ClinicalTrials.gg
RecruitingNCT05213806WHEATUpdated Sep 29, 2026

WithHolding Enteral Feeds Around Blood Transfusion (International)

An interventional study of Withholding feeds around transfusion and Continued feeds around transfusion in Necrotizing Enterocolitis, sponsored by IWK Health Centre. Recruiting at 40 sites in 2 countries. Open to participants aged Up to 30 Weeks. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by IWK Health Centre · Not applicable, Interventional, and Other

From the registry’s dates

  • Started Jan 2022; still recruiting 4 years 9 months later.
Phase
Not applicable
Study type
Interventional
Enrollment
4,333
Allocation
Randomized
Ages
Up to 30 Weeks
Sex
All
01

Study summary

The WHEAT International trial is a comparative effectiveness trial exploring whether withholding enteral feeds around the time of blood transfusion in very premature infants (\<30 weeks) will reduce the occurrence of Necrotizing Enterocolitis (NEC). Currently both continued feeding and withholding feeding are approved care practices. The current study will randomize infants from Neonatal Intensive Care Units (NICUs) across Canada and the United Kingdom (UK) into one of the two care approaches (withholding or continued feeds) to determine if any significant outcomes are found.

Read the detailed description

BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating disease that affects mostly the intestine of premature infants. The wall of the intestine is invaded by bacteria, which cause local infection and inflammation that can ultimately destroy the wall of the bowel (intestine). NEC is among the most potentially devastating neonatal diseases and has a mortality of up to 33%, the most severe form (requiring surgery or resulting in death) affects about 5% of infants born at less than 30 gestational weeks; survivors are at high risk of long-term health and developmental problems. Prevention of NEC has been identified as one of the most important research uncertainties in the field of preterm birth. A temporal association between red cell transfusion and the subsequent development of the disease is well described. This 'transfusion-associated NEC' may also be more severe with higher mortality. Very preterm or extremely low birth weight infants are among the most frequently transfused patients: between 56% and 90-95% have at least one transfusion, and those transfused received an average of 5 transfusions in their neonatal stay. 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 pausing enteral feeds. However, due to a lack of good quality evidence, there is no consensus regarding the optimal feeding strategy during a blood transfusion.

Both comparator pathways of care are standard practice in Canada and the UK; the WHEAT trial is a comparative effectiveness trial. The two care pathways that will be compared are:

  1. Withholding Feeds Around Transfusion: 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 packed red cell transfusion and until 4 hours post packed red cell transfusion.
  2. Continuing Feeds Around Transfusion: 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.

02

Conditions studied

  • Necrotizing Enterocolitis

Keywords

  • Comparative Effectiveness Trial
  • Necrotizing Enterocolitis
  • Premature Infants
  • Blood Transfusion
  • Withholding enteral feeds
03

In context

Enterocolitis, Necrotizing

228 studies on the registry are indexed under Enterocolitis, Necrotizing; 44 are open to participants now.

This study's planned enrollment of 4,333 is above the median of 103 across 127 interventional studies indexed under Enterocolitis, Necrotizing.

Browse Enterocolitis, Necrotizing studies →

Lead sponsor

IWK Health Centre is the lead sponsor of 86 studies on the registry; 14 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 30 Weeks
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

1. Preterm birth at \<30+0 gestational weeks + days

Exclusion criteria

Exclusion Criteria:

  1. Parent(s) opt-out of trial participation.
  2. Packed red cell transfusion with concurrent enteral feeds prior to enrolment. (Infants who have received a packed red cell transfusion while nil-by-mouth are eligible; or minimal enteral nutrition (\<15 ml/kg/day feeds) at the time of transfusion; defined as before, during and for at least 4 hours after transfusion, are eligible.
  3. Infants who are not being fed at the time of randomization (\<15ml/kg) or where enteral feeding is [e.g. Major congenital abnormality of the gastrointestinal tract (GIT)].
  4. Previous episode of NEC Bell stage 2 or higher or SIP prior to first study packed cell transfusion.
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

05

Study design

Phase
Not applicable
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
4,333 participants (estimated)

Study arms

  • Active comparator
    Withholding feeds around transfusion

    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.

