Association of Fortification with Human Milk versus Bovine Milk-Based Fortifiers on Short-Term Outcomes in Preterm Infants-A Meta-Analysis

Abstract

This meta-analysis assessed short-term outcomes after using human milk-derived fortifiers (HMFs) compared with bovine milk fortifiers (BMFs) in preterm infants fed an exclusive human milk (HM) diet, either mother's own milk (MOM) or donor human milk (DHM). We searched PubMed, Embase, Google Scholar, CENTRAL and CINHAL between January 2015 and August 2023 for studies reporting outcomes in infants with ≤28 weeks gestation and/or birthweight ≤ 1500 g on an exclusive human milk diet fortified with HMF versus BMF. The primary outcomes were death and NEC (stage ≥ 2). Four studies with a total of 681 infants were included. Mortality was significantly lower in infants fed with an HM-HMFs diet (four studies, 681 infants; RR = 0.50, 95% CI = 0.26-0.94; p = 0.03; I² = 0%), NEC was similar between the two groups (four studies, 681 infants; RR = 0.48, 95% CI = 0.20-1.17; p = 0.11; I²= 39%). BPD was higher in the HM-BMFs group (four studies, 663 infants; RR = 0.83, 95% CI = 0.69-1.000; p = 0.05, I² = 0%), although not statistically significant. No differences were found for sepsis (RR = 0.97, 95% CI = 0.66-1.42; p = 0.96; I² = 26%) or combined ROP (four studies, 671 infants; RR = 0.64, 95% CI = 0.53-1.07; p = 0.28; I² = 69%). An HM-HMFs diet could possibly be associated with decreased mortality with no association with NEC, BPD, sepsis, or ROP. This meta-analysis was limited by the small number of studies included. However, the results should not be refuted for this reason as they provide an impetus for subsequent clinical trials to assess the observed associations.

Keywords: bovine milk protein; extremely preterm infants; human milk fortifier; nutrition; supplement.

Figure 1

PRISMA flow diagram.

Figure 2

Forest plots for primary outcomes. (A). Mortality (all studies, ARR 3.2% NNT-31) [14,15,16,18]. (B). Mortality (RCT’s) [14,15,16]. (C). NEC stage ≥ 2 (all studies) [14,15,16,18]. (D). NEC stage ≥ 2 (RCT’s) [14,15,16].

Figure 3

Forest plots for secondary outcomes. (A). BPD [14,15,16,18]. (B). Late-onset sepsis [14,15,16,18]. (C). ROP [14,15,16,18]. (D). Feed intolerance [14,15]. (E). Growth Velocity [16,18].