Clinical trial NCT02137473: Bovine vs. Human Milk-Based Fortifier Study
Official title: Optimizing Mothers' Milk for Preterm Infants (OptiMoM) Program of Research: Study 2-Bovine vs. Human Milk-Based Fortifier Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Very Low Birth Weight Infant (<1250g)
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2014-05-13
Enrollment: 127
Sex: ALL
Maximum age (years): 2
Standard ages: CHILD
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Most very low birth weight infants accumulate a nutrient deficit in hospital due to minimal nutrient reserves and elevated nutritional requirements which may contribute to poor outcome. Adding nutrients to human milk improves their nutritional status and growth, but it is unclear if adding bovine protein-based fortifiers as is the current standard of care has some unintended negative consequences to neonates. Infants will be randomized to have their feeds (mother's own milk or pasteurized donor breastmilk) nutrient enriched with a human milk-based fortifier or a bovine protein-based fortifier and will be followed in hospital to assess feeding tolerance, growth, gut inflammation, mother's milk and infant gut microbiome, and neonatal morbidity and mortality.


Eligibility criteria: Inclusion Criteria:

* \<1250g birth weight
* Parent(s) or guardian(s) agree to use donor breastmilk if own mother's milk supply is insufficient

Exclusion Criteria:

* Infant receives formula or a nutrient fortifier prior to randomization
* \>day 14 at the time of enrollment and enteral feeds have not commenced
* Infants with major congenital or chromosomal anomalies that could impact growth
* Enrollment in another research study affecting nutritional management during the feeding intervention
* Reasonable potential that the infant will be transferred to a neonatal intensive care unit where the study protocol will not be continued

Primary outcomes:
measure: Feeding tolerance
timeFrame: 84 days of age, hospital discharge or when able to consume two oral feeds a day without supplementation (e.g. tube feeding), whichever comes first
Secondary outcomes:
measure: Growth
timeFrame: 84 days of age, hospital discharge or when able to consume two oral feeds a day without supplementation (e.g. tube feeding), whichever comes first
Other outcomes:
measure: Other measures of feeding tolerance
timeFrame: 84 days of age, hospital discharge or when able to consume two oral feeds a day without supplementation (e.g. tube feeding), whichever comes first
measure: Gut inflammation
timeFrame: 84 days of age, hospital discharge or when able to consume two oral feeds a day without supplementation (e.g. tube feeding), whichever comes first
measure: Morbidity/mortality composite
timeFrame: 84 days of age, hospital discharge or when able to consume two oral feeds a day without supplementation (e.g. tube feeding), whichever comes first
measure: Bayley Scales of Infant and Toddler Development (BSID)-III
timeFrame: 18-24 months corrected age
measure: Gut microbiota
timeFrame: 56 days of age or hospital discharge
Locations:
city: Halifax
country: Canada
facility: Izaak Walton Killam Health Centre
state: Nova Scotia
city: Brampton
country: Canada
facility: William Osler Health System-Brampton
state: Ontario
city: Etobicoke
country: Canada
facility: William Osler Health System-Etobicoke
state: Ontario
city: Markham
country: Canada
facility: Markham Stouffville Hospital
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health
state: Ontario
city: Richmond Hill
country: Canada
facility: Mackenzie Health
state: Ontario
city: Toronto
country: Canada
facility: Rouge Valley Health System
state: Ontario
city: Toronto
country: Canada
facility: The Scarborough Hospital-General
state: Ontario
city: Toronto
country: Canada
facility: The Scarborough Hospital-Birchmount
state: Ontario
city: Toronto
country: Canada
facility: North York General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Humber River Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto East General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Toronto
country: Canada
facility: St Joseph's Health Centre
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children, University of Toronto
name: Deborah L O'Connor, PhD RD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mount Sinai Hospital, University of Toronto
name: Sharon L Unger, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Asbury MR, Shama S, Sa JY, Bando N, Butcher J, Comelli EM, Copeland JK, Forte V, Kiss A, Sherman PM, Stintzi A, Taibi A, Tomlinson C, Unger S, Wang PW, O'Connor DL; OptiMoM Feeding Group. Human milk nutrient fortifiers alter the developing gastrointestinal microbiota of very-low-birth-weight infants. Cell Host Microbe. 2022 Sep 14;30(9):1328-1339.e5. doi: 10.1016/j.chom.2022.07.011. Epub 2022 Aug 19.
citation: Hopperton KE, Pitino MA, Walton K, Kiss A, Unger SL, O'Connor DL, Bazinet RP. Docosahexaenoic acid and arachidonic acid levels are correlated in human milk: Implications for new European infant formula regulations. Lipids. 2022 May;57(3):197-202. doi: 10.1002/lipd.12338. Epub 2022 Feb 15.
citation: Hopperton KE, Pitino MA, Chouinard-Watkins R, Shama S, Sammut N, Bando N, Williams BA, Walton K, Kiss A, Unger SL, Bazinet RP, O'Connor DL. Determinants of fatty acid content and composition of human milk fed to infants born weighing <1250 g. Am J Clin Nutr. 2021 Oct 4;114(4):1523-1534. doi: 10.1093/ajcn/nqab222.
citation: Hopperton KE, O'Connor DL, Bando N, Conway AM, Ng DVY, Kiss A, Jackson J, Ly L; OptiMoM Feeding Group; Unger SL. Nutrient Enrichment of Human Milk with Human and Bovine Milk-Based Fortifiers for Infants Born <1250 g: 18-Month Neurodevelopment Follow-Up of a Randomized Clinical Trial. Curr Dev Nutr. 2019 Nov 12;3(12):nzz129. doi: 10.1093/cdn/nzz129. eCollection 2019 Dec.
citation: O'Connor DL, Kiss A, Tomlinson C, Bando N, Bayliss A, Campbell DM, Daneman A, Francis J, Kotsopoulos K, Shah PS, Vaz S, Williams B, Unger S; OptiMoM Feeding Group. Nutrient enrichment of human milk with human and bovine milk-based fortifiers for infants born weighing <1250 g: a randomized clinical trial. Am J Clin Nutr. 2018 Jul 1;108(1):108-116. doi: 10.1093/ajcn/nqy067.