Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates.

BACKGROUND: Neonatal sepsis and necrotizing enterocolitis (NEC) cause significant neonatal mortality and morbidity in spite of appropriate antibiotic therapy. Enhancing host defence and modulating inflammation by using lactoferrin as an adjunct to antibiotics in the treatment of sepsis and/or NEC may improve clinical outcomes.

OBJECTIVES: The primary objective is to assess safety and efficacy of oral lactoferrin as an adjunct to antibiotics in the treatment of neonates with suspected or confirmed sepsis and/or NEC.

SEARCH STRATEGY: Relevant trials in any language were searched in June 2008 in the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (1966 - June 2008), PREMEDLINE, EMBASE (1980 - June 2008), CINAHL (1982 - June 2008), web sites: www.clinicaltrials.gov and www.controlled-trials.com, abstracts from the annual meeting of Pediatric Academic Societies (1990- June 2008), by contacting authors who have published in this field, from the reference lists of identified clinical trials and in the reviewer's personal files.

SELECTION CRITERIA: Randomized or quasi-randomized controlled trials evaluating oral lactoferrin (at any dose or duration) used as an adjunct to antibiotic therapy compared with antibiotic therapy alone (with or without placebo) or other adjuncts to antibiotic therapy to treat neonates at any gestational age up to 44 weeks postmenstrual age with confirmed or suspected sepsis or necrotizing enterocolitis (Bell's Stage II or III).

DATA COLLECTION AND ANALYSIS: We used the standardized methods of the Cochrane Neonatal Review Group (CNRG) for conducting a systematic review and for assessing the methodological quality of the studies (https://neonatal.cochrane.org/en/index.html). The titles and the abstracts of studies identified by the search strategy were independently assessed by the two review authors and full text version was obtained for assessment if necessary. Forms were designed for trial inclusion/exclusion and data extraction.

MAIN RESULTS: Our search strategy did not identify any eligible trials or potentially eligible ongoing neonatal trials. One trial was excluded and three ongoing or soon to be started adult trials using lactoferrin for the treatment of infections were identified.

IMPLICATIONS FOR PRACTICE: Currently there is no evidence to recommend or refute the use of lactoferrin for the treatment of neonatal sepsis or necrotizing enterocolitis as an adjunct to antibiotic therapy.

IMPLICATIONS FOR RESEARCH: The safety and efficacy of different preparations and doses of lactoferrin needs to be established in neonates. Well designed adequately powered randomized multicenter trials are needed to address the efficacy and safety of lactoferrin in the treatment of neonatal sepsis and necrotizing enterocolitis. These trials should evaluate long-term neurodevelopmental and pulmonary outcomes in addition to short-term outcomes (e.g. mortality).