Trial Outcomes & Findings for PREterM FOrmula Or Donor Breast Milk for Premature Babies (NCT NCT01686477)

NCT ID: NCT01686477

Last Updated: 2024-04-26

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 103 participants
• Primary outcome timeframe: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
• Results posted on: 2024-04-26

Participant Flow

Participant milestones

Measure	Unfortified Human Donor Milk Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Feeding Intervention STARTED	35	34	34
Feeding Intervention COMPLETED	32	25	31
Feeding Intervention NOT COMPLETED	3	9	3
Primary Outcome Term Scan STARTED	30	25	30
Primary Outcome Term Scan COMPLETED	21	19	24
Primary Outcome Term Scan NOT COMPLETED	9	6	6
Term Plus 6 Week Scan (End of Study) STARTED	21	19	24
Term Plus 6 Week Scan (End of Study) COMPLETED	14	5	19
Term Plus 6 Week Scan (End of Study) NOT COMPLETED	7	14	5

Reasons for withdrawal

Measure	Unfortified Human Donor Milk Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Feeding Intervention Death	1	0	1
Feeding Intervention Withdrawal by Subject	0	6	0
Feeding Intervention Physician Decision	1	2	0
Feeding Intervention Met pre-defined safety threshold	1	0	1
Feeding Intervention Transfer to a non-participating hospital	0	1	1
Primary Outcome Term Scan Withdrawal by Subject	6	5	5
Primary Outcome Term Scan Lost to Follow-up	1	1	1
Primary Outcome Term Scan Scanner unavailable to measure primary outcome	2	0	0
Term Plus 6 Week Scan (End of Study) Withdrawal by Subject	7	12	5
Term Plus 6 Week Scan (End of Study) Lost to Follow-up	0	2	0

Baseline Characteristics

PREterM FOrmula Or Donor Breast Milk for Premature Babies

Baseline characteristics by cohort

Measure	Unfortified Human Donor Milk n=35 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in mother's own milk	Fortified Human Donor Milk n=34 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in mother's own milk	Preterm Formula n=34 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk	Total n=103 Participants Total of all reporting groups
Age, Continuous	29.4 Completed gestational weeks STANDARD_DEVIATION 2.2 • n=5 Participants	29.6 Completed gestational weeks STANDARD_DEVIATION 2.0 • n=7 Participants	29.7 Completed gestational weeks STANDARD_DEVIATION 1.7 • n=5 Participants	29.5 Completed gestational weeks STANDARD_DEVIATION 1.9 • n=4 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	13 Participants n=7 Participants	15 Participants n=5 Participants	43 Participants n=4 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	21 Participants n=7 Participants	19 Participants n=5 Participants	60 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants n=5 Participants	34 Participants n=7 Participants	34 Participants n=5 Participants	103 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United Kingdom	35 participants n=5 Participants	34 participants n=7 Participants	34 participants n=5 Participants	103 participants n=4 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	Unfortified Human Donor Milk n=21 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=19 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=24 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Total Body Adiposity	0.893 Litres Standard Deviation 0.38	0.863 Litres Standard Deviation 0.26	0.809 Litres Standard Deviation 0.25

SECONDARY outcome

Timeframe: Up to the first 48hrs of life

Population: Parents of 165 eligible infants for which the study was discussed with and opportunity offered to opt-out from randomisation to feed intervention

Consent rate for feeding intervention of number of parents of eligible infants approached and study discussed with (opt out approach)

Outcome measures

Measure	Unfortified Human Donor Milk n=165 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Consent Rate for Feeding Intervention (Opt Out Approach)	103 Participants	—	—

SECONDARY outcome

Timeframe: From birth to 35 weeks post menstrual age

Population: All participants

Parental withdrawal rate from feed intervention

Outcome measures

Measure	Unfortified Human Donor Milk n=103 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Parental Withdrawal From Feed Intervention	6 Participants	—	—

SECONDARY outcome

Timeframe: From birth to 35 weeks post menstrual age

Population: Parental withdrawal rate from feed intervention by arm

Parental withdrawal rate from feed intervention by feed intervention arm

Outcome measures

Measure	Unfortified Human Donor Milk n=35 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=34 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=34 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Parental Withdrawal Rate From Feed Intervention by Arm	0 Participants	6 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to the first 48hrs of life.

Population: All eligible participants who consented for feed intervention who were then not randomised due to clinician refusal

Attending clinician refusal to randomise eligible infant into feeding intervention

Outcome measures

Measure	Unfortified Human Donor Milk n=103 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Clinician Refusal to Randomise	0 Participants	—	—

SECONDARY outcome

Timeframe: Birth to 35 weeks post menstrual age

Population: All participants who consented for feed intervention

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

Outcome measures

Measure	Unfortified Human Donor Milk n=35 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=34 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=34 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Safety Criteria Threshold	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Unfortified Human Donor Milk n=21 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=19 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=24 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Weight at Term	3295 Grams Standard Deviation 798	3185 Grams Standard Deviation 678	3153 Grams Standard Deviation 656

SECONDARY outcome

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

Population: Feed intervention arm

Length at term by feed intervention arm

Outcome measures

Measure	Unfortified Human Donor Milk n=21 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=19 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=24 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Length at Term	50.0 Cm Standard Deviation 3.8	49.5 Cm Standard Deviation 3.0	49.6 Cm Standard Deviation 3.5

SECONDARY outcome

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

Population: Feed intervention arm

Head circumference at term by feed intervention arm

Outcome measures

Measure	Unfortified Human Donor Milk n=21 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=19 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=24 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Head Circumference at Term	35.9 Cm Standard Deviation 2.4	35.0 Cm Standard Deviation 1.9	35.4 Cm Standard Deviation 2.1

SECONDARY outcome

Timeframe: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)

Population: Feed intervention arm

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.

