Bovine lactoferrin appears to decrease the incidence of sepsis in very low–birth weight infants
Article Outline
- Question
- Design
- Setting
- Participants
- Intervention
- Outcomes
- Main Results
- Conclusion
- Commentary
- References
- Copyright
Manzoni P, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H, et al. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth–weight neonates: a randomized trial. JAMA 2009;302:1421-8.
Question
Among very low–birth weight (VLBW) (<1500 g) infants, does bovine lactoferrin (BLF), alone or in combination with Lactobacillus rhamnosus GG (LGG), reduce the incidence of late-onset sepsis?
Design
Multicenter, double-blind, placebo-controlled, randomized trial.
Setting
Eleven Italian tertiary neonatal intensive care units.
Participants
A total of 472 VLBW infants enrolled from October 1, 2007, through July 31, 2008.
Intervention
Infants were randomly assigned to receive orally administered BLF (100 mg/d) alone (n = 153), BLF plus LGG (6 × 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).
Outcomes
First episode of late-onset sepsis, that is, sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid.
Main 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 + 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; number needed to treat [NNT] = 9 for BLF vs control and risk ratio, 0.27; 95% confidence interval, 0.12-0.60; P < .001; NNT = 8 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.
Commentary
Although these results are encouraging, the authors are appropriately cautious about the generalizability of their results, the potential for adverse effects in larger populations, and whether the study doses of BLF and LGG were optimal. It is acknowledged that the use of a single standard dose, not normalized for weight or surface area, may explain the improved benefit suggested in the smaller infants. It would be useful to know how many of the positive cultures were recovered from peritoneal fluid because contamination from necrotic bowel at >3 days of age would not be surprising and the underlying mechanism for the bowel necrosis may or may not be unrelated to the luminal content (including BLF and/or LGG). Cessation of follow-up at discharge from the neonatal intensive care unit may prove to be the greatest limitation of this study. The major mechanisms by which lactoferrin achieves antimicrobial activity continue to be elucidated, but definitely include iron binding (with consequent lack of availability to microbes and host tissues) and may also involve disruption of microbial cell membranes and modulation of inflammatory responses.1, 2 It has been demonstrated previously by numerous investigators that insufficient iron in early life (fetal and neonatal) may have significant long-term effects on brain development, as well as behavioral and cognitive outcome. Long-term follow-up is essential to determine whether the dose of BLF used is sufficient to have neurodevelopmental consequences and whether potential disruption of bowel colonization may predispose to enteric morbidity later in childhood.
References
PII: S0022-3476(10)00196-4
doi:10.1016/j.jpeds.2010.02.052
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