Early Feeding for Very Low Birth Weight Infants

Overseen By Ihinosen Edgal, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Tennessee

Must not be taking: Pressors

Disqualifiers: Congenital malformations, Imminent death, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 30 days

248 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether feeding very low birth weight infants (weighing 1000 grams or less at birth) within 6 hours of birth helps them reach full feeding sooner than the current practice of starting at 3 days. The goal is to determine if this early feeding approach can improve growth and health outcomes without increasing risks. Infants weighing 1000 grams or less, with care team approval, might be suitable for this trial. As an unphased trial, this study provides a unique opportunity to contribute to important research that could enhance care for future 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.

What prior data suggests that early enteral feeding is safe for very low birth weight infants?

Research has shown that starting feedings early for very low birth weight (VLBW) infants is generally safe. One study found that earlier feeding was linked to a lower risk of serious bowel problems, such as necrotizing enterocolitis (NEC), or death. Another study showed that most infants began feeding within the first 24 hours of life without added risks.

Concerns have existed that early feeding could lead to negative outcomes. However, data suggests that starting feeds earlier might help infants handle feeding better and grow faster without increasing the risk of NEC.

In summary, evidence indicates that early feeding is well-tolerated and does not increase the risk of serious issues in VLBW infants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the early feeding protocol for very low birth weight infants because it could potentially improve outcomes by jumpstarting the digestive process much sooner than usual. Typically, feeding such infants happens after a day or more to avoid complications, but starting feeds within 6 hours may strengthen the gut and enhance nutrition uptake. By implementing this early feeding method, researchers hope to reduce the risk of complications like infections and promote better growth and development in these vulnerable infants.

What evidence suggests that starting feeds within 6 hours of life is effective for very low birth weight infants?

This trial will compare early feeding with standard feeding practices for very low birth weight infants. Research has shown that starting to feed these infants early can greatly improve their health. Studies have found that beginning feeds sooner is linked to a lower risk of necrotizing enterocolitis, a serious intestinal disease, or even death. Evidence also suggests that early feeding helps these infants reach full feeding amounts faster, gain weight more quickly, and reduces the chance of infections like sepsis. Additionally, early feeding does not increase the risk of complications and supports better growth outside the womb. Overall, early feeding offers several benefits for the health and development of these infants. ^{1 5 6 7 8}

Who Is on the Research Team?

Mohamad Elabiad, MD

Principal Investigator

UTHSC

Are You a Good Fit for This Trial?

This trial is for premature infants weighing ≤ 1000g at birth. It's designed to see if starting feeds within the first 6 hours of life, compared to the standard practice of waiting up to 3 days, helps them reach full volume feeds sooner in their first month.

Inclusion Criteria

Clinical care team in agreement with patient's participation

All mothers with pregnancies with estimated fetal weight close to 1000g or less.

My infant weighs 1000 g or less.

Exclusion Criteria

Clinical progression towards imminent death

Mothers who are not in a sound mental state to be consented either to their critical condition, intubated, sedated, for example

Mothers unlikely to deliver infants ≤ 1000g

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 days

Treatment

Infants are randomized to early feeding or standard protocol feeding. Early feeding starts within 6 hours of life.

30 days

Continuous monitoring in NICU

Follow-up

Participants are monitored for safety and effectiveness after treatment until hospital discharge

Up to 20 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Starting feeds within 6 hours of life

Trial Overview

The study tests two feeding protocols for extremely low birth weight (ELBW) infants: one starts feeding within 6 hours after birth and the other follows a standard protocol. The goal is to determine which method leads to quicker advancement to full volume feeds without increasing health risks.

How Is the Trial Designed?

Group I: Early feeding arm Experimental Treatment 1 Intervention

Group II: Control arm Active Control 1 Intervention

Who Is Running the Clinical Trial?

University of Tennessee

Lead Sponsor

Trials

202

Recruited

146,000+

Published Research Related to This Trial

Early enteral feeding in very-low-birth-weight (VLBW) infants was found to be safe, with no cases of necrotizing enterocolitis (NEC) reported, suggesting it does not increase the risk of this serious condition.

The study demonstrated that early enteral feeding can support healthy weight gain in VLBW infants, with those in the study exceeding their birth weight by significant amounts by the 30th postnatal day, although some infants experienced feeding intolerance, indicating that additional parenteral nutrition might be beneficial for certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with early enteral feeding in very-low-birth-weight infants. Wang, LY., Hung, HY., Hsu, CH., et al.[2015]

A quality improvement initiative successfully reduced the median time to initiate enteral feeding in very low birth weight (VLBW) infants from 33 hours to 14 hours, without increasing the risk of necrotizing enterocolitis (NEC) or death.

Initiating enteral feeding within the first 24 hours was linked to a significant reduction in the incidence of NEC or death (6.3% vs. 15.1%), suggesting that earlier feeding may improve outcomes for VLBW infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early enteral feeding in very low birth weight infants. Hamilton, E., Massey, C., Ross, J., et al.[2022]

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]

Starting early total enteral nutrition (80 mL/kg/d) on the first day of life in hemodynamically stable very-low-birth-weight (VLBW) neonates significantly reduces the time to achieve full feeds (180 mL/kg/d), with the intervention group reaching this goal in a median of 6 days compared to 10 days in the control group.

The study involved 60 VLBW neonates and demonstrated that rapid advancement of feeds is safe and effective, leading to quicker nutritional support without increasing the risk of complications like necrotizing enterocolitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Total Versus Gradually Advanced Enteral Nutrition in Stable Very-Low-Birth-Weight Preterm Neonates: A Randomized, Controlled Trial. Jajoo, M., Singh, A., Arora, N., et al.[2022]

Early enteral feedings in very-low-birth-weight or sick preterm infants, initiated within 4 days of birth, did not show significant effects on weight gain, necrotizing enterocolitis (NEC), mortality, or age at discharge based on two small studies (totaling 72 patients).