    Other: Withholding feeds around transfusion

  • Active comparator
    Continuing feeds around transfusion

    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.

    Other: Continued feeds around transfusion

Interventions

  • OtherWithholding feeds around transfusion

    Withholding enteral feeds for preterm infants (\<30 weeks) around the time of blood transfusions to determine if any impact on the development and/or severity of Necrotizing Enterocolitis.

  • OtherContinued feeds around transfusion

    Continued enteral feeds

06

What researchers measure

Primary outcomes

  1. NEC Stage II

    Stage II or greater NEC recorded after the first trial blood transfusion; defined according to the modified Bell staging criteria: based on clinical features and abdominal imaging findings, or on surgical or histological findings of NEC.

    Time frame: From randomization to 40 weeks postmenstrual age

Secondary outcomes

  1. Severe NEC

    Histologically or surgically confirmed or recorded on the death certificate. These infants will be identified as described in Battersby et al. which will include infants recorded as being transferred for surgery.

    Time frame: From randomization to 40 weeks postmenstrual age

  2. Death

    All-cause mortality

    Time frame: From randomization to 40 weeks postmenstrual age

  3. Late onset sepsis

    Culture positive sepsis, onset after 72 hours of life

    Time frame: From randomization to 40 weeks postmenstrual age

  4. Number of days with a central venous line in situ

    Number of days with a central venous line in situ

    Time frame: From birth to date of discharge home

  5. Number of central line associated bloodstream infections

    Number of central line associated bloodstream infections: Positive blood culture confirmed bloodstream infection

    Time frame: From randomization to 40 weeks postmenstrual age

  6. Duration of any parenteral nutrition in days

    Duration of any parenteral nutrition in days

    Time frame: From birth to 40 weeks postmenstrual age

  7. Growth

    Weight and head circumference z score.

    Time frame: At date of discharge home

  8. Spontaneous Intestinal Perforation

    Histologically or surgically confirmed or recorded in the death certificate.

    Time frame: From randomization to 40 weeks postmenstrual age

  9. Duration of hospital stay

    Total duration of neonatal care in days including all levels of care (intensive care, high dependency care, special care and ordinary care)

    Time frame: From birth to date of discharge home

  10. Bronchopulmonary Dysplasia (BPD)/Chronic Lung Disease

    Requiring respiratory support at 36 weeks gestation

    Time frame: At 36 weeks postmenstrual age

  11. Retinopathy of prematurity (ROP)

    ROP requiring treatment

    Time frame: From randomization to 40 weeks postmenstrual age

  12. Severe Brain Injury

    Intraventricular haemorrhage (IVH) grade 3 or 4 or cystic periventricular leukomalacia (PVL)

