{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T22:27:50Z","timestamp":1769639270274,"version":"3.49.0"},"reference-count":68,"publisher":"National Institute for Health and Care Research","issue":"74","license":[{"start":{"date-parts":[[2018,12,1]],"date-time":"2018-12-01T00:00:00Z","timestamp":1543622400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["10\/57\/14"],"award-info":[{"award-number":["10\/57\/14"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000769","name":"University of Oxford","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\"><jats:title>Background<\/jats:title><jats:p>Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow\u2019s milk, prevents infections and associated complications.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-2\"><jats:title>Objective<\/jats:title><jats:p>To determine whether or not enteral supplementation with bovine lactoferrin (The Tatua Cooperative Dairy Company Ltd, Morrinsville, New Zealand) reduces the risk of late-onset infection (acquired &gt;\u200972 hours after birth) and other morbidity and mortality in very preterm infants.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-3\"><jats:title>Design<\/jats:title><jats:p>Randomised, placebo-controlled, parallel-group trial. Randomisation was via a web-based portal and used an algorithm that minimised for recruitment site, weeks of gestation, sex and single versus multiple births.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-4\"><jats:title>Setting<\/jats:title><jats:p>UK neonatal units between May 2014 and September 2017.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-5\"><jats:title>Participants<\/jats:title><jats:p>Infants born at &lt;\u200932 weeks\u2019 gestation and aged &lt;\u200972 hours at trial enrolment.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-6\"><jats:title>Interventions<\/jats:title><jats:p>Eligible infants were allocated individually (1\u2009:\u20091 ratio) to receive enteral bovine lactoferrin (150\u2009mg\/kg\/day; maximum 300\u2009mg\/day) or sucrose (British Sugar, Peterborough, UK) placebo (same dose) once daily from trial entry until a postmenstrual age of 34 weeks. Parents, caregivers and outcome assessors were unaware of group assignment.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-7\"><jats:title>Outcomes<\/jats:title><jats:p>Primary outcome \u2013 microbiologically confirmed or clinically suspected late-onset infection. Secondary outcomes \u2013 microbiologically confirmed infection; all-cause mortality; severe necrotising enterocolitis (NEC); retinopathy of prematurity (ROP); bronchopulmonary dysplasia (BPD); a composite of infection, NEC, ROP, BPD and mortality; days of receipt of antimicrobials until 34 weeks\u2019 postmenstrual age; length of stay in hospital; and length of stay in intensive care, high-dependency and special-care settings.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-8\"><jats:title>Results<\/jats:title><jats:p>Of 2203 enrolled infants, primary outcome data were available for 2182 infants (99%). In the intervention group, 316 out of 1093 (28.9%) infants acquired a late-onset infection versus 334 out of 1089 (30.7%) infants in the control group [adjusted risk ratio (RR) 0.95, 95% confidence interval (CI) 0.86 to 1.04]. There were no significant differences in any secondary outcomes: microbiologically confirmed infection (RR 1.05, 99% CI 0.87 to 1.26), mortality (RR 1.05, 99% CI 0.66 to 1.68), NEC (RR 1.13, 99% CI 0.68 to 1.89), ROP (RR 0.89, 99% CI 0.62 to 1.28), BPD (RR 1.01, 99% CI 0.90 to 1.13), or a composite of infection, NEC, ROP, BPD and mortality (RR 1.01, 99% CI 0.94 to 1.08). There were no differences in the number of days of receipt of antimicrobials, length of stay in hospital, or length of stay in intensive care, high-dependency or special-care settings. There were 16 reports of serious adverse events for infants in the lactoferrin group and 10 for infants in the sucrose group.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-9\"><jats:title>Conclusions<\/jats:title><jats:p>Enteral supplementation with bovine lactoferrin does not reduce the incidence of infection, mortality or other morbidity in very preterm infants.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-10\"><jats:title>Future work<\/jats:title><jats:p>Increase the precision of the estimates of effect on rarer secondary outcomes by combining the data in a meta-analysis with data from other trials. A mechanistic study is being conducted in a subgroup of trial participants to explore whether or not lactoferrin supplementation affects the intestinal microbiome and metabolite profile of very preterm infants.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-11\"><jats:title>Trial registration<\/jats:title><jats:p>Current Controlled Trials ISRCTN88261002.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-12\"><jats:title>Funding<\/jats:title><jats:p>This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in<jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 22, No. 74. See the NIHR Journals Library website for further project information. This trial was also sponsored by the University of Oxford, Oxford, UK. The funder provided advice and support and monitored study progress but did not have a role in study design or data collection, analysis and interpretation.<\/jats:p><\/jats:sec>","DOI":"10.3310\/hta22740","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T09:58:36Z","timestamp":1545386316000},"page":"1-60","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Enteral lactoferrin to prevent infection for very preterm infants: the ELFIN RCT"],"prefix":"10.3310","volume":"22","clinical-trial-number":[{"clinical-trial-number":"isrctn88261002","registry":"10.18810\/isrctn","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3386-8100","authenticated-orcid":true,"given":"James","family":"Griffiths","sequence":"first","affiliation":[{"name":"National Perinatal Epidemiology Unit, University of Oxford, Oxford, 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