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Background <p>Fortification of breast milk with milk-derived fortifiers is essential for the growth and developmental outcomes of preterm infants, yet the ideal fortifier remains uncertain. This network meta-analysis assessed the effects of bovine milk-derived fortifier (BMF), human milk-derived fortifier (HMF), and donkey milk-derived fortifier (DMF) on morbidity and mortality rates of preterm infants within neonatal intensive care units (NICUs).</p> Methods <p>We conducted a comprehensive search of multiple databases, including MEDLINE, CINAHL, PubMed, CNKI, and the Cochrane Central Register of Controlled Trials. The risk of bias for each study was evaluated using the Cochrane Risk of Bias 2 (RoB 2) tool.</p> Results <p>Ten studies involving 545 preterm infants were identified for qualitative descriptive analysis. network meta-analysis was conducted, incorporating data from five studies and three different types of milk-based fortifiers. The network meta-analysis suggested that HMF may be associated with a lower incidence of necrotizing enterocolitis. Compared with HMF, BMF was associated with an increased risk of necrotizing enterocolitis (RR = 2.33, 95% CI [1.22–4.44]). Cumulative ranking probabilities indicated that HMF appeared to be the most favourable fortifier for reducing both necrotizing enterocolitis incidence and mortality. DMF might represent a potential option for reducing the risk of intraventricular haemorrhage and neonatal sepsis.</p> Conclusion <p>HMF may be associated with a reduced incidence of necrotizing enterocolitis, whereas DMF may offer potential anti-inflammatory benefits, particularly for high-risk populations susceptible to intraventricular haemorrhage. This study provides direct and comparative evidence of the associations between different animal-derived fortifiers and morbidity and mortality in preterm infants. It provides a preliminary evaluation of DMF, for which limited evidence previously existed, and offers insight into the potential mechanisms that connect milk composition to clinical outcomes. However, these findings are primarily based on a limited number of studies with small sample sizes. Further randomized controlled trials are necessary to validate these observations.</p>

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Impact of three mammalian milk-derived fortifiers on morbidity and mortality in preterm infants: a systematic review and network meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月25日

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  • Yueqing Feng,
  • Yan Gao,
  • Yue Gu,
  • Yujie Liu,
  • Yunyun Xu,
  • Shenmei Li

摘要

Background

Fortification of breast milk with milk-derived fortifiers is essential for the growth and developmental outcomes of preterm infants, yet the ideal fortifier remains uncertain. This network meta-analysis assessed the effects of bovine milk-derived fortifier (BMF), human milk-derived fortifier (HMF), and donkey milk-derived fortifier (DMF) on morbidity and mortality rates of preterm infants within neonatal intensive care units (NICUs).

Methods

We conducted a comprehensive search of multiple databases, including MEDLINE, CINAHL, PubMed, CNKI, and the Cochrane Central Register of Controlled Trials. The risk of bias for each study was evaluated using the Cochrane Risk of Bias 2 (RoB 2) tool.

Results

Ten studies involving 545 preterm infants were identified for qualitative descriptive analysis. network meta-analysis was conducted, incorporating data from five studies and three different types of milk-based fortifiers. The network meta-analysis suggested that HMF may be associated with a lower incidence of necrotizing enterocolitis. Compared with HMF, BMF was associated with an increased risk of necrotizing enterocolitis (RR = 2.33, 95% CI [1.22–4.44]). Cumulative ranking probabilities indicated that HMF appeared to be the most favourable fortifier for reducing both necrotizing enterocolitis incidence and mortality. DMF might represent a potential option for reducing the risk of intraventricular haemorrhage and neonatal sepsis.

Conclusion

HMF may be associated with a reduced incidence of necrotizing enterocolitis, whereas DMF may offer potential anti-inflammatory benefits, particularly for high-risk populations susceptible to intraventricular haemorrhage. This study provides direct and comparative evidence of the associations between different animal-derived fortifiers and morbidity and mortality in preterm infants. It provides a preliminary evaluation of DMF, for which limited evidence previously existed, and offers insight into the potential mechanisms that connect milk composition to clinical outcomes. However, these findings are primarily based on a limited number of studies with small sample sizes. Further randomized controlled trials are necessary to validate these observations.