The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): a multicentre, double-blind, randomised controlled trial

Tarnow‐Mordi, William; Abdellatif, Mohamed; Martin, Andrew; Pammi, Mohan; Robledo, Kristy; Manzoni, Paolo; Osborn, David A; Lui, Kei; Keech, Anthony; Hague, Wendy; Ghadge, Alpana; Travadi, Javeed; Brown, Rebecca T.; Darlow, Brian A; Liley, Helen; Pritchard, Margo; Kochar, Anu; Isaacs, David; Gordon, Adrienne; Askie, Lisa; Cruz, Melinda; Schindler, Tim; Dixon, Kelly M.; Deshpande, Girish; Tracy, Mark; Schofield, Deborah; Austin, Nicola; Sinn, John; Simes, R. J.; Black, Robert A.; Nie, Wei-Zhi; Reid, Sharon; Michalowski, Joanna; McKeown, Lisa; Koorts, Pieter; Broom, Margaret; Kwan, P.; Morris, Scott; Cornthwaite, Katie; Tobiansky, Rodney; D’Arcy, Deirdre M.; Goodchild, Louise; Collins, Cleve B.; Noble, Emma; Lewis, Angela N.; Yeomans, Emma; Hua, C.; Hinder, Murray; Bhaskaracharya, A.; Graham, Petra L.; Patel, Harshad; Wilkes, Nicholas J.; Marlow, Neil; Soll, Roger F.; McKinlay, Christopher J.D.; Modi, Neil; Marschner, Ian C.; Stenson, Ben J; Espinoza, David

doi:10.1016/s2352-4642(20)30093-6

Cited by 34 publications

(20 citation statements)

References 42 publications

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“…These findings are consistent with the recent report of 2 large clinical trials involving a total of 3,745 preterm infants <32 weeks GA who received enteral supplementation with 150 or 200 mg/kg daily of bovine lactoferrin or placebo from the age of <72 h until 34 weeks. Bovine lactoferrin supplementation did not reduce LOS in these adequately powered studies; a meta-analysis of 13 trials concluded that lactoferrin may reduce LOS [7, 8].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, there are no data comparing stool or blood lactoferrin or lactoferricin levels from preterm infants prior to and following enteral lactoferrin administration to demonstrate effectiveness. Recently, 2 large clinical trials in very preterm infants (ELFIN and LIFT, n = 2,203 and n = 1,542, respectively) reported no difference in LOS rates between the enteral bovine lactoferrin supplementation group and a control group [7, 8].…”

Section: Introductionmentioning

confidence: 99%

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Lactoferrin Expression Is Not Associated with Late-Onset Sepsis in Very Preterm Infants

et al. 2020

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Background: Preterm infants are at a high risk of developing late-onset sepsis (LOS). Lactoferrin is one of the most abundant endogenous antimicrobial proteins expressed in breast milk, stools, and blood, and a candidate for preventive intervention. Large clinical trials have recently investigated whether enteral supplementation with bovine lactoferrin reduces LOS. Aim: To characterize lactoferrin levels in preterm infants with and without LOS during the first month of life. Methods: Very preterm and term infants were recruited and serial biosamples collected during the first month of life. Lactoferrin levels were determined by immunoassay in cord blood and peripheral blood on days 1, 7, 14, 21, and 28; in the stools on days 1 and 28; and in the mother’s breast milk on days 7 and 21. Furthermore, we assessed the capacity of the peripheral blood to release lactoferrin in response to an in vitro challenge with live Staphylococcus epidermidis, lipopolysaccharide, and fibroblast-stimulating lipopeptide 1. Results: Plasma lactoferrin levels were higher in cord blood and day 1 peripheral blood and declined during the first month of life. Plasma lactoferrin levels were similar in term infants and in preterm infants with (n = 32) and without LOS (n = 53). S. epidermidis-induced lactoferrin levels were lower following the sepsis episode. Conclusions: Endogenous lactoferrin expression in preterm infants does not appear to affect their risk of developing LOS. These findings are in line with the lack of benefit recently observed in large trials of enteral supplementation with bovine lactoferrin to prevent LOS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lactoferrin Expression Is Not Associated with Late-Onset Sepsis in Very Preterm Infants

