This Article  • Full text  • PDF  • eTables  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in JAMA  Topic Collections  • Bacterial Infections  • Critical Care/ Intensive Care Medicine  • Pediatric/ Neonatal Critical Care  • Pediatrics  • Neonatology and Infant Care  • Randomized Controlled Trial  • Immunology  • Immunology, Other  • Infectious Diseases  • Alert me on articles by topic  Social Bookmarking   What's this?

A Randomized Trial

Paolo Manzoni, MD; Matteo Rinaldi, MD; Silvia Cattani, MD; Lorenza Pugni, MD; Mario Giovanni Romeo, MD; Hubert Messner, MD; Ilaria Stolfi, MD; Lidia Decembrino, MD; Nicola Laforgia, MD; Federica Vagnarelli, MD; Luigi Memo, MD; Linda Bordignon, MD; Onofrio Sergio Saia, MD; Milena Maule, PhD, MSc, BSc; Elena Gallo, MD; Michael Mostert, MD; Cristiana Magnani, MD; Michele Quercia, MD; Lina Bollani, MD; Roberto Pedicino, MD; Livia Renzullo, MD; Pasqua Betta, MD; Fabio Mosca, MD, PhD; Fabrizio Ferrari, MD, PhD; Rosario Magaldi, MD; Mauro Stronati, MD; Daniele Farina, MD; for the Italian Task Force for the Study and Prevention of Neonatal Fungal Infections, the Italian Society of Neonatology

JAMA. 2009;302(13):1421-1428.

Context  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.

Design, Setting, and Patients  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.

Intervention  Infants were randomly assigned to receive orally administered BLF (100 mg/d) alone (n = 153), BLF plus LGG (6 x 10⁹ 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).

Main Outcome Measure  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.

Conclusion  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.

Trial Registration  isrctn.org Identifier: ISRCTN53107700

Author Affiliations: Neonatal Intensive Care Unit (NICU), S. Anna Hospital, Torino (Drs Manzoni, Gallo, and Farina); NICU, Ospedali Riuniti, Foggia (Drs Rinaldi and Magaldi); NICU, University of Modena, Modena (Drs Cattani and Ferrari); NICU, IRCCS Mangiagalli Hospital, Milano (Drs Pugni and Mosca); NICU, Azienda Ospedaliera Universitaria Policlinico, Catania (Drs Romeo and Betta); NICU, Ospedale Regionale, Bolzano (Drs Messner and Renzullo); NICU, Policlinico Umberto I, Rome (Drs Stolfi and Pedicino); NICU, IRCCS San Matteo, Pavia (Drs Decembrino, Bollani, and Stronati); NICU, Policlinico University Hospital, Bari (Drs Laforgia and Quercia); NICU, Arcispedale S. M. Nuova, Reggio Emilia (Drs Vagnarelli and Magnani); NICU, Ca’ Foncello Hospital, Treviso (Drs Memo, Bordignon, and Saia); Departments of Biomedical Sciences and Human Oncology, Cancer Epidemiology Unit, University of Torino, Torino (Dr Maule); and Department of Pediatrics, University of Torino, Torino (Dr Mostert), Italy.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

Lactoferrin Supplementation to Prevent Nosocomial Infections in Preterm Infants
David A. Kaufman
JAMA. 2009;302(13):1467-1468.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Lactoferrin and Sepsis: Good News for Low Birth Weight Infants
JWatch Pediatrics 2009;2009:1-1.
FULL TEXT  

Lactoferrin Supplementation to Prevent Nosocomial Infections in Preterm Infants
Kaufman
JAMA 2009;302:1467-1468.
FULL TEXT