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

80 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 Early Human Milk Fortification for Premature Infants?

Research shows that fortifying human milk with human milk fortifiers (HMF) can improve growth and nutritional outcomes in premature infants. Studies comparing different types of HMFs, including liquid and powdered forms, have demonstrated enhanced growth and better developmental outcomes in preterm infants, suggesting that early fortification may be beneficial. ^{1 2 3 4 5}

Is early human milk fortification safe for premature infants?

Research shows that fortifying human milk for premature infants is generally safe and helps with growth and nutrition. Studies have looked at different types of fortifiers and found them to be well-tolerated, although long-term effects on growth and development are not fully known. ^{1 3 5 6 7}

How does the treatment 'Early Human Milk Fortification for Premature Infants' differ from other treatments for premature infants?

The 'Early Human Milk Fortification for Premature Infants' treatment is unique because it involves fortifying human milk earlier than usual, which may optimize nutrition and growth in premature infants. This approach contrasts with traditional methods that delay fortification, potentially offering benefits in terms of growth and development. ^{1 4 5 6 8}

What is the purpose of this trial?

This trial is testing if giving extra protein to very preterm infants helps with their growth and gut health. The goal is to see if protein supplementation leads to better growth and a more diverse gut microbiome.

Research Team

Ariel A. Salas, MD, MSPH

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

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 birth weight was under 1800 grams.

My baby is less than 4 days old.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Enhanced growth of preterm infants fed a new powdered human milk fortifier: A randomized, controlled trial. [2019]

3. Australia pubmed.ncbi.nlm.nih.gov

Early versus delayed introduction of human milk fortification in enterally fed preterm infants: A systematic review and meta-analysis. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Concentrated Preterm Formula as a Liquid Human Milk Fortifier at Initiation Stage in Extremely Low Birth Weight Preterm Infants: Short Term and 2-year Follow-up Outcomes. [2021]

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

Feeding tolerance in premature infants fed fortified human milk. [2019]

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

Nutritional follow-up of the breastfeeding premature infant after hospital discharge. [2019]

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

A new liquid human milk fortifier and linear growth in preterm infants. [2012]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of A Concentrated Preterm Formula as a Liquid Human Milk Fortifier in Preterm Babies at Increased Risk of Feed Intolerance. [2019]