Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants.

backgroundLactoferrin, a normal component of human colostrum, milk, tears and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates.

objectivesTo assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NEC in preterm neonates. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE and PREMEDLINE (1966 to Oct 2009), EMBASE (1980 to Oct 2009) and CINAHL (1982 to Oct 2009) were searched. Ongoing trials at www.clinicaltrials.gov and www.controlled-trials.com were searched. Conference proceedings of Pediatric Academic Societies (American Pediatric Society, Society for Pediatric Research and European Society for Pediatric Research) were searched for abstracts 1990 from the journal 'Pediatric Research' and 'Abstracts Online'. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials evaluating oral lactoferrin at any dose or duration for the prophylaxis of sepsis or NEC in preterm neonates. DATA COLLECTION AND ANALYSIS: Data collection and analysis were performed according to the standard methods of the CNRG. MAIN

resultsOne trial (Manzoni 2008) that randomized 472 very low birth weight infants was eligible. A statistically significant reduction in late-onset sepsis was observed in the groups that received either lactoferrin alone (RR 0.34, 95% CI 0.17, 0.70; RD -0.11, 95% CI -0.18, -0.05; NNT 9, 95% CI 5, 20) or in combination with Lactobacillus rhamnosus GG (RR 0.27, 95% CI 0.12, 0.60; RD -0.13, 95% CI -0.19, -0.06; NNT 8, 95% CI 5, 17).In subgroup analyses, infants weighing less than 1000 g and those fed exclusively on maternal milk had significant reduction in late-onset sepsis after oral lactoferrin supplementation alone. In the group supplemented with oral lactoferrin and Lactobacillus rhamnosus, infants weighing less than 1000 g had a significant reduction in late-onset sepsis, but not exclusively maternal milk fed infants.Prophylaxis with oral lactoferrin alone did not reduce the incidence of NEC (RR 0.33, 95% CI 0.09, 1.17; RD -0.04, 95% CI -0.08, 0.00), but a significant reduction in NEC with combination of lactoferrin with Lactobacillus rhamnosus GG was noted (RR 0.05, 95% CI 0.00, 0.90; RD -0.06, 95% CI -0.10, -0.02; NNT17, 95% CI 10, 50).No adverse effects due to lactoferrin were observed in this study. Long-term neurological outcomes were not assessed in this trial. AUTHORS'

conclusionsOral lactoferrin prophylaxis reduces the incidence of late-onset sepsis in infants weighing less than 1500 g and most effective in infants weighing less than 1000 g. There is no evidence of efficacy of oral lactoferrin (given alone) in the prevention of NEC in preterm neonates.Well designed, randomized trials should address dosing, duration, type of lactoferrin (bovine or human) prophylaxis in prevention of sepsis and NEC. The effect of exclusive maternal milk feeding should be clarified.