Role of human milk in extremely low birth weight infants' risk of necrotizing enterocolitis or death

Division of Neonatology, Department of Pediatrics, Center for Epidemiology and Biostatistics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA.
Journal of perinatology: official journal of the California Perinatal Association (Impact Factor: 2.07). 09/2008; 29(1):57-62. DOI: 10.1038/jp.2008.117
Source: PubMed

ABSTRACT To determine the association between human milk (HM) intake and risk of necrotizing enterocolitis (NEC) or death among infants 401 to 1000 g birth weight.
Analysis of 1272 infants in the National Institute of Child Health and Human Development Neonatal Network Glutamine Trial was performed to determine if increasing HM intake was associated with decreased risk of NEC or death. HM intake was defined as the proportion of HM to total intake, to enteral intake and total volume over the first 14 days. Known NEC risk factors were included as covariates in Cox proportional hazard analyses for duration of survival time free of NEC.
Among study infants, 13.6% died or developed NEC after 14 days. The likelihood of NEC or death after 14 days was decreased by a factor of 0.83 (95% confidence interval, CI 0.72, 0.96) for each 10% increase in the proportion of total intake as HM. Each 100 ml kg(-1) increase in HM intake during the first 14 days was associated with decreased risk of NEC or death (hazard ratio, HR 0.87 (95% CI 0.77, 0.97)). There appeared to be a trend towards a decreased risk of NEC or death among infants who received 100% HM as a proportion to total enteral intake (HM plus formula), although this finding was not statistically significant (HR 0.85 (95% CI 0.60, 1.19)).
These data suggest a dose-related association of HM feeding with a reduction of risk of NEC or death after the first 2 weeks of life among extremely low birth weight infants.

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Available from: Ardythe Luxion Morrow, Sep 27, 2015
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    • "Interestingly , the most highly ranked gene for identifying BF versus FF infants was Endothelial PAS domain-containing protein 1 (EPAS- 1; also known as Hypoxia-inducible factor-2a [HIF-2a]). It is well known that human milk protects preterm infants from the development of NEC, one of the most common causes of morbidity and mortality in very low birth weight infants [62] [63]. We postulate that induction of this gene may provide a mechanism whereby the intestines of premature infants fed human milk are better able to tolerate episodes of hypoxia and are thereby less likely to develop NEC. "
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    ABSTRACT: The early postnatal period is a critical window for intestinal and immune maturation. Intestinal development and microbiome diversity and composition differ between breast- (BF) and formula-fed (FF) infants. Mechanistic examination into host–microbe relationships in healthy infants has been hindered by ethical constraints surrounding tissue biopsies. Thus, a statistically rigorous analytical framework to simultaneously examine both host and microbial responses to dietary/environmental factors using exfoliated intestinal epithelial cells was developed. Differential expression of ∼1200 genes, including genes regulating intestinal proliferation, differentiation and barrier function, was observed between BF and FF term infants. Canonical correlation analysis uncovered a relationship between microbiome virulence genes and host immunity and defense genes. Lastly, exfoliated cells from preterm and term infants were compared. Pathways associated with immune cell function and inflammation were up-regulated in preterm, whereas cell growth-related genes were up-regulated in the term infants. Thus, coordinate measurement of the transcriptomes of exfoliated epithelial cells and microbiome allows inquiry into mutualistic host–microbe interactions in the infant, which can be used to prospectively study gut development or, retrospectively, to identify potential triggers of disease in banked samples.
    FEBS Letters 11/2014; 588(22). DOI:10.1016/j.febslet.2014.07.008 · 3.17 Impact Factor
    • "Additional data would suggest that there is a dose-related benefit of human milk intake. In a retrospective analysis of the National Institute of Child Health and Human Development Neonatal Network Glutamine Trial, researchers noted that for each 10% increase in the proportion of human milk consumption, the incidence of NEC was lower by a factor of 0.83.[25] In another study, only 3% of infants who received more than 50% as human milk developed NEC, whereas 10% of infants who received <50% of their total enteral intake as human milk developed NEC.[26] "
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    ABSTRACT: Necrotizing enterocolitis (NEC) remains a very devastating problem within the very low birth weight neonatal population. Several experimental therapies are being tested in animal models and soon may be ready for human trials. Despite this progress, we currently have no way to identify infants who would be optimal targets for therapy. Specifically, we are unable to predict which infants will progress to the more severe Bell's stage of disease that may necessitate surgery. Ideally, an algorithm could be constructed that would encompass multiple neonatal and maternal risk factors as well as potential biologic markers of disease so that these infants could be identified in a more timely fashion. This review summarizes the known risk factors and biomarkers of disease in hopes of stimulating clinical research to identify such an "early warning" NEC algorithm.
    03/2014; 3(1):1-9. DOI:10.4103/2249-4847.128717
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    • "The benefits of human milk compared to the use of commercial infant formulas are largely realized because of its bioactive components, including prebiotics, immune proteins and the microbiome of human milk itself. Breastfeeding is associated with a decreased incidence of gastrointestinal (GI) tract infections [1,2], which is corroborated by several studies that have correlated breastfeeding with a lower incidence of necrotizing enterocolitis in humans and animal models [3-5]. Breastfeeding is also associated with an altered fecal microbiome; two studies showed at two weeks of age over 90% of the total fecal bacteria of a breast-fed (BF) infant is Bifidobacteria, whereas in most formula-fed (FF) infants Bifidobacteria is non-detectable [6,7]. "
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    ABSTRACT: Background Human milk contains a diverse population of bacteria that likely influences colonization of the infant gastrointestinal tract. Recent studies, however, have been limited to characterization of this microbial community by 16S rRNA analysis. In the present study, a metagenomic approach using Illumina sequencing of a pooled milk sample (ten donors) was employed to determine the genera of bacteria and the types of bacterial open reading frames in human milk that may influence bacterial establishment and stability in this primal food matrix. The human milk metagenome was also compared to that of breast-fed and formula-fed infants’ feces (n = 5, each) and mothers’ feces (n = 3) at the phylum level and at a functional level using open reading frame abundance. Additionally, immune-modulatory bacterial-DNA motifs were also searched for within human milk. Results The bacterial community in human milk contained over 360 prokaryotic genera, with sequences aligning predominantly to the phyla of Proteobacteria (65%) and Firmicutes (34%), and the genera of Pseudomonas (61.1%), Staphylococcus (33.4%) and Streptococcus (0.5%). From assembled human milk-derived contigs, 30,128 open reading frames were annotated and assigned to functional categories. When compared to the metagenome of infants’ and mothers’ feces, the human milk metagenome was less diverse at the phylum level, and contained more open reading frames associated with nitrogen metabolism, membrane transport and stress response (P < 0.05). The human milk metagenome also contained a similar occurrence of immune-modulatory DNA motifs to that of infants’ and mothers’ fecal metagenomes. Conclusions Our results further expand the complexity of the human milk metagenome and enforce the benefits of human milk ingestion on the microbial colonization of the infant gut and immunity. Discovery of immune-modulatory motifs in the metagenome of human milk indicates more exhaustive analyses of the functionality of the human milk metagenome are warranted.
    BMC Microbiology 05/2013; 13(1):116. DOI:10.1186/1471-2180-13-116 · 2.73 Impact Factor
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