Early Human Milk Fortification for Premature Infants

(ENACT+ Trial)

Overseen By Ariel A. Salas, MD, MSPH

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Disqualifiers: Small for gestational age, major anomalies, terminal illness

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 60 days or until hospital discharge

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether providing extra nutrition to very preterm infants earlier can improve growth and gut health. Researchers will compare two groups of infants: one group will receive a human milk fortifier (HMF) between days 4 and 7, while the other will start between days 10 and 14. The goal is to determine if the earlier start leads to better growth and more diverse gut bacteria. Infants eligible for this trial were born at 29 to 33 weeks of gestation and weigh less than 1800 grams. As an unphased trial, this study offers a unique opportunity to enhance understanding of optimal nutrition for 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?

Research has shown that adding extra nutrients to breast milk is generally safe for premature babies. Studies have found that using a special supplement, called a human milk fortifier, can help very small babies grow better. One study discovered that a fortifier made from cow's milk was safe and well-tolerated, even for these tiny infants.

Additionally, starting fortification early has been linked to better growth, including increases in body length and head size. These are important signs of healthy development in babies. Overall, evidence suggests that early fortification is not only safe but also helps premature infants grow better. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about early human milk fortification (HMF) for premature infants because it introduces a fortifier to the baby's diet much sooner than traditional methods. The early HMF approach starts between days 4 to 7, which could potentially enhance growth and development by providing essential nutrients earlier. This contrasts with the delayed HMF method, which begins between days 10 to 14. By advancing the timeline for fortification, early HMF might offer quicker nutritional support, potentially leading to better health outcomes for premature infants.

What evidence suggests that early human milk fortification could be effective for premature infants?

Research has shown that adding extra nutrients to breast milk early can help very premature babies grow better. In this trial, participants in the Early human milk fortification (HMF) group will receive a human milk fortifier added to feeds between days 4 and 7. This early nutrient addition is linked to increases in lean body mass, which is important for healthy growth. Some studies suggest it also supports better brain development in very low birth weight babies. Overall, early nutrient addition seems to benefit the growth and development of premature infants. Meanwhile, participants in the Delayed human milk fortification (HMF) group will receive the fortifier between days 10 and 14. ^{2 4 6 7 8}

Who Is on the Research Team?

Ariel A. Salas, MD, MSPH

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for very preterm infants with a birth weight under 1800 grams and aged less than 96 hours, born between 29 to 33 weeks of gestation. It's not suitable for babies small for their gestational age, those with terminal illnesses where support is limited, or major congenital/chromosomal anomalies.

Inclusion Criteria

My baby is less than 4 days old.

My birth weight was under 1800 grams.

I am between 29 and 33 weeks pregnant.

Exclusion Criteria

I have a significant birth defect or genetic disorder.

Small for gestational age (less than 5th percentile)

Terminal illness needing withhold or limit support

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Randomization to early or delayed human milk fortification, with fortification starting between days 4 to 7 or days 10 to 14, respectively

Up to 60 days or until hospital discharge

Follow-up

Participants are monitored for growth, microbiome composition, and health outcomes until 36 weeks postmenstrual age or hospital discharge

Up to 36 weeks postmenstrual age or hospital discharge

What Are the Treatments Tested in This Trial?

Interventions

• Delayed HMF
• Early HMF

Trial Overview

The study tests if giving very preterm infants protein supplements early (between day 4-7) versus later (day 10-14) affects their body composition and gut bacteria diversity. The trial randomly assigns infants to one of the two groups.

How Is the Trial Designed?

Group I: Early human milk fortification (HMF) group Experimental Treatment 1 Intervention

A human milk fortifier will be added to the feeds between days 4 to 7, after a total feeding volume greater than 120 ml/kg/day is achieved.

Group II: Delayed human milk fortification (HMF) group Active Control 1 Intervention

A human milk fortifier will be added to the feeds between days 10 to 14, after a total feeding volume greater than 120 ml/kg/day is achieved.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Mead Johnson Nutrition

Industry Sponsor

Trials

80

Recruited

15,900+

Published Research Related to This Trial

In a study of 144 preterm infants, those receiving a new powdered human milk fortifier (SF) showed significantly greater weight gain and length growth compared to those receiving a commercial fortifier (CF), with weight gain differences of 2.6 g/kg/day in the intent-to-treat analysis.

The new fortifier (SF) was well-tolerated and led to faster growth milestones, with infants reaching 1800 g weight at an earlier time (SDAY 18) compared to those on the CF (SDAY 25), indicating its potential as a superior nutritional supplement for preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced growth of preterm infants fed a new powdered human milk fortifier: A randomized, controlled trial. Reis, BB., Hall, RT., Schanler, RJ., et al.[2019]

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]

The new ultraconcentrated liquid human milk fortifier (LHMF) significantly improved growth metrics, such as weight and length, in preterm infants compared to a traditional powdered human milk fortifier (HMF) over a 28-day study involving 150 infants.

The LHMF was found to be safe, with no increase in the incidence of serious conditions like sepsis or necrotizing enterocolitis, while also providing about 20% more protein than the control HMF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new liquid human milk fortifier and linear growth in preterm infants. Moya, F., Sisk, PM., Walsh, KR., et al.[2012]

Citations

1.

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 ...

2.

pmc.ncbi.nlm.nih.gov

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

Fortification of Human Milk for Preterm Infants: Update and ...

Better linear growth and early gains in fat-free body mass have been found to be associated with improved neurodevelopment in VLBW preterm infants (13, 14).

3.

publications.aap.org

publications.aap.org/pediatrics/article/152/3/e2023062391/193279/Sooner-Is-Better-Early-Human-Milk-Fortification

Sooner Is Better: Early Human Milk Fortification for ...

Results indicated better growth with early milk fortification (median age at fortification, 3 days) compared with fortification at or above 120 ...

4.

withpower.com

withpower.com/trial/phase-premature-birth-9-2022-fa16e

Early Human Milk Fortification for Premature Infants · Info ...

Studies comparing different types of HMFs, including liquid and powdered forms, have demonstrated enhanced growth and better developmental outcomes in preterm ...

5.

heraldopenaccess.us

heraldopenaccess.us/openaccess/use-of-human-milk-fortifier-in-preterm-infants-in-the-community-practical-experience-from-clinical-cases

Use of human milk fortifier in preterm infants in the community

Most parents (79%) found HMF easy to use and were satisfied overall. Conclusion: The novel HMF supported infants' growth both during hospital stay and, in the ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8649601/

Evidence summary of human milk fortifier in preterm infants

Studies (27,28) have shown that appropriate use of breast milk fortifier can improve the early body weight growth rate of premature infants, ...

7.

ebneo.org

ebneo.org/ebneo-commentary-early-human-milk-fortification-in-infants-born-extremely-preterm/

Early Human Milk Fortification in Infants Born Extremely ...

Early provision of fortified human milk within the first 96 hours after birth may increase length gain velocity and reduce declines in head ...

8.

nature.com

nature.com/articles/s41372-024-01998-0

Immediate fortification of human milk with a bovine ...

In conclusion, we provide valuable clinical data that addition of a bovine milk-derived HMF is safe and well-tolerated in VLBW infants despite ...