Randomized Control Trial of Human Recombinant Lactoferrin: A Substudy Reveals Effects on the Fecal Microbiome of Very Low Birth Weight Infants

Sherman, Michael P.; Sherman, J. Daniel; Arcinue, Roxanne; Niklas, Victoria

doi:10.1016/j.jpeds.2016.02.074

Cited by 49 publications

(44 citation statements)

References 27 publications

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“…Finally, prevention of colonization with nosocomial epidemic strains may be achieved by modulation of the gut microflora. For example, in a recent study, lactoferrin reduced staphylococci in the gut , and breast milk has been hypothesized to be a source of less pathogenic strains competing with the more virulent ones colonizing the neonate . In light of emerging evidence of the role of gut‐colonizing CoNS in the development of LOS, studies are needed to determine how to prevent or reduce gut colonization with more pathogenic S. epidermidis strains.…”

Section: Discussionmentioning

confidence: 99%

Molecular epidemiology of Staphylococcus epidermidis in neonatal intensive care units

Soeorg

Huik

Parm

et al. 2016

APMIS

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Late-onset sepsis (LOS) in preterm neonates is increasingly reported to be associated with gut-colonizing Staphylococcus epidermidis. We aimed to describe the molecular epidemiology of S. epidermidis colonizing the gut of neonates hospitalized in two neonatal intensive care units. S. epidermidis from rectal swabs were typed by multilocus variable-number tandem-repeat analysis (MLVA), randomly chosen isolates of predominant MLVA types additionally by multilocus sequence typing. Antimicrobial susceptibility, the presence of icaA, IS256, arginine catabolic mobile element (ACME), agr type, and SCCmec type were determined. Of 276 neonates (38.4%), 106 were colonized with S. epidermidis, yielding a total of 139 isolates (62 in one unit and 77 in another unit). Of the 55 MLVA types identified, the five predominant detected in both units corresponded to sequence type (ST) 2, ST5, and ST59 or its single locus variant ST81 and formed three major MLVA clonal complexes accounting for 74.8% of all isolates. Overall, the prevalence of mecA, icaA, IS256, and ACME was 91.4%, 28.1%, 64%, and 77%, respectively. Of the mecA-positive isolates (n = 127), 43.9% carried SCCmec type IV. Of eight episodes of LOS, four were caused by ST2 and two by ST5. Preventing gut colonization with nosocomial epidemic S. epidermidis in hospitalized neonates could contribute to the prevention of LOS.

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Section: Discussionmentioning

confidence: 99%

Molecular epidemiology of Staphylococcus epidermidis in neonatal intensive care units

Soeorg

Huik

Parm

et al. 2016

APMIS

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“…Ten RCTs published in 12 reports were included. 5,[11][12][13][14][15][16][17][18][19] Three published reports 12,20,21 illustrate one multicenter RCT. The summary of included studies is provided in ►Table 1.…”

Section: Description Of Studiesmentioning

confidence: 99%

“…All trials utilized bovine lactoferrin 5,[11][12][13][14][15][16][17]19 as an intervention except Sherman et al trial 18 which utilized human 21 and the rest of data were obtained from Manzoni et al [2009]). 20 c In these trials, there were two intervention groups, one group received lactoferrin and another group received lactoferrin and probiotic, the data from lactoferrin-only intervention group were included in the meta-analysis.…”

Section: Description Of Studiesmentioning

confidence: 99%

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Lactoferrin Supplementation to Prevent Late-Onset Sepsis in Preterm Infants: A Meta-Analysis

