Targeted Milk Fortification for Premature Infants

Overseen By Tina Steele, RN

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Disqualifiers: Congenital anomaly, Growth restriction, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

130 Participants Needed

Trial Summary

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 Targeted Milk Fortification for Premature Infants?

Research suggests that targeted fortification of human milk, which adjusts nutrients based on individual needs, may help improve growth in preterm infants by addressing the variability in milk composition. However, a study found no significant difference in weight gain between targeted and standard fortification, indicating that while promising, the approach may have limitations in practice. ^{1 2 3 4 5}

Is targeted milk fortification safe for premature infants?

Research on targeted milk fortification for premature infants suggests it is generally safe, but data on long-term safety is limited. Studies have focused on improving growth and nutrition, with some indicating potential benefits, but more research is needed to fully understand safety over extended periods. ^{1 2 4 6 7}

How is targeted milk fortification different from other treatments for premature infants?

Targeted milk fortification is unique because it customizes the nutrient content of human milk based on its actual composition, using point-of-care analysis, rather than assuming standard nutrient levels. This approach aims to better meet the specific nutritional needs of premature infants, potentially improving their growth and development compared to standard fixed-dose fortification methods. ^{1 2 5 6 8}

What is the purpose of this trial?

This study is a randomized trial comparing 2 methods of human milk fortification for preterm infants in the neonatal intensive care unit (NICU). All participating infants will receive a human milk diet comprising maternal and/or donor milk plus multi-component and modular fortifiers. In one group (control), the milk will be fortified according to routine standard of care. In the other group (intervention), the fortification will be individually targeted based on the results of point-of-care human milk analysis. Outcomes include physical growth in the NICU and after discharge, brain structure by magnetic resonance imaging at term equivalent age, and neurodevelopment at 2 years.

Research Team

Mandy B Belfort, MD, MPH

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for preterm infants in Brigham and Women's Hospital NICU, born between 24 to nearly 31 weeks of gestation, less than 21 days old, with mothers providing breast milk. It excludes those with major birth defects, severe growth issues, certain gastrointestinal conditions, multiples beyond twins, life-threatening health status or expected transfer before reaching 36 weeks postmenstrual age.

Inclusion Criteria

Mother providing breast milk

I am less than 21 days old.

My pregnancy is between 24 and 30 weeks.

Exclusion Criteria

I have serious kidney or liver problems.

Major congenital anomaly

Parents do not consent to use of pasteurized donor human milk

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

Diet Intervention

Participants receive either standard or individually targeted human milk fortification until 36 weeks' postmenstrual age or hospital discharge

Up to 15 weeks

Regular monitoring in NICU

Follow-up

Participants are monitored for growth and neurodevelopmental outcomes at term equivalent age and at 2 years corrected age

2 years

MRI at term equivalent age, developmental assessments at 2 years

Treatment Details

Interventions

• Individually targeted fortification

Trial Overview The study compares two human milk fortification methods for premature babies: standard care versus targeted fortification based on real-time milk analysis. The goal is to see which method better supports physical growth and brain development up to the age of two years.

Participant Groups

Group I: Individually targeted fortification Experimental Treatment 1 Intervention

Standard of care fortification plus extra protein and/or calories to ensure that "base" milk has protein 1 g/dL and calories 67/dL.

Group II: Standard fortification Active Control 1 Intervention

Standard of care fortification with multicomponent human milk fortifier (24 kcal/oz) and liquid protein (0.27 g/dL); additional protein and/or calories added only for growth faltering.

Individually targeted fortification is already approved in European Union, United States for the following indications:

Approved in European Union as Individually Targeted Fortification for:

• Preterm infant nutrition
• Neonatal intensive care unit (NICU) support

Approved in United States as Individually Targeted Fortification for:

• Preterm infant nutrition
• NICU support
• Growth and brain development enhancement

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

Human milk is essential for very preterm infants, providing significant short-term and long-term health benefits, but often requires fortification to meet their nutritional needs during hospitalization.

