A UK-wide study to find out which routine top-up feeds for extremely preterm babies when there is insufficient own mother’s milk, reduce the likelihood of necrotising enterocolitis and improve survival and brain development
| ISRCTN | ISRCTN10443084 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10443084 |
| Integrated Research Application System (IRAS) | 337660 |
| Central Portfolio Management System (CPMS) | 59907 |
| National Institute for Health and Care Research (NIHR) | NIHR163188 |
| Sponsor | Imperial College London |
| Funder | National Institute for Health and Care Research |
- Submission date
- 15/12/2025
- Registration date
- 13/01/2026
- Last edited
- 13/01/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Neonatal Diseases
Plain English summary of protocol
Background and study aims
This study will address two uncertainties in the care of babies born less that 29 weeks gestation. First whether pasteurised human donor milk or preterm formula, when used to supplement insufficient availability of milk from a baby's own mother, and second whether routine versus no routine fortification of human milk feeds, affects survival to 34 weeks postmenstrual age without requiring surgery for necrotising enterocolitis. Necrotising enterocolitis is an acquired inflammation of the intestinal tract and a major cause of death and long-term impairment in preterm babies. We will also evaluate a range of important secondary outcomes and associated hospital costs. The study additionally includes an embedded sub-study that will use magnetic resonance imaging (MRI) and serial stool sampling to determine whether donor milk and formula have different effects on development.
Who can participate?
Preterm babies born below 29 weeks gestation
What does the study involve?
After consent, participants will be randomised. Randomisation 1 to donor milk or formula will occur when the clinician decides a supplemental feed is required because the volume of own mother’s milk is insufficient. Randomisation 2 to routine fortification or no routine fortification will occur when the baby is receiving between 60-120 ml/kg/day of human milk feeds (own mother’s milk and/or donor milk). There will be no research-related procedures except for infants participating in the sub-study, who will be invited for a brain MRI at at term equivalent age (38-42 weeks) plus serial stool sample collection. After the infant is discharged, there are no research-related follow-up visits. Age 2-year cognitive and language outcomes will be obtained as a component of routine clinical care. A digital option for completion will be provided.
What are the possible benefits and risks of participating?
The decision of which option each baby will receive will be made fairly and equally by randomisation. All feeding options used in this study are already used in UK hospitals.
If your baby takes part, they may not directly benefit themselves, but will help improve the care of preterm babies in the future. However, participants in randomised studies like COLLABORATE often have better outcomes than equivalent patients who do not take part; this is called “inclusion benefit”.
Where is the study run from?
Imperial College London (UK)
When is the study starting and how long is it expected to run for?
Recruitment is planned from December 2025 to November 2027. The study will complete in May 2030.
Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK)
Who is the main contact?
1. Trial Manager, collaborate@imperial.ac.uk
2. Prof. Neena Modi, n.modi@imperial.ac.uk
Contact information
Principal investigator
Imperial College London
Section of Neonatal Medicine
Chelsea and Westminster Hospital Campus
School of Public Health
369 Fulham Road
London
SW10 9NH
United Kingdom
 ORCID ID |
0000-0002-2093-0681 |
|---|---|
| n.modi@imperial.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Adaptive two-randomization controlled trial |
| Secondary study design | Randomised controlled trial |
| Scientific title | An efficient, UK-wide, real-world-data-enabled, adaptive, 2-randomisation, controlled trial to determine clinical efficacy, effect size, and safety of widely used enteral feeds in reducing necrotising enterocolitis, mortality, and cognitive impairment in preterm babies born below 29 weeks gestation |
| Study acronym | COLLABORATE |
| Study objectives | Primary objectives: 1. To assess, in babies born <29 weeks gestation, the efficacy of pHDM compared with Preterm Formula when used as a supplement should there be insufficient milk from their own mother (Own Mother's Milk) on “survival to 34 weeks postmenstrual age without surgical NEC” 2. To assess, in babies born <29 weeks gestation, if routine cow-milk-based protein-carbohydrate fortification of human milk feeds (Own Mother’s Milk and pHDM) compared with no routine fortification, affects “survival to 34 weeks postmenstrual age without surgical NEC” Secondary objectives: 1. To assess the efficacy of pHDM compared with Preterm Formula on language and cognitive development at age 2-years, and other outcomes in babies born <29 weeks gestation, when used as a supplement should there be insufficient milk from their own mother (Own Mother's Milk) 2. To assess if routine cow-milk-based protein-carbohydrate fortification of human milk feeds (Own Mother’s Milk and pHDM) in babies born <29 weeks gestation affects language and cognitive development at age 2-years, and other outcomes Tertiary objectives: 1. To determine if pHDM and Preterm Formula exert different effects on neurodevelopment through the mechanism of altered cerebral white matter microstructure. 