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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to fortify human milk to help preterm infants, weighing less than 1250 grams, gain weight more effectively. Researchers compare two methods: Adjustable Human Milk Fortification, which adjusts fortification based on blood tests, and Targeted Human Milk Fortification, which uses milk analysis. Infants born appropriate for their gestational age at Foothills Medical Centre and weighing less than 1250 grams might be suitable candidates. The goal is to determine which fortification method supports better growth in these tiny newborns. As an unphased trial, this study offers a unique opportunity to contribute to important research that could improve the health of preterm infants.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that both adjustable and targeted methods of adding nutrients to human milk are generally safe for premature babies. Adjustable fortification uses blood tests to determine the right nutrient levels and has been linked to better weight and head growth in some studies, indicating it is well-tolerated by infants.

Targeted fortification, in contrast, adjusts nutrient levels based on analyzing the milk itself. Research indicates that this method can help prevent serious health issues in very small premature babies, suggesting it is also safe to use.

Both methods aim to support the growth of premature infants and do not present significant safety concerns in existing research. These findings may reassure those considering participation in a trial about the safety of these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these milk fortification methods for preterm infants because they aim to optimize nutritional support in a personalized way. Traditional fortification methods are often based on fixed nutrient content, but Adjustable Human Milk Fortification is tailored to an infant's specific needs by using blood urea levels as a guide. Meanwhile, Targeted Human Milk Fortification uses detailed milk analysis to adjust nutrients. These innovative approaches could lead to better growth and development outcomes by providing more precise nutrition compared to standard, one-size-fits-all fortification methods.

What evidence suggests that this trial's treatments could be effective for preterm infants' growth?

Research has shown that adding nutrients to breast milk can help premature babies gain weight more effectively. In this trial, participants will receive either Adjustable Human Milk Fortification or Targeted Human Milk Fortification. Studies indicate that adjustable fortification, which increases protein without altering the milk's energy or volume, can enhance growth and has been linked to better growth in very low birth weight infants. Targeted fortification involves tailoring the milk based on its nutritional content, and early findings suggest this method could lead to better weight gain than adjustable methods. Both approaches in this trial aim to improve nutrition and support better growth for these tiny babies. ^{2 4 6 7 8}

Who Is on the Research Team?

Belal M Alshaikh, MD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11638827/

Narrative review of methodological advances in human milk ... Ginovart also documented that early fortification enhanced head circumference and weight gain in hospitalized preterm infants (21). In another ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6827866/

Targeted or adjustable versus standard diet fortification for ... Thus, fortification of human milk can be utilized in the NICU setting to optimize nutritional intake and improve growth outcomes for preterm infants (Agostoni ...

3. frontiersin.org frontiersin.org/journals/pediatrics/articles/10.3389/fped.2019.00076/full

Fortification of Human Milk for Preterm Infants: Update and ... Human Milk as the Best Feeding Option for Preterm Infants. Evidence-based data show that HM is the best nutritional and normative standard for infant nutrition ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04809350?tab=history&a=2

Human Milk Fortification With Adjustable Versus Targeted ... Hypothesis: Targeted fortification of human milk results in better weight gain in infants with birth weight <1250 gr when compared to the adjustable ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0378378213002119

Adjustable protein fortification of human milk A higher protein intake by adjustable protein fortification method without energy or volume change leads to improved postnatal in-hospital-growth in very low ...

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

Fortification of Human Milk for Preterm Infants: Update and ... “Adjustable Fortification” and “Targeted Fortification” are 2 methods of individualized fortification. The quality and source of human milk fortifiers ...

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

Narrative review of methodological advances in human ... The results of recent meta-analyses suggest that early fortification has little or no effect on body growth during hospitalization in very ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/16885989/

Adjustable fortification of human milk fed to preterm infants Conclusion: Premature infants managed with the new adjustable fortification regimen had significantly higher weight and head circumference gains than infants ...