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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two methods to enhance the nutrients in breast milk for premature babies in the NICU. One group receives milk fortified as usual, while the other group receives milk adjusted based on specific needs measured by a quick test, known as individually targeted fortification. The researchers aim to assess how these methods affect babies' growth, brain development, and progress over time. Babies born between 24 and 30 weeks, currently in the NICU at Brigham and Women's Hospital, with mothers providing breast milk, may be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to research that could improve nutrition for premature infants.

Will I have to stop taking my current medications?

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

What prior data suggests that these methods of milk fortification are safe for preterm infants?

Research has shown that adding extra nutrients to breast milk, especially for babies born early, is generally safe and beneficial. Studies have found that adjusting the milk to meet specific needs helps preterm babies grow and develop better than using a standard approach.

Evidence suggests that human milk-based fortifiers, which enhance the nutrition in breast milk, can help prevent serious health issues in very early-born babies. Reports of negative effects from these fortifiers are rare, and they are generally well-tolerated, meaning babies usually do not have adverse reactions to them.

Overall, for those considering participation in a study using personalized fortification, current evidence indicates it is a safe and possibly more effective way to support the growth and development of preterm babies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about individually targeted fortification for premature infants because it personalizes nutrition to meet each infant's specific needs. Unlike standard fortification methods, which add a fixed amount of nutrients, this approach adjusts protein and calorie levels to ensure optimal growth and development. By tailoring the fortification to achieve precise nutritional targets, it has the potential to prevent growth faltering more effectively than the one-size-fits-all standard of care. This could lead to better health outcomes for premature infants by providing them with the exact nutrition they need to thrive.

What evidence suggests that individually targeted fortification is effective for premature infants?

Research has shown that customizing the nutrients in breast milk for each preterm baby, as done in the individually targeted fortification arm of this trial, better meets their needs than standard methods. Studies have found that this personalized approach helps these babies grow better in the early stages, which is vital for their development. By adjusting nutrients specifically for each baby, this method may prevent serious health issues common in very premature infants. Evidence suggests that using this tailored fortification in breast milk leads to better growth and development outcomes for these vulnerable babies during a critical time. ^{1 2 3 5 6}

Who Is on the Research Team?

Mandy B Belfort, MD, MPH

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33836708/

Targeting human milk fortification to improve very preterm ... We hypothesize that individually targeted human milk fortification is more effective in meeting macronutrient requirements than the current standard of care.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6439523/

Fortification of Human Milk for Preterm Infants: Update and ... EMBA encourages the use of “Individualized Fortification” to optimize nutrient intake. “Adjustable Fortification” and “Targeted Fortification” are 2 methods of ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2589537023005527

Articles Effect of human milk-based fortification in extremely ... Mortality and severe morbidity remain high in extremely preterm infants. Human milk-based nutrient fortifiers may prevent serious complications and death.

4. frontiersin.org frontiersin.org/journals/pediatrics/articles/10.3389/fped.2024.1466528/full

Narrative review of methodological advances in human ... Studies have demonstrated that either adjustable or targeted fortification is more effective than SF in promoting early physical growth in ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04294368

Targeted Fortification of Donor Breast Milk in Preterm Infants This study is a randomized controlled trial comparing standard fortification of donor breast milk to targeted fortification of donor breast milk in preterm ...

6. mdpi.com mdpi.com/2072-6643/17/11/1764

Individualized Target Fortification of Breast Milk with ... This study aims to evaluate the effects of TFO compared to SF on growth, body composition, and neurological outcomes at 18 months corrected age.