Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial.
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.
Manzoni
Paolo
P
Neonatology and Neonatal Intensive Care Unit, S. Anna Hospital, Azienda Ospedaliera Regina Margherita-S. Anna, C. Spezia 60, 10126 Torino, Italy. paolomanzoni@hotmail.com
Rinaldi
Matteo
M
Cattani
Silvia
S
Pugni
Lorenza
L
Romeo
Mario Giovanni
MG
Messner
Hubert
H
Stolfi
Ilaria
I
Decembrino
Lidia
L
Laforgia
Nicola
N
Vagnarelli
Federica
F
Memo
Luigi
L
Bordignon
Linda
L
Saia
Onofrio Sergio
OS
Maule
Milena
M
Gallo
Elena
E
Mostert
Michael
M
Magnani
Cristiana
C
Quercia
Michele
M
Bollani
Lina
L
Pedicino
Roberto
R
Renzullo
Livia
L
Betta
Pasqua
P
Mosca
Fabio
F
Ferrari
Fabrizio
F
Magaldi
Rosario
R
Stronati
Mauro
M
Farina
Daniele
D
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*
D007781:Lactoferrin