Human breast milk fortification with human milk fortifier vs preterm infant formula: A systematic review and meta-analysis

Abstract

Background

The limited availability and high cost of human milk fortifier (HMF) in developing countries represent significant challenges. Preterm formula (PTF) fortification of breast milk is a potential alternative, but its safety and impact on growth are still uncertain. This study compares the safety and effect of breast milk fortification with PTF versus HMF on growth velocity in very low birth weight preterm infants.

Methods

A thorough literature search was conducted in the PubMed, Scopus, Google Scholar, ClinicalTrials.gov, and Europe PMC databases up to March 24, 2024. Relevant randomized controlled trials (RCTs) studying fortifying breast milk with PTF or HMF were identified and their quality assessed using the Cochrane Risk of Bias 2 tool. Statistical analysis was performed in Review Manager Web, and certainty of evidence was assessed with GRADE.

Results

Six RCTs were included, of which one exhibited low bias risk, three had moderate concerns, and two were classed as high risk. The six RCTs, involving 434 preterm infants, revealed no significant differences in the gain of weight (SMD 0, 95% CI −0.19 to 0.19), length (MD −0.01 cm/wk, 95% CI −0.06 to 0.05), or head circumference (MD −0.01 cm/wk, 95% CI −0.06 to 0.04) between PTF and HMF. There were comparable risks of morbidities.

Conclusion

Very low certainty evidence suggests that breast milk fortification with PTF may be a safe alternative to HMF, with similar safety profiles and effects on growth.