PREterM FOrmula Or Donor Breast Milk for Premature Babies

Not Applicable

Completed

• Conditions: Insulin Resistance; Metabolomic Profile; Adiposity; microRNA Profile
• Interventions: Other: Unfortified 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; Other: Fortified Human donor Milk used to make up any shortfall in mother's own milk

• Registration Number: NCT01686477
• Lead Sponsor: Imperial College London

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2012-08-07
• Study First Submitted QC: 2012-09-12
• Study First Posted: 2012-09-18
• Study Start: 2013-04-02
• Primary Completion: 2020-10-01
• Study Completion: 2020-10-01
• Results First Submitted: 2021-09-30
• Status Verified: 2023-10
• Results First Submitted QC: 2023-10-31
• Last Update Submitted: 2023-10-31
• Results First Posted: 2024-04-26
• Last Update Posted: 2024-04-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 103

Inclusion Criteria

• Preterm infants born between 25+0 to 31+6 weeks gestational age
• Written informed consent from parents

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Exclusion Criteria

• Major congenital or life threatening abnormalities or congenital abnormalities that preclude early milk feeding
• Inability to randomise infant within 48 hours

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Unfortified Human Donor Milk	Unfortified Human donor Milk used to make up any shortfall in mother's own milk	Used to make up any shortfall in mother's own milk
Preterm Formula	Preterm Formula used when there is a shortfall in mother's own milk	Used to make up any shortfall in mother's own milk
Fortified Human Donor Milk	Fortified Human donor Milk used to make up any shortfall in mother's own milk	Used to make up any shortfall in mother's own milk

Primary Outcome Measures

Name	Time	Method
Total Body Adiposity	Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)	As measured by whole body Magnetic Resonance Imaging (MRI). MR images were acquired using a rapid T1-weighted spin-echo sequence allowing whole body imaging. Images obtained give good contrast between adipose tissue and other tissues, and allows direct measurement of adipose compartment volumes, whole body adipose volume being the sum of these compartments. 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).