Individually targeted fortification, using point-of-care analysis of human milk composition, shows promise in addressing nutrient delivery gaps and improving growth outcomes for these infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Milk Fortification for Very Preterm Infants: Toward Optimal Nutrient Delivery, Neonatal Intensive Care Unit Growth, and Long-Term Outcomes. Talebiyan, S., Belfort, MB.[2023]

A study involving 32 healthy preterm infants showed that both bovine whey protein and ultrafiltrated human milk protein fortifiers were well tolerated and resulted in similar growth outcomes, indicating their efficacy in nutritional management.

The individualized fortification approach, based on protein content analysis of human milk, allows for tailored feeding strategies that can achieve equivalent protein intake and growth results in preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized protein fortification of human milk for preterm infants: comparison of ultrafiltrated human milk protein and a bovine whey fortifier. Polberger, S., Räihä, NC., Juvonen, P., et al.[2022]

In a study involving 120 preterm neonates, individualized plus optimized nutrition did not lead to better weight gain or linear growth compared to optimized nutrition alone, with similar results in both groups.

Both groups showed equivalent weight-gain velocity and linear growth rates, indicating that the additional individualized approach may not provide significant benefits over standard optimized nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing individual nutrition in preterm very low birth weight infants: double-blinded randomized controlled trial. Brion, LP., Rosenfeld, CR., Heyne, R., et al.[2021]

The EMBA Working Group emphasizes the importance of using metabolic markers to tailor protein intake for preterm infants, which can enhance their nutritional support.

They clarify two methods of individualized human milk fortification: Adjustable and Targeted, each with its own advantages and disadvantages, highlighting the need for careful consideration in their application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letter to the editor: clarifying some aspects and the terminology of individualized human milk fortification. Arslanoglu, S., King, C., Boquien, CY., et al.[2020]

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]

Targeted fortification of human milk significantly improved growth rates in very low birth weight preterm infants, with weekly weight gain averaging 205.5 g compared to 155 g in those receiving standard fortification.

The study found no gastrointestinal or metabolic intolerance in infants receiving targeted fortification, indicating it is a safe method for enhancing nutrition in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is targeted fortification of human breast milk an optimal nutrition strategy for preterm infants? An interventional study. Morlacchi, L., Mallardi, D., Giannì, ML., et al.[2022]

A randomized controlled trial is being conducted with 130 very preterm infants to test whether individually targeted human milk fortification is more effective than standard fortification in meeting their macronutrient needs.

The study will assess key outcomes such as body length, lean body mass, brain size, and cognitive development at various stages, providing valuable insights into the benefits of personalized nutrition for preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting human milk fortification to improve very preterm infant growth and brain development: study protocol for Nourish, a single-center randomized, controlled clinical trial. Belfort, MB., Woodward, LJ., Cherkerzian, S., et al.[2021]

Targeted fortification of human milk, which involves analyzing its actual macronutrient composition, is crucial for the nutritional care of very low birthweight infants, ensuring they receive the necessary nutrients for growth.

The use of human milk analyzers in clinical settings allows for precise measurement of protein, fat, lactose, and energy in human milk, but there are still barriers to implementing this practice widely and research gaps that need to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted fortification with human milk analysis: An opportunity for innovation. Merlino Barr, S., Groh-Wargo, S.[2022]

References

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

Human Milk Fortification for Very Preterm Infants: Toward Optimal Nutrient Delivery, Neonatal Intensive Care Unit Growth, and Long-Term Outcomes. [2023]

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

Individualized protein fortification of human milk for preterm infants: comparison of ultrafiltrated human milk protein and a bovine whey fortifier. [2022]

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

Optimizing individual nutrition in preterm very low birth weight infants: double-blinded randomized controlled trial. [2021]

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

Letter to the editor: clarifying some aspects and the terminology of individualized human milk fortification. [2020]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

Is targeted fortification of human breast milk an optimal nutrition strategy for preterm infants? An interventional study. [2022]

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

Targeting human milk fortification to improve very preterm infant growth and brain development: study protocol for Nourish, a single-center randomized, controlled clinical trial. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Targeted fortification with human milk analysis: An opportunity for innovation. [2022]