P3.B023: Early versus late fortification of human milk in preterm infants: a meta-analysis of randomized controlled trials

Background: Fortifying human milk may improve the growth of preterm infants. However, the optimal timing for its initiation remains uncertain. This systematic review and meta-analysis aim to compare the effects of early versus late initiation fortifiers in preterm infants.

Methods: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) comparing early versus late fortification of human milk in preterm infants. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (95%CI) were pooled using a random-effects model. Statistical analyses were performed using R version 4.3.2.

Results: Four RCTs comprising 419 preterm infants were included, of whom 49.6% were male, with a mean gestational age of 29.0 weeks. Late fortification of human milk significantly decreased the length of hospital stay as compared with early fortification (MD 4.41 days; 95% CI 0.17 to 8.66; p=0.042; Figure A). There were no significant differences in terms of sepsis (RR 0.83; 95% CI 0.52 to 1.35; p=0.460; Figure B), necrotizing enterocolitis (RR 1.59; 95% CI 0.55 to 4.57; p=0.388; Figure C), feeding intolerance (RR 1.24; 95% CI 0.85 to 1.81; p=0.268; Figure D), or weight growth velocity (MD 1.20g/Kg/day; 95% CI -0.09 to 2.49; p=0.068; Figure E).

Conclusion: This meta-analysis of RCTs suggests that late initiation of fortifiers in human milk may reduce length of stay in preterm infants, without significantly affecting complication rates, feeding intolerance or growth.