PREterM FOrmula Or Donor Breast Milk for Premature Babies

Study Overview
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Brief Summary
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In order to address this crucial question, central to preterm newborn care, a multicentre United Kingdom (UK) -wide study randomising 4000 preterm babies would be necessary to achieve sufficient power to evaluate the impact on the short-term outcomes necrotising enterocolitis and bloodstream infection, and establish cohorts large enough to address long-term metabolic (such as obesity, type 2 diabetes), cardiovascular (such as blood pressure) and developmental outcomes. This pilot trial will evaluate the practicability and feasibility of such a large multicentre UK randomised controlled trial. In addition to evaluating feasibility and to ensure maximal use of resources allocated, this study will also assess outcomes that are indicative of long term metabolic health.

Detailed Description
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Mother's Own Milk (MOM) is recommended for preterm babies. However, on average, mothers giving birth preterm are able to provide less than half their baby's milk requirements. Standard clinical practice is to make up any shortfall in MOM with either pasteurised Human Donor Milk (HDM) or Preterm Formula (PTF). Which option is more beneficial to clinical outcomes is unknown. Pasteurisation reduces or destroys many biologically active components and HDM, unlike PTF, is very variable in composition. Clinicians who use HDM do so primarily in the hope that despite pasteurisation it will reduce bloodstream infection and necrotising enterocolitis, a serious, devastating inflammatory disease characterised by bowel death and multisystem failure. These are two of the most feared conditions in newborn medicine as described above. Landmark nutritional trials in the early 1980's suggest positive effects of human milk on insulin sensitivity, and other metabolic outcomes. Clinicians who prefer PTF believe it benefits growth, including brain growth, and improves neurodevelopmental outcome. Neonates born below 32 weeks gestational age will be randomised to receive fortified HDM, unfortified HDM, or PTF to make up any shortfall in MOM until 35 weeks postmenstrual age with a sample size of 22 in each group. The trial is designed to reflect current preterm feeding practice. The trial will take place in neonatal units in London and parent consent obtained within 48hr of birth. Permission will be sought for long term follow up, initially from parents (later from children themselves). Outcomes will be body composition using magnetic resonance imaging and other imaging techniques. This pilot study will specifically assess feasibility by testing 1) provision of HDM by Human Milk Banks in London 2) acceptability to parents and clinicians using feedback on trial design 3) recruitment to target and 4) retrieval of clinical data for all recruited babies form the National Neonatal Database.

Official Title
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Preterm Formula or Donor Breast Milk to Make up Any Shortfall in Mother's Own Milk

Conditions
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Adiposity, Insulin Resistance, Metabolomic Profile, microRNA Profile

Intervention / Treatment
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* Other: Unfortified Human donor Milk used to make up any shortfall in mother's own milk
* Other: Fortified Human donor Milk used to make up any shortfall in mother's own milk
* Other: Preterm Formula used when there is a shortfall in mother's own milk


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm infants born between 25+0 to 31+6 weeks gestational age Written informed consent from parents Exclusion Criteria: Major congenital or life threatening abnormalities or congenital abnormalities that preclude early milk feeding Inability to randomise infant within 48 hours

Ages Eligible for Study
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Minimum Age: 25 Weeks
Maximum Age: 31 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Unfortified Human Donor Milk<br>Used to make up any shortfall in mother's own milk | Other: Unfortified Human donor Milk used to make up any shortfall in mother's own milk<br> <br> |
| Active Comparator: Fortified Human Donor Milk<br>Used to make up any shortfall in mother's own milk | Other: Fortified Human donor Milk used to make up any shortfall in mother's own milk<br> <br> |
| Active Comparator: Preterm Formula<br>Used to make up any shortfall in mother's own milk | Other: Preterm Formula used when there is a shortfall in mother's own milk<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Body Adiposity | As measured by whole body Magnetic Resonance Imaging (MRI). The time taken to reach term age equivalent will vary depending on the birth gestational age of the infant. The range will be 8-15 weeks (representing gestational birth age from 25-32 weeks). | Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility data | test the acceptability of the trial design with parents and clinicians test that recruitment to target is achievable, estimate consent and dropout rates estimate the trial requirement for HDM from National Health Service (NHS) Human Milk Banks test that clinical outcome data can be retrieved from operational NHS electronic records, thus minimising the burden of data capture and facilitating the use of linked NHS records to achieve long-term follow-up at low cost. | 18 months |