Elsevier

Advances in Nutrition

Volume 11, Issue 5, September 2020, Pages 1325-1333
Advances in Nutrition

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

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ABSTRACT

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.

bovine
human milk fortifier
preterm
necrotizing enterocolitis
breast milk

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The authors reported no funding received for this study.

Author disclosures: The authors report no conflicts of interest.

Supplemental Tables 1 and 2 and Supplemental Figures 1–3 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/advances/.

Abbreviations used: BMF, bovine milk–derived fortifier; CMP, cow milk protein; ELBW, extremely low birth weight; GRADE, Grading of Recommendations, Assessment, Development and Evaluation; HMF, human milk–derived fortifier; LOS, late-onset sepsis; MD, mean difference; NEC, necrotizing enterocolitis; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RCT, randomized controlled trial; ROB, risk of bias.