Clinical trial NCT06870318: Enrichment of Human Milk With Human and Bovine Milk-based Fortifiers for Very Preterm Infants: a Meta-analysis
Official title: Nutrient Enrichment of Human Milk With Human and Bovine Milk-based Fortifiers for Very Preterm Infants: an Individual Participant Data Meta-analysis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Human Milk Fortification
Very Low Birth Weight Baby
Human Milk Nutrition
Human Milk Feeding
Necrotizing Enterocolitis (NEC)
Late Onset Neonatal Sepsis
Growth
Feeding Intolerance in Preterm
Infant Mortality
Keywords: Bovine based vs human milk based fortifiers
RCTs meta-analysis
Human Milk Fortifiers (HMF)
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Umeå University
name: Region Östergötland
First posted: 2025-03-11
Enrollment: 355
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants of the OptiMoM and N-Forte trial are VLBW infants fed exclusively Human Milk.

Brief summary: Research has shown that provision of mother's milk is the optimal way to feed very low birthweight (VLBW) infants. Many infants will require a supplement to mother's milk, pasteurized donor human milk (PDHM) compared to preterm formula is the most appropriate supplement as it has been shown to reduce the risk of necrotizing enterocolitis (NEC).

Most available evidence suggests neither mother's milk nor PDHM will meet the elevated nutritional requirements of VLBW infants without multi-nutrient fortification. Globally, the current standard of care is to use bovine protein-based nutrient fortifiers to meet these elevated nutrient requirements. Given the known benefits of mother's milk, the reduction in the risk of NEC with use of PDHM as a supplement, and the availability of human milk-based multi-nutrient fortifiers (HMBF), there has been considerable interest in the efficacy of HMBF over the less costly bovine milk-based fortifiers (BMBF).

This study is an analysis of individual participant data merged from randomized control trials that examined the efficacy of HMBF compared to BMBF during hospitalization, on the risk of death and severe morbidity or major feeding interruption. Participants of the trials included in the analyses were fed exclusively with human milk or a supplement of pasteurized donor human milk (PDHM).

Only two RCTs met this criteria -OptiMoM and the N-forte trial. In both studies the intervention aligned to commence upon randomization into the HMBF or BMBF groups. The difference between the OptiMoM and N-forte feeding protocols was that the later allowed for individualized fortification based on milk analysis whereas OptiMoM used standard fortification, predominant in Canada and globally.

For OptiMoM, the feeding intervention continued until infants were 84 days of age, discharge, or when the infant consumed ≥2 complete oral feeds daily. For N-forte trial, the feeding intervention ended when babies reached 34 weeks (zero days). Both studies followed participants and continued data collection if transferred to a level II NICU for convalescence (OptiMoM) or home care service followed closely by NICU nurses (N-forte) until discharge.


Eligibility criteria: Inclusion Criteria:

• Infant is a participant of the OptiMoM or the N-Forte trial.

Primary outcomes:
measure: Number of participants with composite of NEC (NEC II-III), culture-proven late-onset sepsis and mortality.
timeFrame: From study day 1 through hospitalization, approximately 60 days.
measure: Percentage of infants with an interruption in enteral feeding.
timeFrame: Through feeding intervention, approximately 50 days.
Secondary outcomes:
measure: Days from birth to full enteral feeding.
timeFrame: Approximately 10 days.
measure: Number of participants with NEC II-III.
timeFrame: From study day 1 through hospitalization, approximately 60 days.
measure: Number of participants with late onset-sepsis.
timeFrame: From study day 1 through hospitalization, approximately 60 days.
measure: Total deaths prior to discharge.
timeFrame: From study day 1 through hospitalization, approximately 60 days.
measure: Number of participants with bronchopulmonary dysplasia.
timeFrame: Assessed at 36 weeks 0 days post-conceptional age.
measure: Number of participants with severe retinopathy of prematurity (ROP).
timeFrame: From study day 1 through hospitalization, approximately 60 days.
Other outcomes:
measure: Cause of death prior to discharge.
timeFrame: From study day 1 through hospitalization, approximately 60 days.
measure: Number of participants with surgical NEC.
timeFrame: From study day 1 through hospitalization, approximately 60 days.
measure: Mortality and morbidity index.
timeFrame: From study day 1 through hospitalization, approximately 60 days.
measure: Number of withdrawals.
timeFrame: From study day 1 through hospitalization, approximately 60 days.
measure: Days on parenteral nutrition.
timeFrame: Through feeding intervention, approximately 50 days.
measure: Percentage of enteral feeds fed as mother's versus PDHM.
timeFrame: Through feeding intervention, approximately 50 days.
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Umeå
country: Sweden
facility: Umeå University
Study officials:
affiliation: The Hospital for Sick Children
name: Deborah L O'Connor, PhD, RN
role: PRINCIPAL_INVESTIGATOR
affiliation: Umeå University, Umeå (UMU)
name: Magnus Domellöf, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jensen GB, Ahlsson F, Domellof M, Elfvin A, Naver L, Abrahamsson T. Nordic study on human milk fortification in extremely preterm infants: a randomised controlled trial-the N-forte trial. BMJ Open. 2021 Nov 23;11(11):e053400. doi: 10.1136/bmjopen-2021-053400.
citation: Corrigendum for O'Connor et al. 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;108:108-16. Am J Clin Nutr. 2020 May 1;111(5):1112. doi: 10.1093/ajcn/nqaa042. No abstract available.