Feeding Strategies Around Blood Transfusions for Necrotizing Enterocolitis

(WHEAT Trial)

Overseen By Cari-Lee Carnell

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: IWK Health Centre

Disqualifiers: Parental opt-out, GIT abnormality, NEC, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 34(+6) weeks gestational age

4333 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best feeding approach for very premature babies (born before 30 weeks) during blood transfusions to reduce the risk of Necrotizing Enterocolitis (NEC), a severe intestinal disease. Researchers compare two methods: continuing feeds during transfusion (Continued feeds around transfusion) or pausing feeds for a short period around the transfusion (Withholding feeds around transfusion). The trial is open to preterm infants in Canada and the UK who have not yet had a blood transfusion with feeds and have no major gut issues. As an unphased trial, this study offers a unique opportunity to contribute to important research that could improve care for very premature infants.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It focuses on feeding strategies around blood transfusions for very premature infants.

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

Research has examined the effects of both continuing and stopping feeds during blood transfusions in premature babies to assess safety. When feeds continue, researchers have investigated whether feeding during a blood transfusion increases the risk of necrotizing enterocolitis (NEC), a serious bowel condition. Some studies suggest a possible link between feeding during transfusions and NEC, but more data is needed.

Conversely, stopping feeds during transfusions might reduce the risk of NEC by lessening stress on the baby's gut. However, this idea stems from observations and lacks thorough testing in controlled studies. Concerns also exist that stopping feeds could negatively affect the baby's nutrition and growth.

Both approaches are common in neonatal care and are generally considered safe, but further research is needed to determine which is more effective in preventing NEC. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores different feeding strategies around blood transfusions for infants with necrotizing enterocolitis (NEC), a serious intestinal condition. Typically, feeding is paused during transfusions to prevent complications. However, this trial is investigating whether continuing feeds could be beneficial, potentially offering a more stable nutritional intake. By comparing continued feeding with the traditional method of withholding feeds, the trial aims to determine the safest and most effective approach, potentially leading to improved care for vulnerable infants.

What evidence suggests that this trial's treatments could be effective for reducing Necrotizing Enterocolitis?

This trial will compare two feeding strategies around the time of a blood transfusion for very premature infants to prevent necrotizing enterocolitis (NEC), a serious gut condition. One arm of the trial continues feeds during the transfusion, while the other withholds feeds. Research has shown no clear consensus on which approach is more effective. Some studies suggest that continuing feeds during a transfusion does not affect oxygen delivery to the baby's gut. However, observations indicate that stopping feeds might reduce NEC risk by lessening gut stress, though controlled studies have not proven this potential benefit. Both methods are currently used in hospitals, highlighting the ongoing debate about the best approach. ^{1 2 3 4 6}

Who Is on the Research Team?

Balpreet Singh, MD

Principal Investigator

IWK Health, Canada

Jon Dorling, MD

Principal Investigator

Princess Anne Hospital, UK

Chris Gale, MD

Principal Investigator

Imperial College London, UK

Are You a Good Fit for This Trial?

This trial is for very premature infants born before 30 weeks of gestation. It's not suitable for babies with major GIT abnormalities, those whose parents opt out, or who have had a blood transfusion with feeds or a previous episode of NEC/SIP before their first transfusion.

Inclusion Criteria

Preterm birth at <30+0 gestational weeks + days

Exclusion Criteria

I had NEC or an intestinal tear before my first blood transfusion.

My parents have decided I will not participate in the trial.

My infant cannot be fed through the mouth or stomach due to a major birth defect in the digestive system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Infants are randomized to either withhold or continue enteral feeds around blood transfusion until 34(+6) weeks gestational age

Up to 34(+6) weeks gestational age

Follow-up

Participants are monitored for safety and effectiveness after treatment, including NEC, ROP, severe brain injury, and other outcomes

From randomization to 40 weeks postmenstrual age

What Are the Treatments Tested in This Trial?

Interventions

• Continued feeds around transfusion
• Withholding feeds around transfusion

Trial Overview The WHEAT International trial is testing if withholding enteral feeds around the time of a blood transfusion reduces the risk of Necrotizing Enterocolitis in preterm infants compared to continuing feeding during transfusions.

How Is the Trial Designed?

Group I: Continuing feeds around transfusion Active Control 1 Intervention

Enteral feeds will continue to be given prior, during and after the packed red cell transfusion, in the manner in which they were being given prior to the decision to transfuse. Infants will remain allocated to the same care pathway until 34(+6) weeks(+days) gestational age.

Group II: Withholding feeds around transfusion Active Control 1 Intervention

All enteral feeds will be discontinued (the infant will be placed nil by mouth) for 4 hours prior to packed red cell transfusion, during the transfusion and until 4 hours post transfusion. During this period, hydration and blood glucose will be maintained according to local practice, commonly by providing parenteral nutrition or intravenous dextrose. Four hours after the red cell transfusion has finished, feeds will be recommenced to how they were being received prior to the decision to transfuse. This duration of withholding feeds will follow the approach used in other trials and observational studies, and identified as the most acceptable in a survey of UK neonatal units. It gives time for milk in the small bowel to transit into the large bowel before the transfusion and for the circulation to stabilize after the transfusion before milk feeds given into the stomach pass through into the small intestine.

Who Is Running the Clinical Trial?

