Milk Fortification Methods for Preterm Infants' Growth

(FAT Trial)

Overseen By Adriana Reyes Loredo, MD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Must not be taking: Systemic steroids

Disqualifiers: Abnormal metabolic screen, Congenital anomalies, NEC, TORCH infections, AKI

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4-8 weeks

52 Participants Needed

Trial Summary

What is the purpose of this trial?

Research question: Do preterm infants born \<1250 g achieve better weight gain with targeted fortification compared with the adjustable fortification of human milk? Hypothesis: Targeted fortification of human milk results in better weight gain in infants with birth weight \<1250 gr when compared to the adjustable fortification. Study design: Open-label, pragmatic, parallel randomized controlled trial in appropriate for gestational age infants with birth weight \<1250 g.

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 Adjustable Human Milk Fortification for preterm infants' growth?

Research shows that adjustable fortification of human milk helps provide the right amount of protein, which is crucial for the growth and brain development of preterm infants. This method has been successfully used in neonatal intensive care units to ensure these infants receive adequate nutrition for proper growth. ^{1 2 3 4 5}

Is human milk fortification safe for preterm infants?

There is limited data on the safety of targeted human milk fortification, but concerns include high osmolality (concentration of particles in a solution), feed intolerance, and risk of necrotizing enterocolitis (a serious intestinal disease). However, fortification is a standard practice in developed countries to support growth in preterm infants. ^{1 6 7 8 9}

What makes the Adjustable and Targeted Human Milk Fortification treatment unique for preterm infants?

This treatment is unique because it involves individually adjusting the nutrient content of human milk based on point-of-care analysis to better meet the specific nutritional needs of each preterm infant, unlike standard fixed-dose fortification methods. ^{1 3 4 7 10}

Research Team

Belal M Alshaikh, MD

Principal Investigator

University of Calgary

Eligibility Criteria

This trial is for preterm infants born weighing less than 1250 grams and considered appropriate for their gestational age. They must be born at Foothills Medical Centre without major congenital anomalies, acute kidney injury, prior NEC, confirmed TORCH infections or abnormal newborn metabolic screen results.

Inclusion Criteria

Infants with birth weight <1250 g born at Foothills Medical Centre.

Appropriate for gestational age (AGA) (according to Fenton's Charts).

Exclusion Criteria

You were born with a major birth defect that requires ongoing medical treatment or surgery.

I have been diagnosed with a TORCH infection.

Abnormal Newborn Metabolic Screen

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Infants receive either adjustable or targeted human milk fortification based on randomization

4-8 weeks

Weekly visits for measurements and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Adjustable Human Milk Fortification
• Targeted Human Milk Fortification

Trial Overview The study is testing whether targeted fortification of human milk leads to better weight gain in preterm infants under 1250g compared to adjustable fortification. It's an open-label randomized controlled trial with two parallel groups.

Participant Groups

Group I: Targeted Human Milk Fortification Experimental Treatment 1 Intervention

Human milk fortification based on milk analysis

Group II: Adjustable Human Milk Fortification Active Control 1 Intervention

Human milk fortification based on blood urea levels

Adjustable Human Milk Fortification is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Human Milk Fortification for:

• Preterm infant nutrition
• Very low birth weight (VLBW) nutrition

Approved in United States as Human Milk Fortification for:

• Preterm infant nutrition
• VLBW nutrition

Approved in Canada as Human Milk Fortification for:

• Preterm infant nutrition
• VLBW nutrition

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

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]

Preterm infants typically receive less protein than needed when fed fortified human milk due to outdated assumptions, which can hinder their growth and neurocognitive development.

The Adjustable fortification regimen has been successfully implemented in several Italian NICUs, providing adequate protein intake and promoting appropriate growth in preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update of adjustable fortification regimen for preterm infants: a new protocol. Arslanoglu, S., Bertino, E., Coscia, A., 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]

In a study of 67 preterm infants receiving human milk with two types of liquid human milk fortifiers (LHMF), those receiving acidified LHMF (ALHMF) had a significantly higher incidence of metabolic acidosis compared to those receiving heat-treated LHMF (HTLHMF).

Despite the differences in metabolic acidosis, there were no significant variations in other clinical, nutritional, or growth outcomes between the two groups, suggesting that while ALHMF may pose risks, it does not adversely affect overall growth and nutrition in preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and nutritional outcomes of two liquid human milk fortifiers for premature infants. Lainwala, S., Kosyakova, N., Spizzoucco, AM., et al.[2018]

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]

Human milk fortification is a common practice in developed countries for preterm infants, but it is not routinely used in India due to concerns about safety and potential complications.

There is a lack of data in India regarding the safety and short-term benefits of using human milk fortifiers, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Milk Fortification in India. Kler, N., Thakur, A., Modi, M., et al.[2016]

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]

Multinutrient fortification of human milk can enhance the growth of preterm infants while they are in the hospital, but it does not appear to improve their long-term growth or neurodevelopmental outcomes.

Current evidence suggests that introducing human milk fortifiers early does not significantly impact important health outcomes, and using cow milk-based fortifiers may increase the risk of necrotizing enterocolitis (NEC) in infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Multinutrient Human Milk Fortifiers in Preterm Infants: A Systematic Review of Unanswered Questions. Mimouni, FB., Nathan, N., Ziegler, EE., et al.[2018]

Human milk is the best diet for preterm infants, providing essential nutrients and bioactive factors that support their growth and brain development, but it often requires fortification to meet their nutritional needs.

Infants receiving fortified maternal milk achieve weight gain comparable to those fed preterm formula, while those on donor milk may gain weight more slowly, highlighting the importance of optimizing human milk fortification strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preterm infant nutrition and growth with a human milk diet. Ong, ML., Belfort, MB.[2023]

Fortifying human milk is essential for preterm infants to meet their specific nutritional needs and support growth rates similar to those of fetuses at the same gestational age.

Individualized fortification methods, such as targeted/tailored and adjustable fortification, are recommended to optimize nutrient delivery and ensure adequate growth in premature infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fortification of maternal milk for preterm infants. Di Natale, C., Coclite, E., Di Ventura, L., et al.[2018]

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. Italy pubmed.ncbi.nlm.nih.gov

Update of adjustable fortification regimen for preterm infants: a new protocol. [2022]

3. 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]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical and nutritional outcomes of two liquid human milk fortifiers for premature infants. [2018]

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Human Milk Fortification in India. [2016]

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

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

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

The Use of Multinutrient Human Milk Fortifiers in Preterm Infants: A Systematic Review of Unanswered Questions. [2018]

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

Preterm infant nutrition and growth with a human milk diet. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Fortification of maternal milk for preterm infants. [2018]