2. To establish if the additional cost of pHDM to the NHS is justified through a reduction in NEC 3. To establish if the additional cost of fortifier generates savings through improved survival to age 2 years corrected for prematurity without moderate-severe cognitive-language impairment 4. To collect and store faecal samples from participants recruited in Edinburgh who are enrolled in randomisation 1, for future mechanistic studies, subject to funding |
| Ethics approval(s) | Approved 29/10/2025, London - Bloomsbury Research Ethics Committee (Health Research Authority, 2 Redman Place, Stratford, London, E20 1JQ, UK; bloomsbury.rec@hra.nhs.uk), ref: 25/LO/0697 |
| Health condition(s) or problem(s) studied | Necrotising enterocolitis, mortality, and cognitive impairment in preterm babies born below 29 weeks gestation |
| Intervention | All interventions and comparators being used in the COLLABORATE trial are currently used as part of routine care in hospitals; no experimental treatments are being tested. The intervention for randomisation 1 is pasteurised Human Donor Milk (pHDM) when a supplement is needed should there be insufficient milk from their own mother (Own Mother's Milk). Hospitals obtain pHDM from one of 15 human milk banks in the country that operate on a charitable or not-for-profit basis. The intervention for randomisation 2 is multicomponent fortifier, a commercial product available as a powder added to human milk (Own Mother’s Milk and pHDM), that is prepared from cow milk and contains protein, carbohydrate, minerals, vitamins, and trace elements. Fortifiers used in the UK are standard hospital stock. The comparator for randomisation 1 is preterm formula (standard hospital stock) when a supplement is needed should there be insufficient milk from their own mother (Own Mother's Milk). |
| Intervention type | Other |
| Primary outcome measure(s) |
Survival at 34 weeks postmenstrual age without surgical NEC, assessed from data held in the UK National Neonatal Research Database |
| Key secondary outcome measure(s) |
All outcomes are assessed from data held in the UK National Neonatal Research Database unless otherwise stated. |
| Completion date | 30/01/2030 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Sex | All |
| Target sample size at registration | 3252 |
| Key inclusion criteria | Randomisation 1: 1. Born <29 weeks gestation 2. No condition precluding enteral feeding 3. Maternal intention to express breast milk 4. The parent has provided verbal consent for the baby to participate in the trial Randomisation 2: 1. Born <29 weeks gestation 2. No condition precluding enteral feeding 3. Maternal intention to express breast milk 4. The parent has provided verbal consent for the baby to participate in the trial Mechanistic study: 1. Participants in randomisation 1 recruited at the Royal Infirmary of Edinburgh 2. Written informed consent for the mechanistic study |
| Key exclusion criteria | Randomisation 1: 1. Baby has already received pHDM, Preterm Formula Randomisation 2: 1. Baby has already received Fortifier Mechanistic study: 1. Infants with congenital anomalies: structural or functional anomalies (e.g., metabolic disorders) that occur during intrauterine life and can be identified prenatally, at birth or later in life (WHO definition) 2. Infants with a contraindication to MRI at 3 Tesla |
| Date of first enrolment | 19/01/2026 |
| Date of final enrolment | 30/11/2027 |
Locations
Countries of recruitment
- United Kingdom
- England
- Northern Ireland
- Scotland
- Wales
Study participating centres
369 Fulham Road
London
SW10 9NH
England
2-4 Waterloo Place
Edinburgh
EH1 3EG
Scotland
Hills Road
Cambridge
CB2 0QQ
England
Uttoxeter Road
Derby
DE22 3NE
England
Shrewsbury
SY3 8XQ
England
A Floor - Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
England
43 Bush Road
Antrim
BT41 2QB
Northern Ireland
Upper Newtownards Road
Dundonald
Belfast
BT16 1RH
Northern Ireland
Altnagelvin Area Hospital Site
Glenshane Road
Londonderry
BT47 6SB
Northern Ireland
Craigavon Area Hospital
68 Lurgan Road, Portadown
Craigavon
BT63 5QQ
Northern Ireland
Infirmary Square
Leicester
LE1 5WW
England
Ethelbert Road
Canterbury
CT1 3NG
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The anonymised dataset will be available as de-identified data upon request from the Chief Investigator Professor Neena Modi (n.modi@imperial.ac.uk) beginning 12 months and ending 5 years after the primary publication and pre-planned secondary analysis, following approval of a methodologically sound proposal and a signed data sharing agreement. The parent information leaflet provided to parents prior to them verbally consenting to the study explains data sharing procedures and potential future uses of study data. |
Editorial Notes
15/12/2025: Study's existence confirmed by the NIHR.