Secondary Outcome Measures

Name	Time	Method
Head Circumference at Term Plus 6 Weeks	Term plus 6 weeks	Head circumference at Term plus 6 weeks by feed intervention arm
Non Adipose Tissue, as Measured by Whole Body MRI, at Term	Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)	Non adipose tissue, as measured by whole body Magnetic Resonance Imaging (MRI) at term. MR images were acquired using a rapid T1-weighted spin-echo sequence allowing whole body imaging. Images obtained give good contrast between adipose tissue and other tissues, and allows direct measurement of adipose compartment volumes, whole body adipose tissue volume being the sum of these adipose compartment volumes. This volume may be converted to adipose tissue mass on the assumption that the density of adipose tissue is 0.9 g/cm³. Non adipose tissue mass reported here is weight (g) minus whole body adipose mass (g)
Consent Rate for Feeding Intervention (Opt Out Approach)	Up to the first 48hrs of life	Consent rate for feeding intervention of number of parents of eligible infants approached and study discussed with (opt out approach)
Parental Withdrawal From Feed Intervention	From birth to 35 weeks post menstrual age	Parental withdrawal rate from feed intervention
Weight at Term	Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)	Weight at term by feed intervention arm
Regional Adiposity, as Measured by Whole Body MRI, at Term.	Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)	Internal Abdominal Adipose Tissue at Term reported here. As measured by whole body Magnetic Resonance Imaging (MRI). MR images were acquired using a rapid T1-weighted spin-echo sequence allowing whole body imaging. Images obtained give good contrast between adipose tissue and other tissues, and allows direct measurement of adipose compartment volumes. These adipose compartments are defined as superficial subcutaneous, deep subcutaneous, and internal. Each of these three compartments are further subdivided into abdominal and non-abdominal.
Parental Withdrawal Rate From Feed Intervention by Arm	From birth to 35 weeks post menstrual age	Parental withdrawal rate from feed intervention by feed intervention arm
Safety Criteria Threshold	Birth to 35 weeks post menstrual age	Number of infants who met the weight gain safety criteria. Safety criteria defined by slow growth were based on the UK Neonatal and Infant Close Monitoring growth chart 2009: if after two weeks of reaching a milk volume of 120ml/kg/d, the infant showed a 3 marked centile downward crossing (equating to approximately a 1.4-2.0 z-score change from birthweight) fortification or formula was commenced
Head Circumference at Term	Term corrected age (as close as possible to due date)	Head circumference at term by feed intervention arm
Weight at Term Plus 6 Weeks	Term plus 6 weeks corrected age	Weight at Term plus 6 weeks by feed intervention arm
Length at Term Plus 6 Weeks	Term plus 6 weeks	Length at Term plus 6 weeks by feed intervention group
Total Body Adiposity at Term Plus 6 Weeks	Term plus 6 weeks	As measured by whole body Magnetic Resonance Imaging (MRI). MR images were acquired using a rapid T1-weighted spin-echo sequence allowing whole body imaging. Images obtained give good contrast between adipose tissue and other tissues, and allows direct measurement of adipose compartment volumes, total body adipose tissue volume being the sum of all these compartment volumes.
Clinician Refusal to Randomise	Up to the first 48hrs of life.	Attending clinician refusal to randomise eligible infant into feeding intervention
Length at Term	Term corrected age (as close as possible to due date)	Length at term by feed intervention arm
Regional Adiposity, as Measured by Whole Body MRI at Term Plus 6 Weeks	Term plus 6 weeks corrected age	Regional adiposity, as measured by whole body MRI at Term plus 6 weeks, Internal Abdominal Adipose Tissue reported here. As measured by whole body Magnetic Resonance Imaging (MRI). MR images were acquired using a rapid T1-weighted spin-echo sequence allowing whole body imaging. Images obtained give good contrast between adipose tissue and other tissues, and allows direct measurement of adipose compartment volumes. These adipose compartments are defined as superficial subcutaneous, deep subcutaneous, and internal. Each of these three compartments are further subdivided into abdominal and non-abdominal.
Non Adipose Tissue, as Measured by Whole Body MRI at Term Plus 6 Weeks	Term plus 6 weeks corrected age	Non adipose tissue, as measured by whole body MRI, at Term plus 6 weeks. As measured by whole body Magnetic Resonance Imaging (MRI). MR images were acquired using a rapid T1-weighted spin-echo sequence allowing whole body imaging. Images obtained give good contrast between adipose tissue and other tissues, and allows direct measurement of adipose compartment volumes, whole body adipose tissue volume being the sum of these adipose compartment volumes. This volume may be converted to adipose tissue mass on the assumption that the density of adipose tissue is 0.9 g/cm³. Non adipose tissue mass reported here is weight (g) minus whole body adipose mass (g)
Blood Quantitative Insulin Sensitivity Check Index (QUICKI)	Measured at 35 weeks Post Menstrual Age	The quantitative insulin sensitivity check index (QUICKI) is derived using the inverse of the sum of the logarithms of the fasting insulin and fasting glucose: 1 / (log(fasting insulin μU/mL) + log(fasting glucose mg/dL)). This index correlates well with glucose clamp studies and is useful for measuring insulin sensitivity (IS), which is the inverse of insulin resistance (IR). The higher the value of QUICKI, the higher the measure of insulin sensitivity. Reference ranges for adults, and less so preterm newborns, have not been fully established; values of 0.3 in adults or below are typically associated with insulin resistance or diabetes. In a large cohort of 115 term, normoweight newborns at birth (Gesteiro E. Eur J Pediatr. 2009 Mar;168(3):281-8), mean (95% confidence interval) QUICKI was 0.45 (0.43-0.48)

Trial Locations

Locations (1)

Chelsea and Westminster Hospital Neonatal Unit; 🇬🇧 London, United Kingdom