Outcome measures

Measure	Unfortified Human Donor Milk n=21 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=19 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=24 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Regional Adiposity, as Measured by Whole Body MRI, at Term.	0.043 Litres Standard Deviation 0.02	0.044 Litres Standard Deviation 0.02	0.040 Litres Standard Deviation 0.01

SECONDARY outcome

Timeframe: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)

Population: Feed intervention arm

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)

Outcome measures

Measure	Unfortified Human Donor Milk n=21 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=19 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=24 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Non Adipose Tissue, as Measured by Whole Body MRI, at Term	2511.79 Grams Standard Deviation 502.84	2385.74 Grams Standard Deviation 437.81	2424.70 Grams Standard Deviation 462.63

SECONDARY outcome

Timeframe: Term plus 6 weeks corrected age

Population: Feed intervention arm

Weight at Term plus 6 weeks by feed intervention arm

Outcome measures

Measure	Unfortified Human Donor Milk n=14 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=5 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=19 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Weight at Term Plus 6 Weeks	4564 Grams Standard Deviation 982	4594 Grams Standard Deviation 802	4590 Grams Standard Deviation 820

SECONDARY outcome

Timeframe: Term plus 6 weeks

Population: Feed intervention arm

Length at Term plus 6 weeks by feed intervention group

Outcome measures

Measure	Unfortified Human Donor Milk n=14 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=5 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=19 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Length at Term Plus 6 Weeks	55.70 Cm Standard Deviation 3.46	55.86 Cm Standard Deviation 2.87	55.98 Cm Standard Deviation 3.70

SECONDARY outcome

Timeframe: Term plus 6 weeks

Population: Feed intervention arm

Head circumference at Term plus 6 weeks by feed intervention arm

Outcome measures

Measure	Unfortified Human Donor Milk n=14 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=5 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=19 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Head Circumference at Term Plus 6 Weeks	38.76 Cm Standard Deviation 2.13	37.89 Cm Standard Deviation 1.97	38.91 Cm Standard Deviation 2.00

SECONDARY outcome

Timeframe: Term plus 6 weeks

Population: Feed Intervention Arm

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.

Outcome measures

Measure	Unfortified Human Donor Milk n=14 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=5 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=19 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Total Body Adiposity at Term Plus 6 Weeks	1.355 Litres Standard Deviation 0.486	1.474 Litres Standard Deviation 0.463	1.353 Litres Standard Deviation 0.284

SECONDARY outcome

Timeframe: Term plus 6 weeks corrected age

Population: Feed intervention arm

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.

Outcome measures

Measure	Unfortified Human Donor Milk n=14 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=5 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=19 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Regional Adiposity, as Measured by Whole Body MRI at Term Plus 6 Weeks	0.064 Litres Standard Deviation 0.023	0.061 Litres Standard Deviation 0.025	0.062 Litres Standard Deviation 0.018

SECONDARY outcome

Timeframe: Term plus 6 weeks corrected age

Population: Feed intervention arm

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)

Outcome measures

Measure	Unfortified Human Donor Milk n=14 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=5 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=19 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Non Adipose Tissue, as Measured by Whole Body MRI at Term Plus 6 Weeks	3263.98 Grams Standard Deviation 609.89	3208.10 Grams Standard Deviation 526.21	3364.38 Grams Standard Deviation 634.07

SECONDARY outcome

Timeframe: Measured at 35 weeks Post Menstrual Age

Population: Feed intervention arm

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)

Outcome measures

Measure	Unfortified Human Donor Milk n=13 Participants Used to make up any shortfall in mother's own milk Unfortified Human donor Milk used to make up any shortfall in unfortified mother's own milk	Fortified Human Donor Milk n=11 Participants Used to make up any shortfall in mother's own milk Fortified Human donor Milk used to make up any shortfall in fortified mother's own milk	Preterm Formula n=17 Participants Used to make up any shortfall in mother's own milk Preterm Formula used when there is a shortfall in mother's own milk
Blood Quantitative Insulin Sensitivity Check Index (QUICKI)	0.46 units on a scale Standard Deviation 0.09	0.42 units on a scale Standard Deviation 0.03	0.45 units on a scale Standard Deviation 0.09

Adverse Events

Unfortified Human Donor Milk

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Fortified Human Donor Milk

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Preterm Formula

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Luke Mills

ImperialC

Phone: +447989748017

Email: l.mills@imperial.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place