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Lactoferrin and Sepsis: Good News for Low Birth Weight Infants

Lactoferrin reduced the incidence of late-onset sepsis in neonates.

Sepsis continues to be a major cause of death and developmental morbidity among very low birth weight (VLBW) infants (<1500 g). Investigators examined whether lactoferrin — the principal protein in human colostrum — reduces the incidence of late-onset sepsis in VLBW infants. In a prospective double-blind study, researchers randomly assigned 472 infants from 11 neonatal intensive care units in Italy in 2007–2008 to receive orally administered bovine lactoferrin (BLF), BLF plus the probiotic Lactobacillus rhamnosus GG (BLF+LGG), or placebo for 30 days.

Overall, 45 infants had a first episode of late-onset sepsis (occurring >72 hours after birth), with 56 causative isolates. The incidence of sepsis was significantly lower in the BLF and BLF+LGG groups compared with the placebo group (5.9% and 4.6% vs. 17.3%). When infants were stratified by birth weight, extremely low birth weight (ELBW) infants (<1000 g) in both treatment groups, but not infants with birth weights of 1001 to 1500 g, had significantly lower incidence of sepsis. When the two treatment groups were combined, the incidence of sepsis was significantly reduced for both ELBW infants and those with birth weights of 1001 to 1500 g. Death from sepsis also was reduced in both treatment groups compared with placebo (0% and 0.7% vs. 4.8%). Compared with placebo, BLF+LGG significantly reduced necrotizing enterocolitis, and BLF significantly reduced threshold retinopathy of prematurity. No other secondary outcomes differed significantly, and no adverse effects were reported. The authors conclude that BLF supplements, either alone or with LGG, reduce the incidence of late-onset sepsis in VLBW infants.

THE Journal Watch PEDIATRICS AND ADOLESCENT MEDICINE PERSPECTIVE

Obviously, new data such as these must be substantiated in other studies. If the results stand the test of time — and safety and efficacy are confirmed — as a neonatologist, I believe that this study will prove to be a landmark in the annals of infant care. These findings are very exciting, especially if we find that the use of lactoferrin also leads to improved neurodevelopmental outcomes.

— William P. Kanto, Jr., MD

THE Journal Watch INFECTIOUS DISEASES PERSPECTIVE

These findings are consistent with a large body of basic science observations. Lactoferrin is a major component of the innate immune system and is present in high concentrations in milk, mucosal secretions, and neutrophil granules. In vitro studies have shown that the whole protein has broad antimicrobial activity against gram-negative bacteria and can promote intestinal cell proliferation. Additionally, exposure of BLF to pepsin (e.g., in gastric secretions) releases a peptide fragment that is bactericidal in vitro for gram-positive and gram-negative bacteria and yeast. As noted, these observations need to be replicated in other trials and, if confirmed, extended to other neonatal and immunosuppressed populations.

— Richard T. Ellison III, MD

Manzoni P et al. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: A randomized trial. JAMA 2009 Oct 7 ; 302:1421.

• Original article (Subscription may be required)
• Medline abstract (Free)

Kaufman DA. Lactoferrin supplementation to prevent nosocomial infections in preterm infants. JAMA 2009 Oct 7 ; 302:1467.

• Original article (Subscription may be required)
• Medline abstract (Free)

— William P. Kanto, Jr., MD, and Richard T. Ellison III, MD

Published in Journal Watch Pediatrics and Adolescent Medicine October 14, 2009