Enteral Nutrition for Premature Birth

(ENACT Trial)

Overseen By Ariel Salas, MD, MSPH

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Disqualifiers: Intrauterine growth restriction, Congenital anomalies, Terminal illness

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if early exclusive enteral nutrition (feeding through the stomach) improves nutritional outcomes for preterm infants compared to a slower introduction. Researchers are testing two groups: one receives higher feeding volumes immediately after birth, while the other starts with lower volumes. Babies born between 28 and 32 weeks, without major birth defects or severe growth problems, may be eligible to participate.

As an unphased trial, this study provides a unique opportunity to advance nutritional care for preterm infants.

Will I have to stop taking my current medications?

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

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

Research has shown that feeding very preterm infants only milk or formula directly into their stomachs, known as exclusive enteral nutrition, is generally well-tolerated. One study found that this method can lead to more days of full feeding and better muscle growth. However, questions remain about its long-term safety and effects.

For progressive enteral nutrition, where feeding amounts increase gradually, research indicates positive effects on growth and health. Starting this method early, especially with human milk, has been linked to a lower risk of necrotizing enterocolitis (NEC), a serious gut problem in preterm babies.

Both feeding methods have evidence supporting their safety and benefits, but ongoing studies aim to confirm these findings and address any remaining concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they explore different approaches to feeding premature infants, which could improve their growth and development. Exclusive Enteral Nutrition starts feeding infants larger volumes earlier, which might promote faster weight gain and better digestive health compared to traditional methods. On the other hand, Progressive Enteral Nutrition follows a more gradual increase in feeding volumes, which is closer to current practices but still aims to optimize nutrition delivery. By comparing these methods, scientists hope to identify the best strategy for supporting the health of premature babies.

What evidence suggests that this trial's treatments could be effective for premature birth?

This trial will compare Exclusive Enteral Nutrition with Progressive Enteral Nutrition for premature infants. Research has shown that starting feeding early for preterm infants helps them reach full feeding faster, benefiting their growth. Early feeding also results in more days on full feeding and healthy weight gain. Exclusive Enteral Nutrition, one method in this trial, aims to improve nutrition and support growth in premature infants. Progressive Enteral Nutrition, another approach in this trial, has shown positive results as well. It can reduce the number of days infants need intravenous feeding and help them start full oral feeding sooner, allowing earlier discharge. Both methods aim to enhance nutrition and support growth in premature infants. ^{1 3 4 6 7}

Who Is on the Research Team?

Vivek Shukla, MD

Principal Investigator

University of Alabama at Birmingham

Ariel Salas, MD, MSPH

Principal Investigator

University of Alabama at Birmingham

Jacqueline Razzaghy, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for preterm infants born between 28 and 32 weeks of gestation. It's not suitable for babies with growth restrictions (birth weight below the 10th percentile), major birth defects, or those with terminal illnesses where life support is limited.

Inclusion Criteria

Gestational age between 28 and 32 weeks of gestation

Exclusion Criteria

I do not have major birth defects or genetic disorders.

Intrauterine growth restriction (birth weight < 10th percentile)

You have a serious illness and have decided to stop receiving treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either exclusive or progressive enteral nutrition with supplemental parenteral nutrition as needed

28 days

Daily monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including weight, head circumference, and length measurements

32 days

Weekly visits

What Are the Treatments Tested in This Trial?

Interventions

• Exclusive Enteral Nutrition
• Progressive Enteral Nutrition

Trial Overview The study compares two feeding strategies in premature babies: one group will start early on exclusive enteral nutrition (feeding through the gut) minimizing parenteral nutrition (IV feeding), while another group will have a delayed progression to enteral nutrition.

How Is the Trial Designed?

Group I: Exclusive Enteral Nutrition Experimental Treatment 1 Intervention

This group will receive enteral feeding volumes at a rate of 60-80 ml/kg/day starting within the first 24 hours after birth. Volumes will increase by 20-30 ml/kg/day until intake is 150ml/kg/day.

Group II: Progressive Enteral Nutrition Active Control 1 Intervention

This group will receive enteral feeding volumes at a rate of 20-30 ml/kg/day starting within the first 24 hours after birth. Volumes will increase by 20-30 ml/kg/day until intake is 150ml/kg/day.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

A study of 293 preterm infants under 1500 g birthweight showed that implementing a rapid enteral feeding protocol led to faster achievement of full feedings and earlier weight regain without increasing the risk of feeding-related complications.

Infants in the rapid feeding group were more successfully stabilized on noninvasive ventilation and did not require mechanical ventilation, indicating that this feeding approach is safe and effective for improving clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compatibility of rapid enteral feeding advances and noninvasive ventilation in preterm infants-An observational study. Behnke, J., Estreich, V., Oehmke, F., et al.[2022]

The guideline offers evidence-based recommendations for providing essential nutrition to critically ill neonates through enteral (EN) and parenteral (PN) methods, ensuring they receive the necessary energy and nutrients when oral feeding is not possible.

For premature and very low birth weight infants facing challenges like delayed gastric emptying and respiratory issues, PN therapy is crucial, and the guideline includes specific formulas to calculate calorie supplementation when combining PN and EN support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chinese guideline for newborn nutrition support in neonates]. [2008]

Early enteral feeding within 48 hours after birth and progressive feeding before 4 days of life in clinically stable very preterm and very low birthweight infants is safe and does not increase the risk of necrotising enterocolitis (NEC) or mortality.

There is limited evidence for feeding practices in high-risk infants, such as those born small for gestational age, and future studies should focus on objective outcomes to reduce bias in assessing the safety and efficacy of enteral feeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early enteral feeding in preterm infants. Kwok, TC., Dorling, J., Gale, C.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11186726/

Early and exclusive enteral nutrition in infants born very ... This study suggests that early and exclusive enteral nutrition in very preterm infants leads to more full enteral feeding days, improved lean mass accretion, ...

2. thelancet.com thelancet.com/journals/lanchi/article/PIIS2352-4642(25)00271-8/fulltext

Full exclusively enteral fluids from day 1 versus gradual ... For the key secondary outcomes, there was no difference in survival to discharge, late-onset sepsis, necrotising enterocolitis, hypoglycaemia, ...

3. sfnmjournal.com sfnmjournal.com/article/S1744-165X(25)00025-3/abstract

Exclusive enteral nutrition in preterm infants: How early is too ... Abstract. With the growing availability of maternal and donor milk, neonatal feeding practices are undergoing significant transformation.

4. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1449022/full

Improving growth in preterm infants through nutrition The study concluded that newborns who were fed early (within the first 2 days after birth) achieved full enteral feeding more quickly than newborns fed later (5 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0378378223001767

Outcomes in very preterm infants receiving an exclusive ... This study compared unfortified pasteurised human donor milk and formula supplements. The principal outcome was survival to 34w postmenstrual age without ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1744165X25000253

Exclusive enteral nutrition in preterm infants: How early is ... This review consolidates the evidence supporting early and exclusive enteral nutrition, exploring its potential to redefine neonatal care practices.

7. espghan.org espghan.org/dam/jcr:092f7f5a-6557-433c-98d6-7259ab1a9cfa/Enteral%20Nutrition%20in%20Preterm%20Infants%202022%20A.204.pdf

Enteral Nutrition in Preterm Infants (2022) Studies suggest that the optimal enteral PER for preterm infants is 2.8 - 3.6g/100kcal (19, 38), with PERs at the higher end of this range associated with ...