Human Milk-Derived Versus Bovine Protein-Based Fortifiers for Preterm Infants Fed Human Milk: A Systematic Review and Meta-Analysis
6 affiliations
- 1Liggins Institute, University of Auckland, Auckland 1023, New Zealand
- 2Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE1 4LP, UK
- 3Department of Pediatrics-Neonatology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, 1005 AZ Amsterdam, The Netherlands
- 4Amsterdam Reproduction and Development Research Institute, 1005 AZ Amsterdam, The Netherlands
- 5Covidence, Future Evidence Foundation, Melbourne 3000, Australia
- 6Starship Child Health, Auckland City Hospital, Auckland 1023, New Zealand
Abstract
Background: Human milk-derived fortifiers (HumBMF) are an alternative to bovine protein-based fortifiers (BovBMF) for preterm infants, but their comparative effectiveness and safety remain uncertain. We evaluated the effects of HumBMF versus BovBMF in preterm or very low birth weight infants. Methods: Randomised controlled trials (RCTs) comparing use of HumBMF versus BovBMF to fortify human milk were identified through four databases and three trial registries (to 11 May 2026). At least two reviewers independently screened studies, extracted data, and assessed risk of bias. Fixed-effect meta-analyses and GRADE assessments were performed. Prespecified analyses separated trials comparing fortifier type alone, in which any mother’s own milk (MOM) shortfall was supplemented with donor human milk (DHM) in both arms; and dual-intervention trials, in which MOM shortfall was also randomised to DHM in the HumBMF arm or preterm formula in the BovBMF arm. Results: Nine RCTs were included. In trials comparing fortifier type alone, there was no evidence that HumBMF reduced mortality (RR 0.60 (95% CI 0.29–1.23), low-certainty) or necrotising enterocolitis (NEC; RR 0.83 (0.39–1.78), very low-certainty). In dual-intervention trials, where MOM shortfall was supplemented with DHM rather than formula, NEC was lower (RR 0.45 (0.20–0.99), moderate-certainty). Conclusions: Current evidence does not demonstrate clinical advantages of HumBMF over BovBMF when added to the same human milk diet. Reductions in NEC occurred only where DHM also replaced preterm formula and cannot be attributed to fortifier type alone. Future research should distinguish the independent effects of fortifier composition from those of an exclusive human milk feeding strategy.
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BibTeX
@article{lin2026human,
title = {{Human Milk-Derived Versus Bovine Protein-Based Fortifiers for Preterm Infants Fed Human Milk: A Systematic Review and Meta-Analysis}},
author = {Luling Lin and Nicholas D. Embleton and Chris H. P. Van Den Akker and Julie Brown and Lilia Delgado Paramo and Barbara E. Cormack},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18193288},
url = {https://europepmc.org/article/PMC/PMC13666894},
note = {CC BY},
}
RIS
TY - JOUR
TI - Human Milk-Derived Versus Bovine Protein-Based Fortifiers for Preterm Infants Fed Human Milk: A Systematic Review and Meta-Analysis
AU - Luling Lin
AU - Nicholas D. Embleton
AU - Chris H. P. Van Den Akker
AU - Julie Brown
AU - Lilia Delgado Paramo
AU - Barbara E. Cormack
PY - 2026
DA - 2026/10/01
JO - Nutrients
DO - 10.3390/nu18193288
UR - https://europepmc.org/article/PMC/PMC13666894
AB - Background: Human milk-derived fortifiers (HumBMF) are an alternative to bovine protein-based fortifiers (BovBMF) for preterm infants, but their comparative effectiveness and safety remain uncertain. We evaluated the effects of HumBMF versus BovBMF in preterm or very low birth weight infants. Methods: Randomised controlled trials (RCTs) comparing use of HumBMF versus BovBMF to fortify human milk were identified through four databases and three trial registries (to 11 May 2026). At least two reviewers independently screened studies, extracted data, and assessed risk of bias. Fixed-effect meta-analyses and GRADE assessments were performed. Prespecified analyses separated trials comparing fortifier type alone, in which any mother’s own milk (MOM) shortfall was supplemented with donor human milk (DHM) in both arms; and dual-intervention trials, in which MOM shortfall was also randomised to DHM in the HumBMF arm or preterm formula in the BovBMF arm. Results: Nine RCTs were included. In trials comparing fortifier type alone, there was no evidence that HumBMF reduced mortality (RR 0.60 (95% CI 0.29–1.23), low-certainty) or necrotising enterocolitis (NEC; RR 0.83 (0.39–1.78), very low-certainty). In dual-intervention trials, where MOM shortfall was supplemented with DHM rather than formula, NEC was lower (RR 0.45 (0.20–0.99), moderate-certainty). Conclusions: Current evidence does not demonstrate clinical advantages of HumBMF over BovBMF when added to the same human milk diet. Reductions in NEC occurred only where DHM also replaced preterm formula and cannot be attributed to fortifier type alone. Future research should distinguish the independent effects of fortifier composition from those of an exclusive human milk feeding strategy.
SN - 2072-6643
ER -