Donor milk for improved neurodevelopmental outcomes

ISRCTN	ISRCTN35317141
DOI	https://doi.org/10.1186/ISRCTN35317141
ClinicalTrials.gov (NCT)	NCT02759809
Protocol serial number	MP-102638
Sponsor	The Hospital for Sick Children
Funder	Canadian Institutes of Health Research (CIHR) (Canada) (MP-102638)

Submission date: 24/06/2010
Registration date: 10/08/2010
Last edited: 10/08/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Neonatal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Deborah O'Connor
Scientific

The Hospital for Sick Children
686 Bay Street
Room 10-9706
Toronto
M5G 0A4
Canada

Phone	+1 (0)416 813 7844
Email	deborah_l.oconnor@sickkids.ca

Study information

Primary study design	Interventional
Study design	Pragmatic multicentre double-blind randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Donor human milk versus preterm formula as a substitute for mothers' own milk for feeding very low birth weight infants
Study acronym	DoMINO
Study objectives	Our primary research hypothesis is that very low birth weight (VLBW) infants fed donor milk as a supplement to mothers' own milk for 90 days or until hospital discharge, whichever comes first, will have an improved cognitive composite score at 18 - 24 months corrected age (CA) compared to infants fed preterm formula as a supplement. Our secondary hypotheses are that the use of donor milk compared to formula, as a supplement to mothers' own milk, will: 1. Reduce a composite of death, necrotising enterocolitis (NEC), late onset sepsis, chronic lung disease and severe retinopathy of prematurity 2. Support growth 3. To improve language and motor development Exploratory research questions are will the use of donor milk, as a supplement to mothers' own milk: 1. Influence feeding tolerance and nutrient intake? 2. Have an acceptable cost effectiveness from comprehensive societal perspective?
Ethics approval(s)	Research Ethics Board for The Hospital for Sick Children, ref: 1000017662
Health condition(s) or problem(s) studied	Neurodevelopmental outcomes
Intervention	Treatment Group: Infants randomised to the intervention group will receive donor milk when mothers' own milk is unavailable. Infants will continue to receive donor milk after transfer to a participating Level II NICU for 90 days after randomisation or discharge home, whichever occurs first. Control Group: Infants randomised to the control group will receive formula designed for preterm infants when mothers' own milk is unavailable. Infants will continue to receive formula after transfer to a participating Level II NICU for 90 days after randomization or discharge home, whichever occurs first.
Intervention type	Other
Primary outcome measure(s)	Cognitive composite score on the Bayley Scales of Infant and Toddler Development-III (BSID-III) at 18 - 24 months corrected age.
Key secondary outcome measure(s)	1. Morbidity/mortality 2. Composite of death, NEC, late onset sepsis, chronic lung disease or severe retinopathy of prematurity (ROP) 3. Growth (Secondary): 3.1. Weight (g/kg/d), length (mm/wk) and head circumference (mm/wk) gain 3.2. Weight-for-age, length-for-age and head circumference-for-age z-scores 4. Development (Secondary): 4.1. Language and motor composite scores on the BSID-III at 18-24 months corrected age 5. Feeding Tolerance and Nutrient Intake (Exploratory) 5.1. Days to full enteral feeding (150 ml/kg/d) 5.2. Days feedings withheld 5.7. Estimated energy and select nutrient intakes (protein, fat, calcium, phosphorus, iron, zinc) 6. Growth and Breastfeeding (Exploratory) 6.1. Weight-for-age, length-for-age and head circumference-for-age z-scores to 18-24 months corrected age 6.2. Duration (days) of human milk feeding (mothers own milk) 6.3. Exclusivity of human milk feeding (mothers own milk) at each infants 4, 6 and 12 months corrected age 7. Cost effectiveness (medical and non-medical) from a societal perspective (Exploratory) Added 20/09/2017: 8. Gut microbiome characterization (Exploratory
Completion date	17/07/2015

Eligibility

Participant type(s)	Patient
Age group	Neonate
Sex	All
Target sample size at registration	352
Total final enrolment	363
Key inclusion criteria	1. Day 1 to 4 of life 2. Less than 1500 g birth weight 3. Enteral feeding is expected to be initiated in the first 7 days of life
Key exclusion criteria	1. Infants with serious congenital or chromosomal anomalies that may contribute to serious developmental outcome 2. Asphyxia (hypoxia or ischaemia) as defined by all of: 2.1. Severe metabolic or mixed acidaemia (pH less than 7.00 or base deficit less than -16) on an umbilical cord arterial blood sample or neonatal blood gas within first hour of life 2.2. Apgar score of 0 - 3 for greater than 5 minutes 2.3. Multi-organ system dysfunction within 72 hours of birth 3. Enrolment in any other clinical study affecting nutritional management during the feeding intervention 4. Reasonable potential that the infant will be transferred to a Neonatal Intensive Care Unit (NICU) or Level II NICU where the study protocol will not be continued
Date of first enrolment	14/09/2010
Date of final enrolment	19/12/2012

Locations

Countries of recruitment

Canada

Study participating centre

The Hospital for Sick Children

Toronto
M5G 1X8
Canada

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	08/11/2016		Yes	No
Results article	results	01/03/2018		Yes	No
Results article	results	01/12/2019	20/09/2019	Yes	No
Results article	results	01/02/2020	11/10/2019	Yes	No
Results article	follow up results	01/02/2020	10/08/2020	Yes	No
Protocol article	protocol	13/05/2014		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

10/08/2020: The following changes were made to the trial record:
1. Publication reference added.
2. The ClinicalTrials.gov number was added.
11/10/2019: Publication reference added.
20/09/2019: Publication reference and total final enrolment added.
19/03/2018: Publication reference added.
20/09/2017: Secondary outcome measures have been updated.
10/11/2016: Publication reference added.
31/05/2016: The overall trial end date has been updated from 15/09/2014 to 17/07/2015 and the recruitment end date has been updated from 15/09/2014 to 19/12/2012.
23/05/2016: The third secondary hypothesis (to improve visual, language and motor development) has been edited. Additionally, the following has been removed from the secondary outcome measures:
"5. Visual Evoked Potential (Secondary)
5.1. Visual acuity at 4 and 6 months corrected age
5.2. Contrast sensitivity at 4 and 6 months corrected age"