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Completed

NCT Number: NCT01686477

PREterM FOrmula Or Donor Breast Milk for Premature Babies

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.

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Key information

Age range

25 week–31 week

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Chelsea and Westminster Hospital Neonatal Unit

London, SW10 9NH, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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

Other

Primary outcomes

  1. Total Body Adiposity

    Time frame: 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 outcomes

  1. Consent Rate for Feeding Intervention (Opt Out Approach)

    Time frame: 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)

  2. Parental Withdrawal From Feed Intervention

    Time frame: From birth to 35 weeks post menstrual age

    Parental withdrawal rate from feed intervention

  3. Parental Withdrawal Rate From Feed Intervention by Arm

    Time frame: From birth to 35 weeks post menstrual age

    Parental withdrawal rate from feed intervention by feed intervention arm

  4. Clinician Refusal to Randomise

    Time frame: Up to the first 48hrs of life.

    Attending clinician refusal to randomise eligible infant into feeding intervention

  5. Safety Criteria Threshold

    Time frame: 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

  6. Weight at Term

    Time frame: 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

  7. Length at Term

    Time frame: Term corrected age (as close as possible to due date)

    Length at term by feed intervention arm

  8. Head Circumference at Term

    Time frame: Term corrected age (as close as possible to due date)

    Head circumference at term by feed intervention arm

  9. Regional Adiposity, as Measured by Whole Body MRI, at Term.

    Time frame: 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.

  10. Non Adipose Tissue, as Measured by Whole Body MRI, at Term

    Time frame: 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)

  11. Weight at Term Plus 6 Weeks

    Time frame: Term plus 6 weeks corrected age

    Weight at Term plus 6 weeks by feed intervention arm

  12. Length at Term Plus 6 Weeks

    Time frame: Term plus 6 weeks

    Length at Term plus 6 weeks by feed intervention group

  13. Head Circumference at Term Plus 6 Weeks

    Time frame: Term plus 6 weeks

    Head circumference at Term plus 6 weeks by feed intervention arm

  14. Total Body Adiposity at Term Plus 6 Weeks

    Time frame: 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.

  15. Regional Adiposity, as Measured by Whole Body MRI at Term Plus 6 Weeks

    Time frame: 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.

  16. Non Adipose Tissue, as Measured by Whole Body MRI at Term Plus 6 Weeks

    Time frame: 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)

  17. Blood Quantitative Insulin Sensitivity Check Index (QUICKI)

    Time frame: 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)

Sponsors and collaborators

Lead sponsor

Imperial College London

Other

Registry information

Official study title

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

Acronym: PREMFOOD

Important dates

Study start
2013
Primary completion
2020
Study completion
2020
First posted
Sep 18, 2012
Registry last updated
Apr 26, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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