Clinical trial NCT01686477: PREterM FOrmula Or Donor Breast Milk for Premature Babies
Official title: Preterm Formula or Donor Breast Milk to Make up Any Shortfall in Mother's Own Milk
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Adiposity
Insulin Resistance
Metabolomic Profile
microRNA Profile
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2012-09-18
Enrollment: 103
Sex: ALL
Minimum age (years): 25
Maximum age (years): 31
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Total Body Adiposity
timeFrame: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
Secondary outcomes:
measure: Consent Rate for Feeding Intervention (Opt Out Approach)
timeFrame: Up to the first 48hrs of life
measure: Parental Withdrawal From Feed Intervention
timeFrame: From birth to 35 weeks post menstrual age
measure: Parental Withdrawal Rate From Feed Intervention by Arm
timeFrame: From birth to 35 weeks post menstrual age
measure: Clinician Refusal to Randomise
timeFrame: Up to the first 48hrs of life.
measure: Safety Criteria Threshold
timeFrame: Birth to 35 weeks post menstrual age
measure: Weight at Term
timeFrame: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
measure: Length at Term
timeFrame: Term corrected age (as close as possible to due date)
measure: Head Circumference at Term
timeFrame: Term corrected age (as close as possible to due date)
measure: Regional Adiposity, as Measured by Whole Body MRI, at Term.
timeFrame: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
measure: Non Adipose Tissue, as Measured by Whole Body MRI, at Term
timeFrame: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
measure: Weight at Term Plus 6 Weeks
timeFrame: Term plus 6 weeks corrected age
measure: Length at Term Plus 6 Weeks
timeFrame: Term plus 6 weeks
measure: Head Circumference at Term Plus 6 Weeks
timeFrame: Term plus 6 weeks
measure: Total Body Adiposity at Term Plus 6 Weeks
timeFrame: Term plus 6 weeks
measure: Regional Adiposity, as Measured by Whole Body MRI at Term Plus 6 Weeks
timeFrame: Term plus 6 weeks corrected age
measure: Non Adipose Tissue, as Measured by Whole Body MRI at Term Plus 6 Weeks
timeFrame: Term plus 6 weeks corrected age
measure: Blood Quantitative Insulin Sensitivity Check Index (QUICKI)
timeFrame: Measured at 35 weeks Post Menstrual Age
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital Neonatal Unit
Study officials:
affiliation: Imperial College London
name: Neena Modi, MBChB
role: PRINCIPAL_INVESTIGATOR
References: