Is Lactoferrin More Effective in Reducing Late-Onset Sepsis in Preterm Neonates Fed Formula Than in Those Receiving Mother's Own Milk? Secondary Analyses of Two Multicenter Randomized Controlled Trials

Background: Lactoferrin is the major antimicrobial protein in human milk. In our randomized controlled trial (RCT) of bovine lactoferrin (BLF) supplementation in preterm neonates, BLF reduced late-onset sepsis (LOS). Mother's own milk (MM) contains higher concentrations of lactoferrin than donor milk or formula, but whether BLF is more effective in infants who receive formula or donor milk is uncertain. Aim: To evaluate the incidence of LOS in preterm infants fed MM and in those fed formula and/or donor milk. Study Design: This is a (A) post hoc subgroup analysis, in our RCT of BLF, of its effects in preterm infants fed MM, with or without formula, versus those fed formula and/or donor milk (no-MM) and (B) post hoc meta-analysis, in our RCT of BLF and in the ELFIN (Enteral Lactoferrin in Neonates) RCT, of the effect of BLF in subgroups not exclusively fed MM. Results (A) Of 472 infants in our RCT, 168 were randomized to placebo and 304 were randomized to BLF. Among MM infants, LOS occurred in 22/133 (16.5%) infants randomized to placebo and in 14/250 (5.6%) randomized to BLF (relative risk or risk ratio (RR): 0.34; relative risk reduction (RRR): 0.66; 95% confidence interval (95% CI) for RR: 0.18-0.64; p < 0.0008). Among no-MM infants, LOS occurred in 7/35 (20.0%) randomized to placebo and in 2/54 (3.7%) randomized to BLF (RR: 0.19; RRR: 0.81; 95% CI for RR: 0.16-0.96; p = 0.026). In multivariable logistic regression analysis, there was no interaction between BLF treatment effect and type of feeding (p = 0.628). (B) In 1,891 infants not exclusively fed MM in our RCT of BLF and in the ELFIN RCT, BLF reduced the RR of LOS by 18% (RR: 0.82; 95% CI: 0.71-0.96; p = 0.01). Conclusion: Adequately powered studies should address the hypothesis that BLF is more effective in infants fed formula or donor milk than those fed MM. Such studies should evaluate whether a specific threshold of total lactoferrin intake can be identified to protect such patients from LOS

Bovine Lactoferrin Supplementation for Prevention of Necrotizing Enterocolitis in Preterm Very-Low-Birth-Weight Neonates : A Randomized Trial

BACKGROUND: NEC is a common and severe complication in premature neonates, particularly those with very-low-birth-weight (VLBW, <1500 g at birth). Probiotics including Lactobacillus rhamnosus GG (LGG) proved effective in preventing NEC in preterm infants in RCTs. Lactoferrin, a mammalian milk glycoprotein involved in innate immune host defenses, can reduce the incidence of NEC in animal models, and its action is enhanced by LGG. The effect on NEC of bovine lactoferrin (BLF), alone or with the probiotic LGG, has not yet been studied in human infants. OBJECTIVE: To establish whether bovine lactoferrin alone or with LGG, reduces the incidence of NEC in VLBW neonates. DESIGN/METHODS: This was an international, multicenter, randomized, double-blind, placebo-controlled trial. Thirteen Italian and New Zealand tertiary neonatal intensive care units screened and enrolled preterm, VLBW infants from October 1, 2007 through October 31, 2010. Infants were randomly assigned to receive orally either bLF (100mg/day) alone (group LF; n=251) or with LGG (at 6x109 CFU/day; group LF+LGG; n=242), or placebo (Control group; n=259) from birth until day 30 of life (45 for neonates <1000g at birth). The main outcome measures were NEC greater than stage 2, and NEC (any stage). RESULTS: 825 VLBW neonates were enrolled and assessed until discharge for development of NEC.Demographics, clinical and management characteristics of the 3 groups were similar, including type of feeding and maternal milk intakes. NEC incidence was significantly lower in groups BLF and BLF+LGG [5/251 (2.0%) and 1/242 (0.4%), respectively] than in controls [14/259 (5.4%)] (R.R. 0.35; 95% C.I. 0.13-0.99; p=0.04 for BLF vs. control; R.R 0.07; 95% C.I. 0.01-0.55; p=0.001 for BLF+LGG vs.control). The decrease occurred both for surgical and low-stages NECs. No adverse effects or intolerances to treatment occurred. CONCLUSIONS: Compared with placebo, BLF supplementation alone or in combination with LGG reduces the incidence of NEC of any stage in VLBW neonate

Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants : a randomized controlled trial

Lactoferrin is a mammalian milk glycoprotein involved in innate immunity. Recent data show that bovine lactoferrin (bLF) prevents late-onset sepsis in preterm very low birth weight (VLBW) neonates. METHODS: This is a secondary analysis of data from a multicenter randomized controlled trial where preterm VLBW neonates randomly received bLF (100 mg/day; group A1), bLF + Lactobacillus rhamnosus GG (10(6) colony-forming units per day; group A2), or placebo (group B) for 6 weeks. Here we analyze the incidence rates of fungal colonization, invasive fungal infection (IFI), and rate of progression from colonization to infection in all groups. RESULTS: This study included 472 neonates whose clinical, nutritional, and demographical characteristics were similar. Overall, the incidence of fungal colonization was comparable (17.6%, 16.6%, and 18.5% in A1, A2, and B, respectively; P = .89 [A1] and .77 [A2]). In contrast, IFIs were significantly decreased in A1 and A2 (0.7% and 2.0%, respectively) compared with B (7.7%; P = .002 [A1] and .02 [A2]), and this was significantly true both in <1000 g (0.9% [A1] and 5.6% [A2], vs 15.0%) and in 1001 to 1500 g infants (0% and 0% vs 3.7%). The progression rate colonization-infection was significantly lower in the bLF groups: 3.7% (A1) and 12% (A2), vs 41.9%; P < .001 (A1) and P = .02 (A2). No IFI-attributable deaths occurred in the treatment groups, versus 2 in placebo. No adverse effects or intolerances occurred. CONCLUSIONS: Prophylactic oral administration of bLF reduces the incidence of IFI in preterm VLBW neonates. No effect is seen on colonization. The protective effect on IFI is likely due to limitation of ability of fungal colonies to progress toward invasion and systemic disease in colonized infants

SuperB: A High-Luminosity Asymmetric e+e- Super Flavour Factory. Conceptual Design Report.

May 18, 2007. 480pp., Available on the World Wide Web, with figures in full color, at http://www.pi.infn.it/SuperB/?q=CDRThe physics objectives of SuperB, an asymmetric electron-positron collider with a luminosity above 10^36/cm^2/s are described, together with the conceptual design of a novel low emittance design that achieves this performance with wallplug power comparable to that of the current B Factories, and an upgraded detector capable of doing the physics in the SuperB environment

SuperB: A High-Luminosity Asymmetric e+e- Super Flavour Factory. Conceptual Design Report.

May 18, 2007. 480pp., Available on the World Wide Web, with figures in full color, at http://www.pi.infn.it/SuperB/?q=CDRThe physics objectives of SuperB, an asymmetric electron-positron collider with a luminosity above 10^36/cm^2/s are described, together with the conceptual design of a novel low emittance design that achieves this performance with wallplug power comparable to that of the current B Factories, and an upgraded detector capable of doing the physics in the SuperB environment

SuperB: A High-Luminosity Asymmetric e+ e- Super Flavor Factory. Conceptual Design Report.

The physics objectives of SuperB, an asymmetric electron-positron collider with a luminosity above 10^36/cm^2/s are described, together with the conceptual design of a novel low emittance design that achieves this performance with wallplug power comparable to that of the current B Factories, and an upgraded detector capable of doing the physics in the SuperB environment