title: Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial.
abstract: BACKGROUND
  Sepsis is a common and severe complication in premature neonates, particularly those with very low birth weight (VLBW) (<1500 g). Whether lactoferrin, a mammalian milk glycoprotein involved in innate immune host defenses, can reduce the incidence of sepsis is unknown. In animal models, the probiotic Lactobacillus rhamnosus GG (LGG) enhances the activity of lactoferrin but has not been studied in human infants.
  
  
  OBJECTIVE
  To establish whether bovine lactoferrin (BLF), alone or in combination with LGG, reduces the incidence of late-onset sepsis in VLBW neonates.
  
  
  METHODS
  Prospective, multicenter, double-blind, placebo-controlled, randomized trial conducted in 11 Italian tertiary neonatal intensive care units. Patients were 472 VLBW infants enrolled from October 1, 2007, through July 31, 2008, and assessed until discharge for development of sepsis.
  
  
  METHODS
  Infants were randomly assigned to receive orally administered BLF (100 mg/d) alone (n = 153), BLF plus LGG (6 x 10(9) colony-forming units/d) (n = 151), or placebo (n = 168) from birth until day 30 of life (day 45 for neonates <1000 g at birth).
  
  
  METHODS
  First episode of late-onset sepsis, ie, sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid.
  
  
  RESULTS
  Demographic, clinical, and management characteristics of the 3 groups were similar, including type of feeding and intake of maternal milk. Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups (9/153 [5.9%] and 7/151 [4.6%], respectively) than in the control group receiving placebo (29/168 [17.3%]) (risk ratio, 0.34; 95% confidence interval, 0.17-0.70; P = .002 for BLF vs control and risk ratio, 0.27; 95% confidence interval, 0.12-0.60; P < .001 for BLF plus LGG vs control). The decrease occurred for both bacterial and fungal sepsis. No adverse effects or intolerances to treatment occurred.
  
  
  CONCLUSIONS
  Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates.
  
  
  BACKGROUND
  isrctn.org Identifier: ISRCTN53107700.
authors.affiliation: Neonatology and Neonatal Intensive Care Unit, S. Anna Hospital, Azienda Ospedaliera Regina Margherita-S. Anna, C. Spezia 60, 10126 Torino, Italy. paolomanzoni@hotmail.com
authors.forename: Paolo
authors.initials: P
authors.lastname: Manzoni
authors.forename: Matteo
authors.initials: M
authors.lastname: Rinaldi
authors.forename: Silvia
authors.initials: S
authors.lastname: Cattani
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pugni
authors.forename: Mario Giovanni
authors.initials: MG
authors.lastname: Romeo
authors.forename: Hubert
authors.initials: H
authors.lastname: Messner
authors.forename: Ilaria
authors.initials: I
authors.lastname: Stolfi
authors.forename: Lidia
authors.initials: L
authors.lastname: Decembrino
authors.forename: Nicola
authors.initials: N
authors.lastname: Laforgia
authors.forename: Federica
authors.initials: F
authors.lastname: Vagnarelli
authors.forename: Luigi
authors.initials: L
authors.lastname: Memo
authors.forename: Linda
authors.initials: L
authors.lastname: Bordignon
authors.forename: Onofrio Sergio
authors.initials: OS
authors.lastname: Saia
authors.forename: Milena
authors.initials: M
authors.lastname: Maule
authors.forename: Elena
authors.initials: E
authors.lastname: Gallo
authors.forename: Michael
authors.initials: M
authors.lastname: Mostert
authors.forename: Cristiana
authors.initials: C
authors.lastname: Magnani
authors.forename: Michele
authors.initials: M
authors.lastname: Quercia
authors.forename: Lina
authors.initials: L
authors.lastname: Bollani
authors.forename: Roberto
authors.initials: R
authors.lastname: Pedicino
authors.forename: Livia
authors.initials: L
authors.lastname: Renzullo
authors.forename: Pasqua
authors.initials: P
authors.lastname: Betta
authors.forename: Fabio
authors.initials: F
authors.lastname: Mosca
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ferrari
authors.forename: Rosario
authors.initials: R
authors.lastname: Magaldi
authors.forename: Mauro
authors.initials: M
authors.lastname: Stronati
authors.forename: Daniele
authors.initials: D
authors.lastname: Farina
mesh_terms: D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000401:mortality / Q000517:prevention & control*; D019102:Infant, Very Low Birth Weight; D015931:Intensive Care, Neonatal; D052201:Lacticaseibacillus rhamnosus; D007781:Lactoferrin / Q000008:administration & dosage*; D016015:Logistic Models; D008297:Male; D019936:Probiotics / Q000627:therapeutic use*; D012307:Risk Factors; D018805:Sepsis / Q000401:mortality / Q000517:prevention & control*
chemical_list: D007781:Lactoferrin