Razak

Hussain

2019

Am J Perinatol

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Objective To systematically review and meta-analyze the role of lactoferrin supplementation to prevent late-onset sepsis (LOS) in preterm infants. Study Design Database search include PubMed, Web of Science, and Cochrane central for randomized clinical trial (RCTs). The Cochrane Grading of Recommendations Assessment, Development, and Evaluation methodology was used for summarizing the results. Results Ten RCTs involving 3,679 infants were included. Lactoferrin supplementation with or without probiotics decreased all LOS (relative risk [RR]: 0.56; 95% confidence interval [CI]: 0.36–0.86; I 2 = 58%; 10 studies; 3,470 subjects; level of evidence [LOE]: low) significantly. Similarly, lactoferrin supplementation without probiotics decreased all LOS (RR: 0.43; 95% CI: 0.29–0.62; I 2 = 0%; 8 studies; 1,209 subjects; LOE: moderate) significantly. Lactoferrin supplementation did not significantly reduce necrotizing enterocolitis (RR: 0.62; 95% CI: 0.29–1.33; I 2 = 43%; 6 studies; 3,079 subjects; LOE: low), all-cause mortality (RR: 0.74; 95% CI: 0.36–1.53; I 2 = 53%; 8 studies; 3,395 subjects; LOE: very low), bronchopulmonary dysplasia (RR: 1; 95% CI: 0.90–1.13; I 2 = 0%; 4 studies; 2,570 subjects; LOE: moderate), and threshold retinopathy of prematurity eligible for surgical treatment (RR: 0.61; 95% CI: 0.25–1.51; I 2 = 74%; 2 studies; 2,481 subjects; LOE: very low). Conclusion Low to moderate quality evidence suggests that lactoferrin supplementation reduces LOS in preterm infants. Further research is needed to improve the certainty in the evidence.

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“…A recombinant form of lactoferrin [talactoferrin (TLf)] was also available in the US and has been used within an RCT as prophylaxis against infection, showing a reduction in fecal staphylococci load to almost undetectable levels in infants receiving TLf, and an associated reduction in coagulase-negative staphylococci infections. The authors also demonstrated a TLf-modulated reduction in fecal Enterobacteriaceae postulating that this may be a possible mechanism for a reduction in NEC since proteobacteria have been associated with NEC development (47). …”

Section: Scientific Backgroundmentioning

confidence: 99%

Mechanisms Affecting the Gut of Preterm Infants in Enteral Feeding Trials

et al. 2017

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Large randomized controlled trials (RCTs) in preterm infants offer unique opportunities for mechanistic evaluation of the risk factors leading to serious diseases, as well as the actions of interventions designed to prevent them. Necrotizing enterocolitis (NEC) a serious inflammatory gut condition and late-onset sepsis (LOS) are common feeding and nutrition-related problems that may cause death or serious long-term morbidity and are key outcomes in two current UK National Institutes for Health Research (NIHR) trials. Speed of increasing milk feeds trial (SIFT) randomized preterm infants to different rates of increases in milk feeds with a primary outcome of survival without disability at 2 years corrected age. Enteral lactoferrin in neonates (ELFIN) randomizes infants to supplemental enteral lactoferrin or placebo with a primary outcome of LOS. This is a protocol for the mechanisms affecting the gut of preterm infants in enteral feeding trials (MAGPIE) study and is funded by the UK NIHR Efficacy and Mechanistic Evaluation programme. MAGPIE will recruit ~480 preterm infants who were enrolled in SIFT or ELFIN. Participation in MAGPIE does not change the main trial protocols and uses non-invasive sampling of stool and urine, along with any residual resected gut tissue if infants required surgery. Trial interventions may involve effects on gut microbes, metabolites (e.g., short-chain fatty acids), and aspects of host immune function. Current hypotheses suggest that NEC and/or LOS are due to a dysregulated immune system in the context of gut dysbiosis, but mechanisms have not been systematically studied within large RCTs. Microbiomic analysis will use next-generation sequencing, and metabolites will be assessed by mass spectrometry to detect volatile organic and other compounds produced by microbes or the host. We will explore differences between disease cases and controls, as well as exploring the actions of trial interventions. Impacts of this research are multiple: translation of knowledge of mechanisms promoting gut health may explain outcomes or suggest alternate strategies to improve health. Results may identify new non-invasive diagnostic or monitoring techniques, preventative or treatment strategies for NEC or LOS, or provide data useful for risk stratification in future studies. Mechanistic evaluation might be especially informative where there are not clear effects on the primary outcome (ISRCTN 12554594).

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Randomized Control Trial of Human Recombinant Lactoferrin: A Substudy Reveals Effects on the Fecal Microbiome of Very Low Birth Weight Infants

Abstract: ClinicalTrials.gov: NCT00854633.

Cited by 49 publications

References 27 publications

Molecular epidemiology of Staphylococcus epidermidis in neonatal intensive care units

Molecular epidemiology of Staphylococcus epidermidis in neonatal intensive care units

Lactoferrin Supplementation to Prevent Late-Onset Sepsis in Preterm Infants: A Meta-Analysis

Mechanisms Affecting the Gut of Preterm Infants in Enteral Feeding Trials

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