    Time frame: At 40 weeks postmenstrual age

07

Study locations

40 of 40 sites recruiting
  • IWK Health
    Halifax, Nova Scotia B3K 6R8, Canada
    Recruiting
  • Norfolk & Norwich University Hospitals NHS Foundation Trust (Norfolk & Norwich University Hospital)
    Norwich, England, United Kingdom
    Recruiting
  • The Hillingdon Hospitals NHS Foundation Trust (Hillingdon Hospital)
    Hillingdon, UK, United Kingdom
    Recruiting
  • Barts Health NHS Trust (3 Hospitals: Royal London Hospital, Whipps Cross Hospital, Newham General Hospital)
    London, UK, United Kingdom
    Recruiting
  • Chelsea and Westminster Hospital NHS Foundation Trust (Chelsea and Westminster Hospital)
    London, UK, United Kingdom
    Recruiting
  • Imperial College Healthcare NHS Trust (2 Hospitals: St Mary's Hospital & Queen Charlotte's and Chelsea Hospital)
    London, UK, United Kingdom
    Recruiting
  • Bedfordshire Hospitals NHS Foundation Trust (Luton & Dunstable University Hospital)
    Luton, UK, United Kingdom
    Recruiting
  • East Kent University Hospitals NHS Foundation Trust (William Harvey Hospital)
    Ashford, United Kingdom
    Recruiting
  • Buckinghamshire Healthcare NHS Trust (Stoke Mandeville Hospital)
    Aylesbury, United Kingdom
    Recruiting
  • Barnsley Hospital NHS Foundation Trust
    Barnsley, United Kingdom
    Recruiting
  • Birmingham Women's and Children's NHS Foundation Trust (Birmingham Women's Hospital NICU)
    Birmingham, United Kingdom
    Recruiting
  • University Hospitals Birmingham NHS Trust (2 Hospitals: Heartland's Hospital & Good Hope Hospital)
    Birmingham, United Kingdom
    Recruiting
  • Bradford Teaching Hospitals NHS Foundation Trust (Bradford Royal Infirmary)
    Bradford, United Kingdom
    Recruiting
  • North Bristol NHS Trust (Southmead Hospital)
    Bristol, United Kingdom
    Recruiting
  • East and North Essex NHS Foundation Trust - Colchester Hospital
    Colchester, United Kingdom
    Recruiting
  • University Hospital Coventry & Warwickshire NHS Trust (University Hospital Coventry)
    Coventry, United Kingdom
    Recruiting
  • University Hospitals of Derby and Burton NHS Trust (Royal Derby Hospital)
    Derby, United Kingdom
    Recruiting
  • NHS Tayside (Ninewells Hospital)
    Dundee, United Kingdom
    Recruiting
  • Medway Hospital NHS Foundation Trust (Oliver Fisher Neonatal Unit, Medway Maritime Hospital)
    Gillingham, United Kingdom
    Recruiting
  • Gloucestershire Hospitals NHS Foundation Trust (Gloucestershire Royal Hospital)
    Gloucester, United Kingdom
    Recruiting
  • Calderdale & Huddersfield NHS Foundation Trust (Calderdale Royal Hospital)
    Halifax, United Kingdom
    Recruiting
  • East and North Essex NHS Foundation Trust - Ipswich Hospital
    Ipswich, United Kingdom
    Recruiting
  • Leeds Teaching Hospitals NHS Trust (Leeds General Infirmary & St James' University Hospital)
    Leeds, United Kingdom
    Recruiting
  • University Hospitals of Leicester NHS Trust (Leicester Royal Infirmary)
    Leicester, United Kingdom
    Recruiting
  • Liverpool Women's Hospital NHS Foundation Trust (Liverpool Women's Hospital)
    Liverpool, United Kingdom
    Recruiting
  • North West London NHS Trust (Northwick Park Hospital)
    London, United Kingdom
    Recruiting
  • Manchester University NHS Foundation Trust (2 Hospitals: St Mary's Hospital - Oxford Road, North Manchester General)
    Manchester, United Kingdom
    Recruiting
  • Manchester University NHS Foundation Trust (Wythenshawe)
    Manchester, United Kingdom
    Recruiting
  • The Newcastle Upon Tyne Hospitals NHS Foundation Trust (Royal Victoria Infirmary)
    Newcastle upon Tyne, United Kingdom
    Recruiting
  • Nottingham University Hospitals NHS Trust (2 Hospitals: City Hospital, Queen's Medical Centre)
    Nottingham, United Kingdom
    Recruiting
  • Oxford University Hospitals NHS FT (John Radcliffe Hospital)
    Oxford, United Kingdom
    Recruiting
  • North West Anglia NHS Trust (Peterborough City Hospital)
    Peterborough, United Kingdom
    Recruiting
  • Portsmouth University Hospitals NHS Trust (Queen Alexandra Hospital)
    Portsmouth, United Kingdom
    Recruiting
  • Lancashire Teaching Hospitals NHS Foundation Trust (Royal Preston Hospital)
    Preston, United Kingdom
    Recruiting
  • The Shrewsbury & Telford Hospitals NHS Trust (Royal Shrewsbury Hospital)
    Shrewsbury, United Kingdom
    Recruiting
    • Sanjeev Deshpandar, MD · Contact
  • University Hospital Southampton NHS Foundation Trust (Southampton General Hospital)
    Southampton, United Kingdom
    Recruiting
  • Betsi Cadwaladr University Health Board (Glan Cwyd Hospital)
    Wales, United Kingdom
    Recruiting
  • Walsall Healthcare NHS Trust (Walsall Manor Hospital)
    Walsall, United Kingdom
    Recruiting
  • West Hertfordshire Hospitals NHS Trust (Watford General Hospital)
    Watford, United Kingdom
    Recruiting
  • Royal Wolverhampton NHS Trust (New Cross Hospital)
    Wolverhampton, United Kingdom
    Recruiting
08

