Objective To conduct a systematic review and meta-analysis of the efficacy and safety of fortification of human milk with human milk-based fortifier versus cow’s milk-based fortifier for use in preterm and/or very low birthweight infants.
Design Randomised or quasi-randomised controlled trials comparing the effect of human milk fortification with human milk-based milk fortifier versus cow’s milk-based fortifier in infants born <34 weeks’ gestation and/or with birth weight <1500 g were identified by searching databases, clinical trial registries and reference lists until 5 November 2019. Two authors independently extracted data and assessed evidence quality. Meta-analyses were conducted using fixed or random effects models, as appropriate.
Main outcome measures Necrotising enterocolitis (Bell’s stage II or higher) and late-onset sepsis.
Results Of 863 unique records identified, 16 full-text trials were screened and 2 trials involving 334 infants were included. Primary outcome data were available for 332 infants. Use of human milk-based fortifier compared with cow’s milk-based fortifier reduced the risk of necrotising enterocolitis (risk ratio 0.47, 95% CI 0.22 to 0.98). There was no clear evidence of an effect on late-onset sepsis or any other outcomes. The quality of evidence was low to very low due to imprecision and lack of blinding in one study.
Conclusions Findings suggest that there is a reduction in the incidence of necrotising enterocolitis with human milk-based fortifiers compared with cow’s milk-based fortifiers. The overall quality of evidence is low. Further appropriately powered trials are required before this intervention can be routinely recommended for preterm infants.
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Contributors EG and AKK had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: EG, AKK, CTC, JG, CH. Acquisition, analysis or interpretation of the data: EG, AKK, CTC, JG, CH, AR. Drafting of the manuscript: EG, CTC, JG. Critical review of the manuscript for important intellectual content: EG, AKK, CTC, JG, CH, AR. Statistical analysis: EG, JG. Obtained funding: AKK, CTC. Administrative, technical or material support: AR, CTC. Study supervision: AKK, JG.
Funding CTC and AKK are in receipt of National Health and Medical Research Council (NHMRC) Fellowships (APP1132596 and APP1161379, respectively). The views expressed in this article are solely the responsibility of the authors and do not reflect the views of the NHMRC.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement As this is a systematic review and meta-analysis, all relevant data are included in the article or uploaded as supplementary information.