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

NCT ID: NCT06870318

Last Updated: 2025-03-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 355 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-10-01
• Study Completion Date: 2022-09-01

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

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: RETROSPECTIVE

Study Groups

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

No intervention; Observational study

Intervention Type: 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

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

No intervention; Observational study

Intervention Type: 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.

Interventions

No intervention; Observational study

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 1 Hour
• Maximum Eligible Age: 21 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Umeå University

OTHER

Sponsor Role: collaborator

Region Östergötland

OTHER

Sponsor Role: collaborator

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Deborah O'Connor

Senior Associate Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Deborah L O'Connor, PhD, RN

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Magnus Domellöf, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Umeå University, Umeå (UMU)

Locations

The Hospital for Sick Children

Toronto, Ontario, Canada

Umeå University

Umeå, , Sweden

Countries

Canada; Sweden

References

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.

Reference Type: BACKGROUND

PMID: 34815288 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32367115 (View on PubMed)

Other Identifiers

4784

Identifier Type: -

Identifier Source: org_study_id