Prophylactic lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis in preterm infants

He, Yi; Cao, Luying; Yu, Jialin

doi:10.1097/md.0000000000011976

Cited by 48 publications

(27 citation statements)

References 29 publications

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“…A Cochrane Review of six, small, randomized control trials (RCT) that provided lactoferrin supplementation to enteral feeds found decreased late-onset bacterial and fungal sepsis in preterm infants, although the evidence was identified as low in quality [16]. A systematic review and meta-analysis reviewed nine RCTs and showed that prophylactic lactoferrin significantly reduced the incidence of late-onset sepsis and NEC (Bell's stage II or greater) [17]. Most recently, a large randomized control trial of 2203 infants contrasted these prior findings, demonstrating that enteral supplementation with bovine lactoferrin did not reduce NEC or the incidence of infection or mortality [18].…”

Section: Lactoferrinmentioning

confidence: 99%

A Review of the Immunomodulating Components of Maternal Breast Milk and Protection Against Necrotizing Enterocolitis

2019

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Breast milk contains immunomodulating components that are beneficial to newborns during maturation of their immune system. Human breast milk composition is influenced by an infant’s gestational and chronological age, lactation stage, and the mother and infant’s health status. Major immunologic components in human milk, such as secretory immunoglobulin A (IgA) and growth factors, have a known role in regulating gut barrier integrity and microbial colonization, which therefore protect against the development of a life-threatening gastrointestinal illness affecting newborn infants called necrotizing enterocolitis (NEC). Breast milk is a known protective factor in the prevention of NEC when compared with feeding with commercial formula. Breast milk supplements infants with human milk oligosaccharides, leukocytes, cytokines, nitric oxide, and growth factors that attenuate inflammatory responses and provide immunological defenses to reduce the incidence of NEC. This article aims to review the variety of immunomodulating components in breast milk that protect the infant from the development of NEC.

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Section: Lactoferrinmentioning

confidence: 99%

A Review of the Immunomodulating Components of Maternal Breast Milk and Protection Against Necrotizing Enterocolitis

2019

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“…Laktoferrin ist ein in der Muttermilch enthaltenes Glykoprotein mit immunmodulatorischen Eigenschaften. He et al kamen in einem systematischenReviewderbisdahinveröffentlichtenrandomisierten Studien mit insgesamt 1834 Patienten zum Ergebnis, dass die oraleGabevonLaktoferrineinesignifikanteReduktionderKulturpositiven LOS, der NEC und der Mortalität durch Infektionen bewirkte [136]. Allerdings waren die in diesem Review eingeschlossenen Studien u. a. hinsichtlich der Inzidenz der Pilzsepsis sehr heterogen.IndernachdemReviewvonHeetal.veröffentlichten ELFIN Studie mit 2.203 Patienten hatte die Gabe von bovinem Lak-toferrinkeinenEinflussaufdasRisikoderLOS(RR0,95;95%CI0,86-1,04; p = 0,233) [137,138].…”

Section: Prävention Der Los Durch Laktoferrinunclassified

Bakterielle Infektionen bei Neugeborenen. Leitlinie der GNPI, DGPI, DGKJ und DGGG. (S2k-Level, AWMF-Leitlinien-Register-Nr. 024/008, April 2018)

Zemlin

Berger²,

Franz

et al. 2019

Z Geburtshilfe Neonatol

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“…Lactoferrin is an important protein consumed by breast-fed new born infants, with the highest concentration in colostrum (range 6-7 g/L) and a relatively lower concentration in mature milk (range 1-5 g/L). 2 As a multifunctional protein protective against infection and inflammation, lactoferrin has been used as a supplement for human infant formula. 3 Lactoferrin is also present in bovine milk at a concentration of 0.2 to 1.5 g/L with over 70% amino acid homology compared to human lactoferrin.…”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10] Though several studies investigated multiple aspects of lactoferrin function, the underlying mechanism of its protective effect during NEC progression remains unclear, and its protective effects on the early stages of NEC is still controversial. 2,11 Therefore, we sought to elucidate the mechanisms driving lactoferrinmediated protection during NEC progression, especially focused on its regulation of inflammation and cell proliferation. Furthermore, we administered lactoferrin on healthy pup mice to verify its safety and test for adverse effects.…”

Section: Introductionmentioning

confidence: 99%

Lactoferrin Reduces Necrotizing Enterocolitis Severity by Upregulating Intestinal Epithelial Proliferation

Liu

Zhu

et al. 2019

Eur J Pediatr Surg

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Introduction Necrotizing enterocolitis (NEC) is a devastating intestinal illness in premature infants characterized by severe intestinal inflammation. Despite medical interventions, NEC mortality remains alarmingly high, which necessitates improved therapies. Lactoferrin is among the most abundant proteins in human milk and has important immunomodulatory functions. While previous studies have indicated protective effects of lactoferrin against neonatal sepsis and NEC, the underlying mechanism remains unclear. We hypothesize that lactoferrin downregulates inflammation and upregulates proliferation in intestinal epithelium during NEC injury. Materials and Methods NEC was induced by hypoxia, gavage feeding of hyperosmolar formula and lipopolysaccharide between postnatal day P5 and P9 (n = 8). Breastfed mice were used as control (n = 7). Lactoferrin (0.3 g/kg/day) was administered once daily by gavage from P6 to P8 in both NEC (NEC + Lac; n = 9) and control mice (Cont + Lac; n = 5). Distal ileum was harvested on P9 and analyzed for disease severity, inflammation, and proliferation. Groups were compared using one-way ANOVA and t-test appropriately; p < 0.05 was considered significant. Results Compared to NEC group, lactoferrin-treated NEC mice had reduced disease severity, reduced inflammation markers IL-6 and TNF-α expression and increased intestinal stem cell marker Lgr5 + expression. Lactoferrin-treated NEC mice exhibited increased nuclear β-catenin, indicating upregulated Wnt pathway, and increased Ki67 positivity, suggesting enhanced proliferation. Furthermore, lactoferrin administration to control mice did not affect intestinal inflammation as well as Lgr5 + stem cell expression and epithelial proliferation. This supports the safety of lactoferrin administration and indicates that the beneficial effects of lactoferrin are present when intestinal injury such as NEC is present. Conclusion Lactoferrin administration reduces the intestinal injury in experimental NEC by downregulating inflammation and upregulating cell proliferation. This beneficial effect of lactoferrin in stimulating cell proliferation is mediated by the Wnt pathway. This experimental study provides insights on the mechanism of action of lactoferrin in NEC and the role of lactoferrin in enteral feeding.

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Prophylactic lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis in preterm infants

Abstract: Current evidence indicates that lactoferrin could significantly reduce the incidence of NEC and LOS, and decrease the risk of hospital-acquired infection and infection-related mortality in premature infants without obvious adverse effects.

Cited by 48 publications

References 29 publications

A Review of the Immunomodulating Components of Maternal Breast Milk and Protection Against Necrotizing Enterocolitis

A Review of the Immunomodulating Components of Maternal Breast Milk and Protection Against Necrotizing Enterocolitis

Bakterielle Infektionen bei Neugeborenen. Leitlinie der GNPI, DGPI, DGKJ und DGGG. (S2k-Level, AWMF-Leitlinien-Register-Nr. 024/008, April 2018)

Lactoferrin Reduces Necrotizing Enterocolitis Severity by Upregulating Intestinal Epithelial Proliferation

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