References and documents

Publications

  • Battersby C, Longford N, Mandalia S, Costeloe K, Modi N; UK Neonatal Collaborative Necrotising Enterocolitis (UKNC-NEC) study group. Incidence and enteral feed antecedents of severe neonatal necrotising enterocolitis across neonatal networks in England, 2012-13: a whole-population surveillance study. Lancet Gastroenterol Hepatol. 2017 Jan;2(1):43-51. doi: 10.1016/S2468-1253(16)30117-0. Epub 2016 Nov 8. PubMed 28404014 ↗
  • Duro D, Kalish LA, Johnston P, Jaksic T, McCarthy M, Martin C, Dunn JC, Brandt M, Nobuhara KK, Sylvester KG, Moss RL, Duggan C. Risk factors for intestinal failure in infants with necrotizing enterocolitis: a Glaser Pediatric Research Network study. J Pediatr. 2010 Aug;157(2):203-208.e1. doi: 10.1016/j.jpeds.2010.02.023. Epub 2010 May 6. PubMed 20447649 ↗
  • Hintz SR, Kendrick DE, Stoll BJ, Vohr BR, Fanaroff AA, Donovan EF, Poole WK, Blakely ML, Wright L, Higgins R; NICHD Neonatal Research Network. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics. 2005 Mar;115(3):696-703. doi: 10.1542/peds.2004-0569. PubMed 15741374 ↗
  • Rees CM, Pierro A, Eaton S. Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2007 May;92(3):F193-8. doi: 10.1136/adc.2006.099929. Epub 2006 Sep 19. PubMed 16984980 ↗
  • Duley L, Uhm S, Oliver S; Preterm Birth Priority Setting Partnership Steering Group. Top 15 UK research priorities for preterm birth. Lancet. 2014 Jun 14;383(9934):2041-2042. doi: 10.1016/S0140-6736(14)60989-2. No abstract available. PubMed 24931684 ↗
  • Seges RA, Kenny A, Bird GW, Wingham J, Baals H, Stauffer UG. Pediatric surgical patients with severe anaerobic infection: report of 16 T-antigen positive cases and possible hazards of blood transfusion. J Pediatr Surg. 1981 Dec;16(6):905-10. doi: 10.1016/s0022-3468(81)80844-5. PubMed 6279816 ↗
  • Stritzke AI, Smyth J, Synnes A, Lee SK, Shah PS. Transfusion-associated necrotising enterocolitis in neonates. Arch Dis Child Fetal Neonatal Ed. 2013 Jan;98(1):F10-4. doi: 10.1136/fetalneonatal-2011-301282. Epub 2012 Mar 23. PubMed 22447991 ↗
  • Blau J, Calo JM, Dozor D, Sutton M, Alpan G, La Gamma EF. Transfusion-related acute gut injury: necrotizing enterocolitis in very low birth weight neonates after packed red blood cell transfusion. J Pediatr. 2011 Mar;158(3):403-9. doi: 10.1016/j.jpeds.2010.09.015. Epub 2010 Nov 10. PubMed 21067771 ↗
  • Mally P, Golombek SG, Mishra R, Nigam S, Mohandas K, Depalhma H, LaGamma EF. Association of necrotizing enterocolitis with elective packed red blood cell transfusions in stable, growing, premature neonates. Am J Perinatol. 2006 Nov;23(8):451-8. doi: 10.1055/s-2006-951300. Epub 2006 Sep 28. PubMed 17009195 ↗
  • Cunningham KE, Okolo FC, Baker R, Mollen KP, Good M. Red blood cell transfusion in premature infants leads to worse necrotizing enterocolitis outcomes. J Surg Res. 2017 Jun 1;213:158-165. doi: 10.1016/j.jss.2017.02.029. Epub 2017 Feb 28. PubMed 28601308 ↗
  • Keir AK, Yang J, Harrison A, Pelausa E, Shah PS; Canadian Neonatal Network. Temporal changes in blood product usage in preterm neonates born at less than 30 weeks' gestation in Canada. Transfusion. 2015 Jun;55(6):1340-6. doi: 10.1111/trf.12998. Epub 2015 Feb 5. PubMed 25652740 ↗
  • Kirpalani H, Whyte RK, Andersen C, Asztalos EV, Heddle N, Blajchman MA, Peliowski A, Rios A, LaCorte M, Connelly R, Barrington K, Roberts RS. The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. J Pediatr. 2006 Sep;149(3):301-307. doi: 10.1016/j.jpeds.2006.05.011. PubMed 16939737 ↗
  • Jasani B, Rao S, Patole S. Withholding Feeds and Transfusion-Associated Necrotizing Enterocolitis in Preterm Infants: A Systematic Review. Adv Nutr. 2017 Sep 15;8(5):764-769. doi: 10.3945/an.117.015818. Print 2017 Sep. PubMed 28916576 ↗
  • Sahin S, Gozde Kanmaz Kutman H, Bozkurt O, Yavanoglu Atay F, Emre Canpolat F, Uras N, Suna Oguz S, Underwood MA. Effect of withholding feeds on transfusion-related acute gut injury in preterm infants: a pilot randomized controlled trial. J Matern Fetal Neonatal Med. 2020 Dec;33(24):4139-4144. doi: 10.1080/14767058.2019.1597844. Epub 2019 Mar 28. PubMed 30890001 ↗
  • Neu J. Necrotizing enterocolitis: the search for a unifying pathogenic theory leading to prevention. Pediatr Clin North Am. 1996 Apr;43(2):409-32. doi: 10.1016/s0031-3955(05)70413-2. PubMed 8614608 ↗
  • Battersby C, Longford N, Costeloe K, Modi N; UK Neonatal Collaborative Necrotising Enterocolitis Study Group. Development of a Gestational Age-Specific Case Definition for Neonatal Necrotizing Enterocolitis. JAMA Pediatr. 2017 Mar 1;171(3):256-263. doi: 10.1001/jamapediatrics.2016.3633. PubMed 28046187 ↗