et al. 2020

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“…The effects of enteral lactoferrin were outside our scope as these were described very recently in systematic reviews elsewhere [ 11 , 12 , 13 ]. To summarize, enteral bovine or recombinant human lactoferrin resulted in a possibly slightly lower incidence of late-onset sepsis (studied in 5425 infants in total), but no effects were observed on NEC, mortality, or neurodevelopment [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…To date, the majority of the clinical trials regarding enteral supplementation of bioactive factors has focused on the efficacy and safety of the antimicrobial protein lactoferrin. These data have been summarized in very recently published systematic reviews [11][12][13]. The aim of this systematic review was to provide an overview and guidance of other well-known bioactive factors, which have been studied as an enteral supplement, and to provide an overview of ongoing trials.…”

Section: Introductionmentioning

confidence: 99%

Enteral Bioactive Factor Supplementation in Preterm Infants: A Systematic Review

et al. 2020

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Feeding preterm infants with mother’s own milk is associated with a reduction in postnatal complications and an improved neurocognitive outcome. Therefore, the bioactive factor composition of human milk has been used as a tool for the development of nutritional supplements with a potential prophylactic or therapeutic effect. The aim of this systematic review was to provide an overview on bioactive factors which have been studied as supplement to enteral nutrition in randomized controlled trials, and to provide an overview of ongoing trials. MEDLINE, EMBASE, CENTRAL, and clinical trial registers were searched. Studies on the antimicrobial protein lactoferrin were excluded as these were summarized very recently in three separate systematic reviews. Studies on vitamins D, K and iron were also excluded as they are already incorporated in most international guidelines. We identified 17 different bioactive factors, which were investigated in 26 studies. Despite the encouraging potential effects of several bioactive factors, more high-quality studies with a sufficient number of preterm infants are required before a certain factor may be implemented into clinical practice. Three large trials (n > 500) that investigate the effects of either enteral insulin or vitamin A are currently ongoing and could provide more definite answers on these specific supplements.

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“…Preterm infants who receive it, show a trend toward lower infectious morbidity and changes in the fecal microbiome [ 159 , 160 ]. However, more trials are needed to demonstrate the efficacy of lactoferrin supplementation for the treatment of sepsis and necrotizing enteritis in preterm infants [ 161 , 162 ]. The efficacy of recombinant human lactoferrin supplementation was also demonstrated in adults: reducing mortality in adults in intensive care due to severe sepsis [ 163 ]; increasing the efficacy of H. pylori eradication therapies [ 164 ], decreasing postantibiotic diarrhea in elderly patients [ 165 ]; increasing the efficacy of standard interferon (IFN) and ribavirin therapy in hepatitis C and other viral infections [ 166 ] or reducing the symptoms and duration of the common cold [ 167 ].…”

Section: Breast Milk Proteinsmentioning

confidence: 99%

Breast Milk: A Source of Functional Compounds with Potential Application in Nutrition and Therapy

et al. 2021

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Breast milk is an unbeatable food that covers all the nutritional requirements of an infant in its different stages of growth up to six months after birth. In addition, breastfeeding benefits both maternal and child health. Increasing knowledge has been acquired regarding the composition of breast milk. Epidemiological studies and epigenetics allow us to understand the possible lifelong effects of breastfeeding. In this review we have compiled some of the components with clear functional activity that are present in human milk and the processes through which they promote infant development and maturation as well as modulate immunity. Milk fat globule membrane, proteins, oligosaccharides, growth factors, milk exosomes, or microorganisms are functional components to use in infant formulas, any other food products, nutritional supplements, nutraceuticals, or even for the development of new clinical therapies. The clinical evaluation of these compounds and their commercial exploitation are limited by the difficulty of isolating and producing them on an adequate scale. In this work we focus on the compounds produced using milk components from other species such as bovine, transgenic cattle capable of expressing components of human breast milk or microbial culture engineering.

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The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): a multicentre, double-blind, randomised controlled trial

Cited by 34 publications

References 42 publications

Lactoferrin Expression Is Not Associated with Late-Onset Sepsis in Very Preterm Infants

Lactoferrin Expression Is Not Associated with Late-Onset Sepsis in Very Preterm Infants

Enteral Bioactive Factor Supplementation in Preterm Infants: A Systematic Review

Breast Milk: A Source of Functional Compounds with Potential Application in Nutrition and Therapy

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