Human Milk-Derived Fortifiers Compared with Bovine Milk-Derived Fortifiers in Preterm Infants: A Systematic Review and Meta-Analysis

This systematic review assessed outcomes after using human milk-derived fortifier (HMF) compared with bovine milk-derived fortifier (BMF) in preterm infants. Six randomized controlled trials (RCTs) were included. Meta-analysis using a random-effects model showed the following results: 1) lower risk of necrotizing enterocolitis (NEC; ≥Stage II) (RR: 0.38; 95% CI: 0.15, 0.95; P = 0.04, I2 = 9%; n = 334, 4 RCTs) and surgical NEC (RR: 0.13; 95% CI: 0.02, 0.67; P = 0.02, I2 = 0%; n = 209, 3 RCTs) in the HMF group; 2) no significant difference in mortality (RR: 0.40; 95% CI: 0.14, 1.15; P = 0.09, I2 = 0%; n = 334, 4 RCTs); 3) lower weight gain in the HMF group [mean difference (MD) = -1.08 g · kg-1 · d-1; 95% CI: -1.96, -0.21 g · kg-1 · d-1; P = 0.02, I2 = 0%; n = 241, 4 RCTs]; 4) no differences for length (MD = -0.11 cm/wk; 95% CI: -0.26, 0.04 cm/wk; P = 0.14, I2 = 68%) and head circumference (MD = -0.02 cm/wk; 95% CI: -0.08, 0.05 cm/wk; P = 0.59, I2 = 23%); and 5) no significant difference in late-onset sepsis (RR: 0.96; 95% CI: 0.56, 1.67; P = 0.90, I2 = 63%; n = 334, 4 RCTs). The beneficial effects of HMF for NEC were no longer significant in sensitivity analyses after excluding studies with high risk of bias. Quality of evidence as per Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis was low to very low, and hence the confidence in these results is low. In summary, fortification of milk in preterm infants with HMF compared with BMF decreased the risk of NEC but was associated with lower weight gain. Given the low quality of evidence, adequately powered and well-designed RCTs without the influence of industry are required in this field.