Individualized Human Milk Fortification for Very Low Birth Weight Infants

Recruiting at 19 trial locations

Overseen By Sharon Unger, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: The Hospital for Sick Children

Disqualifiers: Congenital anomalies, Chromosomal anomalies, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 weeks gestational age or hospital discharge

615 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 BUN adjustable fortification for very low birth weight infants?

Research shows that using adjustable protein fortification based on blood urea nitrogen (BUN) levels can help improve growth in preterm infants by ensuring they receive the right amount of protein. This individualized approach aims to meet the specific nutritional needs of each infant, potentially leading to better growth and health outcomes. ^{1 2 3 4 5}

Is individualized human milk fortification safe for very low birth weight infants?

Research indicates that individualized human milk fortification, including methods like targeted and adjustable fortification, is generally safe for preterm infants. Studies have shown no significant clinical complications and no adverse changes in important blood markers, suggesting it is a safe option for supporting growth in very low birth weight infants. ^{1 2 4 6 7}

What makes BUN adjustable fortification unique for very low birth weight infants?

BUN adjustable fortification is unique because it uses blood urea nitrogen levels to tailor the protein content in human milk specifically for each infant, ensuring they receive the right amount of nutrients for optimal growth. This individualized approach addresses the variability in human milk composition, which standard fortification methods cannot accommodate. ^{1 2 5 8 9}

What is the purpose of this trial?

Very low birth weight infants have increased nutritional needs. Extra nutrients are added to their human milk feeds to help improve their nutritional status, growth and neurodevelopment. Standard fortification of human milk is routine in most neonatal units in North America, but despite the added nutrients, infants are often discharged from hospitals with poor growth, and their neurodevelopment remains suboptimal. Two individualized fortification methods, target and BUN adjustable, have been proposed to improve the nutrient supply to infants. However, there is currently insufficient evidence to support the implementation of individualized fortification or one method over the other. Therefore, this study will randomly assign very low birth weight infants to receive feeds fortified according to standard, target or BUN adjustable fortification methods until the end of the feeding intervention. Feedings will be prepared in milk preparation rooms to ensure caregivers and outcomes assessor remain blinded to feeding allocation. Growth, morbidities, and nutrient intakes will be determined throughout hospitalization and skinfolds assessed at 36 weeks. At 4 months CA, growth and body composition will be determined by air displacement plethysmography on a subset of infants. Neurodevelopment will be assessed using the Bayley Scales of Infant and Toddler Development, at 18-24 months CA.

Research Team

Deborah O'Connor, PhD RD

Principal Investigator

The Hospital for Sick Children

Sharon Unger, MD

Principal Investigator

Sinai Health System

Eligibility Criteria

This trial is for infants born weighing ≤ 1250 g. They must have parental consent and can use donor milk if needed. Infants who might transfer to a non-participating NICU, received fortifiers or formula before the study, are over 21 days old at start, in another nutrition study, or have growth-affecting anomalies cannot join.

Inclusion Criteria

Parental/guardian consent to participate

Consent for the use of pasteurized donor milk if mother's milk is not available

My baby was born weighing 1250 grams or less.

Exclusion Criteria

Reasonable potential that the infant will be transferred to a NICU where the study protocol will not be continued

Infant received fortifier or formula before Study Day 1

Study Day 1 to occur after day 21 of life

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Infants receive feeds fortified according to standard, target, or BUN adjustable methods until 36 weeks gestational age or hospital discharge

Up to 36 weeks gestational age or hospital discharge

Follow-up

Growth and body composition are assessed at 4 months corrected age, and neurodevelopment is assessed at 18-24 months corrected age

18-24 months corrected age

Treatment Details

Interventions

• BUN adjustable fortification
• Standard fortification
• Target fortification

Trial Overview The trial tests how very low birth weight infants grow when their human milk is fortified using three different methods: standard fortification, target fortification based on desired nutrient levels, and BUN adjustable fortification that adapts to the infant's current nutritional status.

Participant Groups

Group I: Target fortification Experimental Treatment 1 Intervention

Group II: BUN adjustable fortification Experimental Treatment 1 Intervention

Group III: Standard fortification Active Control 1 Intervention

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Findings from Research

In a study of 58 preterm infants born at or before 32 weeks of gestation, those receiving adjustable protein fortification showed significantly higher daily protein intake (4 g/kg/day) compared to the control group (2.78 g/kg/day), leading to improved growth outcomes.

The intervention group experienced significantly greater growth velocities in length and head circumference, as well as higher daily growth indexes for weight, length, and head circumference, indicating that tailored protein supplementation can enhance growth in very low birth weight infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An intention to achieve better postnatal in-hospital-growth for preterm infants: adjustable protein fortification of human milk. Alan, S., Atasay, B., Cakir, U., et al.[2022]

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]

The adjustable fortification (ADJ) regimen significantly improved growth parameters, such as daily weight gain and head circumference, in premature infants compared to standard fortification, with 119 infants in the ADJ group showing better results at 40 weeks.

While 63% of infants in the ADJ group required additional protein supplementation (up to 1.6 g/day) to reach target blood urea nitrogen (BUN) levels, this increased protein intake was found to be safe and beneficial for their growth in the NICU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What should be the protein target for adjustable Human Milk fortification in premature infants? Dorum, BA., Ozkan, H., Cakir, SC., et al.[2022]

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]

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]

Fortifying human milk with post discharge formula (PDF) significantly improved growth parameters in preterm very low birth weight (VLBW) infants, with higher weight gain (16.8 g/kg/day vs. 13.78 g/kg/day) and increased length and head circumference compared to controls.

The use of PDF also reduced the duration of hospital stays for these infants (22.76 days vs. 28.52 days), while showing no significant adverse effects on biochemical markers or clinical complications, suggesting it is a safe and effective option for milk fortification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post Discharge Formula Fortification of Maternal Human Milk of Very Low Birth Weight Preterm Infants: An Introduction of a Feeding Protocol in a University Hospital. El Sakka, A., El Shimi, MS., Salama, K., et al.[2022]

In a study of very low-birth-weight (VLBW) preterm infants, individualized protein fortification using a targeted method resulted in significantly higher daily protein intake and better growth outcomes compared to an adjustable fortification method.

The targeted fortification group showed greater daily weight gain and head circumference increase, indicating that this method is more effective for supporting the growth of VLBW infants in the early weeks of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Targeted Versus Adjustable Protein Fortification of Breast Milk on Early Growth in Very Low-Birth-Weight Preterm Infants: A Randomized Clinical Trial. Bulut, O., Coban, A., Uzunhan, O., et al.[2020]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

An intention to achieve better postnatal in-hospital-growth for preterm infants: adjustable protein fortification of human milk. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

3. Pakistan pubmed.ncbi.nlm.nih.gov

What should be the protein target for adjustable Human Milk fortification in premature infants? [2022]

4. 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]

5. 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]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Post Discharge Formula Fortification of Maternal Human Milk of Very Low Birth Weight Preterm Infants: An Introduction of a Feeding Protocol in a University Hospital. [2022]

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

Effects of Targeted Versus Adjustable Protein Fortification of Breast Milk on Early Growth in Very Low-Birth-Weight Preterm Infants: A Randomized Clinical Trial. [2020]

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

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