Availability of Donor Human Milk Decreases the Incidence of Necrotizing Enterocolitis in VLBW Infants.

BACKGROUND: Human milk feeding is associated with decreased risk of necrotizing enterocolitis (NEC). PURPOSE: To determine whether a quality improvement project in New Jersey neonatal intensive care units (NICUs) to promote human milk (HM) feedings would be associated with a decrease in NEC. METHODS: Fourteen New Jersey NICUs engaged in efforts to reduce infection and promote HM feeding in very low birth-weight (VLBW) infants. Donor human milk (DHM) availability and NEC rates were assessed. RESULTS: From 2009 to 2016, NICUs with DHM increased from 0 to 7. VLBW infants discharged on any HM increased from 35% in 2007 before the formation of the New Jersey NICU Collaborative to more than 55% in 2016. Time to first oropharyngeal colostrum decreased from 37 to 30 hours from 2014 to 2016. HM at first feeding increased from 71% in 2013 to 82% in 2016. There was an increase in the percentage of feeds that were HM over the first 7 days of feeding. Analyses of data from 9400 VLBW infants born between 2009 and 2016 showed that the incidence of NEC when DHM was not available was 5.1% (367/7182) whereas the incidence when DHM was available (64/2218) was significantly lower (2.9%; P < .0001). IMPLICATIONS FOR PRACTICE: These findings show advantages of feeding HM and effectiveness of forming an NICU collaborative for improving care for preterm infants. IMPLICATIONS FOR RESEARCH: New research projects should measure the quantity of HM consumed daily during the entire NICU stay and assess the timing and amount of HM consumption in relationship to incidence of NEC and infection in neonates.

Targeting tissue factor for immunotherapy of choroidal neovascularization by intravitreal delivery of factor VII-Fc chimeric antibody.

PURPOSE: ICON is a fusion protein composed of factor VII, the natural ligand for tissue factor, conjugated to the Fc domain of a human IgG1 immunoglobulin. It binds to the tissue factor expressed on neovascular endothelia and initiates a cytolytic immune attack that destroys the neovascular tissue. We previously showed that mouse factor VII-Fc chimeric antibody (mICON) dramatically decreases the frequency of choroidal neovascularization in a laser-induced choroidal neovascularization model in mice. Herein, we determined the safety and efficacy of mICON in destroying subretinal choroidal neovascularization in pig eyes. METHODS: mICON (150-1200 microg) was administered into the midvitreous cavity of the pig eye either before (on Day 0) or after (on Day 10) induction of choroidal neovascularization with laser photocoagulation. On Day 14, the incidence of choroidal neovascularization was determined using confocal microscopy. We also determined the binding specificity (% binding to choroidal neovascularization/% binding to non-choroidal neovascularization areas) of mICON to tissue factor expressed on endothelial cells of laser-induced choroidal neovascularization. RESULTS: We observed that mICON selectively destroyed choroidal neovascularization in a dose-dependent manner (r = -0.93; EDB50B = 571.3 microg). Obliteration of the choroidal neovascular complex was more prominent at doses > 300 microg (p < 0.05). No systemic or local complications (including retinal tear/detachment, inflammation, infection, cataract, or glaucoma) were observed. Binding specificities of hICON (2.2 +/- 0.2) and mICON (3.4 +/- 0.4) were significantly higher than that of anti-von Willebrand antibody (0.1 +/- 0.01, p < 0.001). CONCLUSIONS: Both hICON and mICON bound to the neovascular endothelia of choroidal neovascularization with greater specificity than anti-von Willebrand antibody. Furthermore, mICON can selectively obliterate already established choroidal neovascularization, which suggests that it may be useful for immunotherapy in patients with exudative (wet) macular degeneration.