Comparative effectiveness of liquid human milk fortifiers: A systematic review and meta-analysis

Objective: To determine the effectiveness of liquid human milk fortifiers (HMFs) derived from exclusive HM or hydrolyzed protein on growth, necrotizing enterocolitis (NEC), or late-onset sepsis in North American very low-birth-weight (VLBW) infants compared with powder HMFs (control). Methods: Prospective trials published between 2009 and 2020 were systematically reviewed, and meta-analysis was conducted by using a random-effects model. Results: Five studies were identified for up to 591 participants across 39 centers. Study treatments included whey or casein hydrolysate HMF and exclusive HM HMF. Infants fed whey or casein hydrolysate HMF had growth differences compared with the control. No differences were found across treatments in regard to NEC or sepsis. Conclusion: Very low-quality evidence suggests greater linear growth in VLBW infants fed whey hydrolysate liquid HMF, as well as greater weight gain in those fed casein hydrolysate HMF, compared with the control. Additional prospective, multicenter randomized controlled trials are needed to confirm these estimates because of sparsity of evidence. There is insufficient evidence to support HMF decisions regarding NEC or late-onset sepsis prophylaxis.