Early versus delayed introduction of human milk fortification in enterally fed preterm infants: A systematic review and meta‐analysis

Aim To assess effects of early versus delayed introduction of human milk fortification in preterm infants. Methods We searched Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PubMed and CINAHL for randomised controlled trials evaluating start time for human milk fortification in preterm infants (March 2020). Two authors assessed trial eligibility and risk of bias, extracted data and assessed evidence certainty. Results We identified 1307 publications and included three trials (378 infants). Meta‐analysis comparing fortification commencing at an enteral feed volume of ≤40 mL/kg/day versus ≥75 mL/kg/day, showed little to no difference in rates of necrotising enterocolitis (3 trials), sepsis (3 trials), feeding intolerance (2 trials) (low‐quality evidence) and infant growth (1 trial, very low‐quality evidence). Conclusions Whether early introduction of fortification, at an enteral feed volume of ≤40 mL versus delayed at ≥75 mL/kg/day improves growth or influences adverse feeding outcomes is very uncertain.