IWK Health Centre

Lead Sponsor

Trials

131

Recruited

112,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Imperial College London

Collaborator

Trials

1,052

Recruited

15,030,000+

Published Research Related to This Trial

Preterm infants who developed necrotizing enterocolitis (NEC) were more likely to have received red blood cell (RBC) transfusions in the 48 to 72 hours before their diagnosis, with significant differences observed (56% vs 20% within 48 hours, P=0.019).

Implementing a policy of withholding feeds during RBC transfusions significantly reduced the incidence of NEC from 5.3% to 1.3%, suggesting that this practice may offer a protective effect against the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Red blood cell transfusion, feeding and necrotizing enterocolitis in preterm infants. El-Dib, M., Narang, S., Lee, E., et al.[2014]

In a study of 108 very low-birth-weight infants, withholding feedings during blood transfusions did not significantly reduce the incidence of necrotizing enterocolitis (NEC), with 7.8% of those with withheld feeds developing NEC compared to 13.8% of those who were fed.

While there was a 6% absolute difference in NEC rates that could be clinically important, the results were not statistically significant, suggesting that withholding feeds may not be an effective strategy and could lead to other complications like the need for intravenous access.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feeding during Blood Transfusions and the Association with Necrotizing Enterocolitis. Doty, M., Wade, C., Farr, J., et al.[2018]

Withholding feeding during red blood cell transfusions in preterm infants may help reduce the risk of developing transfusion-associated necrotising enterocolitis, although the evidence is currently limited.

The ongoing WHEAT trial aims to provide clearer answers on this practice, allowing individual medical units to make informed decisions in the meantime.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do feeding practices during transfusion influence the risk of developing necrotising enterocolitis in preterm infants? Hilditch, C., Keir, A.[2019]

A systematic review identified only one eligible randomized controlled trial (RCT) involving 22 preterm infants that examined the effects of stopping feeds during blood transfusion, but it did not report any cases of necrotizing enterocolitis (NEC).

The evidence is currently insufficient to determine whether withholding feeds around the time of blood transfusion affects the incidence of NEC or mortality in preterm infants, highlighting the need for larger, well-designed RCTs to clarify this issue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stopping enteral feeds for prevention of transfusion-associated necrotising enterocolitis in preterm infants. Yeo, KT., Kong, JY., Sasi, A., et al.[2021]

In a pilot study involving 112 preterm infants, withholding enteral feeding during red blood cell transfusion did not significantly reduce the rates of necrotizing enterocolitis (NEC) compared to continuing feeding, with NEC rates at 0% in the NPO group and 3.4% in the FED group.

The study found no significant differences in abdominal circumference or feeding intolerance between the two groups, suggesting that withholding feedings during transfusion may not be necessary, but further research with larger sample sizes is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of withholding feeds on transfusion-related acute gut injury in preterm infants: a pilot randomized controlled trial. Sahin, S., Gozde Kanmaz Kutman, H., Bozkurt, O., et al.[2021]

In a study involving 41 preterm infants, different enteral feeding regimens during red cell transfusions did not significantly affect splanchnic oxygenation or clinical outcomes, indicating that feeding practices may be safely adjusted during transfusions.

Despite no differences in oxygenation metrics or the occurrence of necrotising enterocolitis (NEC) among the feeding groups, the study's design supports the potential for larger trials to further investigate clinical outcomes related to transfusion practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FEEding DURing red cell transfusion (FEEDUR RCT): a multi-arm randomised controlled trial. Schindler, T., Yeo, KT., Bolisetty, S., et al.[2021]

Withholding feeds during packed red blood cell (PRBC) transfusions in preterm infants may significantly reduce the incidence of transfusion-associated necrotizing enterocolitis (TANEC), based on a meta-analysis of 7 non-randomized controlled trials involving 7492 infants.

The evidence supporting this practice is of moderate quality, indicating a need for further research, particularly randomized controlled trials, to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Withholding Feeds and Transfusion-Associated Necrotizing Enterocolitis in Preterm Infants: A Systematic Review. Jasani, B., Rao, S., Patole, S.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6815687/

Stopping enteral feeds for prevention of transfusion ... In preterm infants, does stopping feeds around the time of a packed red blood cell transfusion result in decreased risk of developing necrotising enterocolitis ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05213806

WithHolding Enteral Feeds Around Blood Transfusion ... Withholding milk feeds during red cell transfusion may reduce the risk of NEC by decreasing postprandial mesenteric ischemia but there may be harmful effects of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7359615/

FEEding DURing red cell transfusion (FEEDUR RCT) There were no differences in splanchnic oxygenation when enteral feeds were either withheld, continued or restricted during a transfusion.

4. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012888.pub2/full

Stopping enteral feeds for prevention of transfusion ... The effects of feeding a baby during a red cell transfusion and subsequent development of NEC are currently unclear, and significant practice ...

5. sciencedirect.com sciencedirect.com/science/article/am/pii/S0095510823000556

Red Blood Cell Transfusion, Anemia, Feeding and the Risk ... In this review, we summarize data on feeding during red blood cell transfusion and its role in NEC and highlight ongoing randomized trials. Key Points.

6. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1408717/full

Effects of the feeding protocol during blood transfusion on ... Packed RBC transfusions, enteral feedings, and gastrointestinal immaturity are all risk factors for TA-NEC (8). Anemia can lead to intestinal ...