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.
Conclusion
Our data associates bovine milk-derived fortifiers with a possibly increased risk of death, which makes a reversal possibly necessary. However, the introduction of bovine milk fortifiers cannot yet be judged due to the lack of sufficiently powered clinical trials and the lack of relevant information about the long-term outcomes in terms of neurodevelopment. Although BPD itself is a disease for life and is associated with poorer neurodevelopmental outcomes, we need neurodevelopmental follow-up data from all survivors to definitely address the question of if the use of an exclusive human milk diet from MOM and/or pooled DM is warranted due to the unique nutritional and immunological benefits from human breast milk which can reduce the relevant outcomes of an extremely low gestational period. The results should not be refuted for formal reasons but should be taken as the need to further define the effects of a human milk diet (MOM and/or pooled DM) supplemented with human milk fortifiers.