However, early feedings were associated with some potential benefits, such as fewer days on parenteral nutrition and reduced need for gastric suction and sepsis evaluations, suggesting that while the overall impact remains uncertain, there may be advantages to early feeding practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early versus delayed initiation of progressive enteral feedings for parenterally fed low birth weight or preterm infants. Kennedy, KA., Tyson, JE., Chamnanvanikij, S.[2018]

Starting enteral nutrition within 3 days for very low birth weight infants (VLBWI) leads to significantly higher milk intake and a lower rate of nosocomial infections (13.8%) compared to starting after 7 days (46.2%).

While the timing of enteral nutrition does not affect growth rates, early initiation (≤ 3 days) promotes better gastrointestinal function and reduces the duration of central venous catheterization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of enteral nutrition starting time on digestive function and growth rate in very low birth weight infants]. Yu, XY., Fan, L.[2014]

The standardized slow enteral feeding (SSEF) protocol significantly reduced the incidence of necrotizing enterocolitis (NEC) and combined NEC/death in extremely low birth weight (ELBW) infants weighing less than 750 g, compared to historical controls.

Although the SSEF group took longer to reach full enteral feeding and had longer parenteral nutrition and central line days, there was no difference in weight gain at discharge or length of hospital stay for surviving infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standardized Slow Enteral Feeding Protocol and the Incidence of Necrotizing Enterocolitis in Extremely Low Birth Weight Infants. Viswanathan, S., McNelis, K., Super, D., et al.[2022]

A systematic review of six trials involving 526 preterm or low birth weight infants found that early full enteral feeding did not significantly increase the risk of necrotising enterocolitis compared to delayed feeding, indicating it may be a safe option.

The evidence regarding the impact of early full enteral feeding on growth rates was inconclusive, with some studies showing faster weight gain while others indicated slower rates, highlighting the need for further research to clarify these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early full enteral feeding for preterm or low birth weight infants. Walsh, V., Brown, JVE., Copperthwaite, BR., et al.[2022]

In a randomized clinical trial involving 50 growth-restricted preterm infants, those who received early enteral feeding reached full feeding significantly faster and regained birth weight more quickly compared to those who were fed later.

Early feeding was associated with a lower incidence of neonatal sepsis, reduced feeding intolerance, shorter hospital stays, and better weight gain by day 16, indicating that it is a safe and beneficial practice for these vulnerable infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Versus Delayed Enteral Feeding for Achieving Full Feeding in Preterm Growth-Restricted Infants: A Randomized Clinical Trial. Ahmed, F., Dey, SK., Shahidullah, M., et al.[2020]

In a study of 150 very low birthweight preterm infants, feeding every 2 hours did not significantly reduce the time to achieve full enteral feeding compared to feeding every 3 hours, with times of 10.2 days and 11.3 days respectively.

However, infants fed every 3 hours regained their birth weight faster than those fed every 2 hours, taking an average of 12.9 days compared to 14.8 days, indicating that 3-hourly feeding may be more beneficial for weight recovery without increasing adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-hourly versus 3-hourly feeding for very low birthweight infants: a randomised controlled trial. Ibrahim, NR., Kheng, TH., Nasir, A., et al.[2017]

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.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/24612934/

Early enteral feeding in very low birth weight infants

When controlling for birth weight, gestational age, race, gender, and time period, earlier feed initiation was associated with decreased NEC or death (p=0.003).

2.

publications.aap.org

publications.aap.org/pediatrics/article/149/1%20Meeting%20Abstracts%20February%202022/664/186584/Early-Enteral-Feeds-Achievement-by-Reducing-Time

Early Enteral Feeds Achievement by Reducing Time to ...

Meta-analysis of the Impact of Early Enteral Nutrition on the Clinical Outcomes of Very Low Birth Weight Premature Infants. Shuang Fang, Libo ...

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cochranelibrary.com

cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013542.pub2/full

Early full enteral feeding for preterm or low birth weight ...

Conclusion: there is not enough evidence to determine whether early full milk feeds benefit preterm or low birth weight infants. New trials ...

4.

researchgate.net

researchgate.net/publication/260556338_Early_enteral_feeding_in_very_low_birth_weight_infants

Early enteral feeding in very low birth weight infants

Early enteral feeding has been associated with improved survival and postnatal growth, decreased incidence of sepsis and necrotizing ...

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withpower.com

withpower.com/trial/phase-premature-birth-5-2024-63442

Early Feeding for Very Low Birth Weight Infants

Research shows that starting early feeding in very low birth weight infants can help them reach full feeding faster, gain weight more quickly, and reduce the ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S0899900722003240

Effect of early initiation of enteral nutrition on short-term ...

A multicenter study in China showed that the average time of initiating enteral feeding in very-low-birth-weight infants was approximately 24 h after birth [22] ...

7.

researchgate.net

researchgate.net/publication/362460107_Early_Enteral_Feeding_for_Preterm_or_Low_Birth_Weight_Infants_a_Systematic_Review_and_Meta-analysis

Early Enteral Feeding for Preterm or Low Birth Weight Infants

CONTEXT Early enteral feeding has been associated with adverse outcomes such as necrotizing enterocolitis in preterm and low birth weight ...

8.

mdpi.com

mdpi.com/2072-6643/16/23/4041

Hour of Life at Enteral Feeding Initiation and Associated ...

Demographic and clinical outcome data are reported in Table 1 and Table 2. A total of 83.6% of all infants initiated enteral feeding within the first 24 h of ...