Enrichment of Human Milk With Human and Bovine Milk-based Fortifiers for Very Preterm Infants: a Meta-analysis

NCT06870318 | Completed

• 1 other identifier: 4784
• Study Type: observational
• Target: 355
• Locations: 2 countries
• Sites: 2

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.

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)

Outcome Measures

Primary Outcomes (2)

• Number of participants with composite of NEC (NEC II-III), culture-proven late-onset sepsis and mortality.

  The first primary outcome is a binary (yes/no) composite of NEC (NEC II-III), culture-proven late-onset sepsis and mortality.

  From study day 1 through hospitalization, approximately 60 days.

• Percentage of infants with an interruption in enteral feeding.

  The second primary outcome is the percentage of infants with an interruption in enteral feeding after commencement of the intervention (e.g. Study Day 1), unrelated to a clinical procedure, that lasted for ≥12 h or a \>50% reduction in volume over the same time-frame.

  Through feeding intervention, approximately 50 days.

Secondary Outcomes (6)

• Days from birth to full enteral feeding.

  Approximately 10 days.

• Number of participants with NEC II-III.

  From study day 1 through hospitalization, approximately 60 days.

• Number of participants with late onset-sepsis.

  From study day 1 through hospitalization, approximately 60 days.

• Total deaths prior to discharge.

  From study day 1 through hospitalization, approximately 60 days.

• Number of participants with bronchopulmonary dysplasia.

  Assessed at 36 weeks 0 days post-conceptional age.

Other Outcomes (6)

• Cause of death prior to discharge.

  From study day 1 through hospitalization, approximately 60 days.

• Number of participants with surgical NEC.

  From study day 1 through hospitalization, approximately 60 days.

• Mortality and morbidity index.

  From study day 1 through hospitalization, approximately 60 days.

Study Arms (2)

Human milk-based multi-nutrient fortifiers (HMBF) group

Infants born VLBW fed exclusively with Human Milk (parent milk or pasteurized donor milk) fortified with HMBF

Other: No intervention; Observational study

Bovine milk-based fortifiers (BMBF) group

Infants born VLBW fed exclusively with Human Milk (parent milk or pasteurized donor milk) fortified with BMBF

Other: No intervention; Observational study

Interventions

No intervention; Observational study OTHER

OptiMoM-NForte is meta-analysis study (observational secondary use of data), the investigators will analyze data from the OptiMoM and NForte trials. No interventions form part of this study.

Bovine milk-based fortifiers (BMBF) group; Human milk-based multi-nutrient fortifiers (HMBF) group

Eligibility Criteria

• Age: 1 Hour - 21 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Participants of the OptiMoM and N-Forte trial are VLBW infants fed exclusively Human Milk.

You may qualify if:

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

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Umeå University: collaborator
• Region Östergötland: collaborator

Study Sites (2)

The Hospital for Sick Children

Toronto, Ontario, M5G 0A4, Canada

Location

Umeå University

Umeå, SE-901 87, Sweden

Location

Related Publications (2)

• 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.

  PMID: 34815288 BACKGROUND

• 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.

  PMID: 32367115 BACKGROUND

MeSH Terms

Conditions

Enterocolitis, Necrotizing; Neonatal Sepsis; Infant Death

Interventions

Observation

Condition Hierarchy (Ancestors)

Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Sepsis; Infections; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Death

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Deborah L O'Connor, PhD, RN

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Magnus Domellöf, MD, PhD

  Umeå University, Umeå (UMU)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Associate Scientist

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: March 11, 2025
• Study Start: October 1, 2014
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: February 2025 to February 2027
• Access Criteria: The Hospital for Sick Children (Lead Dr. Deborah L. O'Connor PhD, RD): Data analysis. Umeå University - (Lead Dr. Magnus Domellöf MD, PhD): Data analysis.

Locations

CA (1); SE (1)