Enteral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates

Review question

Is lactoferrin supplementation, along with antibiotics, effective and safe for babies with sepsis and necrotizing enterocolitis?


Newborn babies, especially those born preterm, are at risk from infections in the blood (sepsis), gastrointestinal inflammation and injury (necrotizing enterocolitis), or both these conditions. A number of babies with sepsis or necrotizing enterocolitis die or suffer from long-term brain and lung damage, despite treatment with antibiotics. Lactoferrin, a substance normally present in human milk, may be effective against infections and gastrointestinal injury.

Study characteristics

We searched for studies that used lactoferrin supplementation feeds to treat babies with infection or gastrointestinal injury.

Key results

We did not find any studies on lactoferrin supplementation with antibiotics in treating babies with sepsis and necrotizing enterocolitis. It is unlikely that lactoferrin will be used for treatment of infection or intestinal inflammation in preterm babies because it has not been found effective to prevent these illnesses. During infection and intestinal problems feeds are usually not given. We do not recommend studies be done in the future to address this issue.

Quality of evidence

This could not be assessed as no eligible studies were identified.

Authors' conclusions: 

Implications for practice: currently there is no evidence to support or refute the use of enteral lactoferrin, as an adjunct to antibiotic therapy, for the treatment of neonatal sepsis or necrotizing enterocolitis.

Implications for research: given the lack of efficacy of enteral lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis, evaluation of enteral lactoferrin as an adjunctive agent for treatment of sepsis or necrotizing enterocolitis does not appear to be a research priority.

Read the full abstract...

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


The primary objective was to assess safety and efficacy of oral lactoferrin as an adjunct to antibiotics in the treatment of neonates with suspected or confirmed sepsis, NEC, or both.

Search strategy: 

We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 9), MEDLINE via PubMed, PREMEDLINE, (1966 to 20 September 2018) Embase (1980 to 20 September 2018), and CINAHL (1982 to 20 September 2018). We also searched clinical trial databases, conference proceedings, the reference lists of retried articles and clinical trials, and the authors' personal files.

Selection criteria: 

We included randomized or quasi-randomized controlled trials evaluating enteral 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 Cochrane Neonatal for conducting a systematic review and for assessing the methodological quality of studies (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 versions were obtained for assessment if necessary. Forms were designed to record trial inclusion/exclusion and data extraction. We used the GRADE approach to assess the quality of evidence.

Main results: 

We did not identify any eligible trials evaluating lactoferrin for the treatment of neonatal sepsis or NEC.