Individual participant data

Plan to share: Yes — De-identified participant data, the data dictionary, statistical code and other study materials.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Analytic code

Time frame: Made available following publication of the primary results manuscript (for 10 years).

Access criteria: Access will be considered by the trial team and sponsors, in accordance with participant confidentiality, consent permissions, ethics approvals and applicable data protection requirements.

09

Updates

1 registry update since Sep 25, 2026
Minor edits
Nothing that changes what the study is or who can join. Edited: identifiers and data sharing statement
1 update, last Sep 29, 2026
Show all 1 update
  1. Sep 29, 2026
    Minor edits only
    + 2 other changes: identifiers and data sharing statement

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT05213806
Lead sponsor
IWK Health Centre
Collaborators
Canadian Institutes of Health Research (CIHR), Imperial College London
Responsible party
Dr. Balpreet Singh (Principal Investigator, IWK Health Centre) — Principal investigator
First posted
Jan 28, 2022
Start date
Jan 28, 2022
Primary completion
Mar 31, 2027 (estimated)
Completion
Mar 31, 2027 (estimated)
Last update
Sep 29, 2026

Study contacts

Cari-Lee Carnell
Contact
cari-lee.carnell@iwk.nshealth.ca
9024706630
Tara Hatfield
Contact
tara.hatfield@iwk.nshealth.ca
9024706630
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

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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