants?

Research shows that fortifying human milk with additional nutrients, like protein, calcium, and phosphate, helps preterm infants grow better and reduces the risk of health issues. Studies have found that liquid human milk fortifiers improve growth and feeding tolerance in preterm infants. ^{1 2 3 4 5}

Is fortified donor breast milk safe for preterm infants?

Research shows that fortified donor breast milk is generally safe for preterm infants, with studies focusing on growth, tolerance, and safety. Some studies have noted issues like metabolic acidosis (a condition where the body produces too much acid) with certain fortifiers, but overall, fortified milk supports better growth and bone health in preterm infants. ^{1 2 5 6 7}

How does the treatment of fortified donor breast milk for preterm infants differ from other treatments?

This treatment is unique because it combines multiple fortifiers to enhance the nutritional content of donor breast milk, specifically tailored for preterm infants, aiming to improve growth and bone mineralization. Unlike standard fortification, this approach uses a combination of carbohydrates, lipids, and proteins to meet the high nutritional needs of preterm infants. ^{1 5 7 8 9}

Research Team

Marianne Garland, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for premature infants born at or before 30 weeks and weighing less than or equal to 1500 grams. It's not for those who are very small for their gestational age, have certain heart or gastrointestinal conditions, severe brain hemorrhage, haven't started fortified feeds by 3 weeks old, have necrotizing enterocolitis, or early onset sepsis.

Inclusion Criteria

My birth weight was 1500 grams or less.

My baby was born at or before 30 weeks of pregnancy.

Exclusion Criteria

I have been diagnosed with necrotizing enterocolitis.

Parents do not consent to donor milk

I do not have heart, GI conditions, or major birth defects affecting growth.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either standard or targeted fortification of donor breast milk until they reach 34 weeks corrected gestational age

Up to 11 weeks

Follow-up

Participants are monitored for growth metrics such as weight, length, and head circumference

Up to 11 weeks

Long-term follow-up

Participants are monitored for secondary outcomes such as NICU length of stay, mortality rate, and incidence of conditions like NEC and retinopathy of prematurity

Up to 1 year

Treatment Details

Interventions

• Medica Nutrition SolCarb
• Nestle Microlipid
• Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid
• Similac Liquid Protein Fortifier

Trial Overview The study tests if adding extra nutrients (targeted fortification) to donor breast milk helps preterm babies grow better compared to standard nutrient addition. Babies will be randomly assigned to receive either the standard or targeted fortification.

Participant Groups

Group I: Experimental Experimental Treatment 5 Interventions

Targeted fortification of breast milk

Group II: Control Experimental Treatment 5 Interventions

Standard fortification of breast milk

Medica Nutrition SolCarb is already approved in European Union, United States for the following indications:

Approved in European Union as SolCarb for:

• Nutritional support for preterm infants

Approved in United States as SolCarb for:

• Nutritional support for preterm infants

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

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 147 preterm infants, the new concentrated liquid human milk fortifier (LE-HMF) showed noninferior weight gain compared to the standard powdered fortifier (PI-HMF), with both groups achieving excellent weight gain and tolerance.

Infants fed LE-HMF demonstrated significantly greater weight and linear growth over time compared to those fed PI-HMF, indicating that LE-HMF may be a more effective option for promoting growth in preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth and Tolerance of Preterm Infants Fed a New Extensively Hydrolyzed Liquid Human Milk Fortifier. Kim, JH., Chan, G., Schanler, R., et al.[2018]

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]

Human milk is the best nutrition for both term and preterm infants, but very low birth weight (VLBW) infants often require additional fortification to meet their nutritional needs, particularly for protein, calcium, and phosphate.

The European Milk Bank Association recommends individualized fortification methods, such as Adjustable and Targeted Fortification, to better meet the specific nutrient requirements of VLBW infants, as standard fortification may not provide sufficient protein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fortification of Human Milk for Preterm Infants: Update and Recommendations of the European Milk Bank Association (EMBA) Working Group on Human Milk Fortification. Arslanoglu, S., Boquien, CY., King, C., et al.[2020]

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]

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]

Fortifying preterm human milk with protein, calcium, and phosphorus significantly improved bone mineral content and growth rates in low birth weight infants compared to unfortified human milk.

The fortified human milk provided growth rates comparable to a special formula for low birth weight infants, although all groups still fell below the 50th percentile for weight at discharge, indicating a need for further nutritional support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved bone mineralization and growth in premature infants fed fortified own mother's milk. Greer, FR., McCormick, A.[2019]

In a trial involving 39 preterm infants, tailored fortification of human milk did not significantly improve weight gain compared to standard fortification, with average gains of 27.01 g/d and 25.84 g/d respectively.

The study highlighted challenges in implementing targeted fortification in neonatal intensive care units, suggesting that while it is a promising approach, its feasibility may be limited in practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Targeted vs. Standard Fortification of Breast Milk on Growth and Development of Preterm Infants (≤32 Weeks): Results from an Interrupted Randomized Controlled Trial. Seliga-Siwecka, J., Fiałkowska, J., Chmielewska, A.[2023]

In a study examining the stability of vitamins and minerals in the Similac Special Care formula for premature infants, significant reductions in calcium (44-54%), iron (23-34%), and zinc (18-32%) were observed after continuous infusion, indicating that infants may not receive the expected amounts of these nutrients.

In contrast, another formula, Similac 24LBW, showed stable concentrations of all vitamins and minerals tested, suggesting that it may be a more reliable option for ensuring nutrient delivery in premature infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability of vitamin and mineral concentrations of a low-birth-weight infant formula during continuous enteral feeding. Antonson, DL., Smith, JL., Nelson, RD., et al.[2019]

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

Growth and Tolerance of Preterm Infants Fed a New Extensively Hydrolyzed Liquid Human Milk Fortifier. [2018]

3. 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]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Fortification of Human Milk for Preterm Infants: Update and Recommendations of the European Milk Bank Association (EMBA) Working Group on Human Milk Fortification. [2020]

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

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

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

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

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

Improved bone mineralization and growth in premature infants fed fortified own mother's milk. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Targeted vs. Standard Fortification of Breast Milk on Growth and Development of Preterm Infants (≤32 Weeks): Results from an Interrupted Randomized Controlled Trial. [2023]

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

Stability of vitamin and mineral concentrations of a low-birth-weight infant formula during continuous enteral feeding. [2019]