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Title: Human milk fortification with bovine colostrum is superior to formula-based fortifier to prevent gut dysfunction, necrotizing enterocolitis, and systemic infection in preterm pigs

Author
item SUN, JING - University Of Copenhagen
item LI, YANQI - University Of Giessen
item PAN, XIAOYU - University Of Copenhagen
item NGUYEN, DUC NINH - Baylor College Of Medicine
item BRUNSE, ANDERS - Rigshospitalet - Copenhagen University Hospital
item BOJESEN, ANDERS M. - University Of Copenhagen
item RUDLOFF, SILVIA - University Of Giessen
item MORTENSEN, MARTIN S. - University Of Copenhagen
item Burrin, Douglas - Doug
item SANGILD, PER T. - University Of Copenhagen

Submitted to: Journal of Parenteral and Enteral Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/15/2018
Publication Date: 6/5/2018
Citation: Sun, J., Li, Y., Pan, X., Nguyen, D., Brunse, A., Bojesen, A., Rudloff, S., Mortensen, M., Burrin, D., Sangild, P. 2018. Human milk fortification with bovine colostrum is superior to formula-based fortifier to prevent gut dysfunction, necrotizing enterocolitis, and systemic infection in preterm pigs. Journal of Parenteral and Enteral Nutrition. http://doi.org/10.1002/jpen.1422
DOI: https://doi.org/10.1002/jpen.1422

Interpretive Summary: Many very premature infants experience poor growth during hospitalization and in the months after birth. Thus, it is critical to provide optimal and adequate nutrients for preterm infants to prevent growth failure. Human milk is critical to maintain health of preterm infants, but must be supplemented to meet their high nutrient needs with processed formula-based fortifiers. There have been concerns raised that some human milk fortifiers increase the risk for intestinal disease. The aim of the current study was to compare pasteurized cow colostrum with two commercial human milk fortifier in preterm piglets as a model of human infants. Newborn piglets were fed donor human milk that was fortified with either cow colostrum or two different commercial fortifiers for 5 days after birth. The results confirm a recent report and showed that donor human milk that is fortified with cow colostrum vs. commercial fortifier resulted in less diarrhea and incidence of necrotizing enterocolitis and improved digestive function. The study suggests that cow colostrum may be an effective alternative to fortify human milk that is fed to newborn preterm infants in the early weeks after birth.

Technical Abstract: Fortification of donor human milk (DHM) is required for optimal growth of very preterm infants, but there are concerns of more gut dysfunction and necrotizing enterocolitis (NEC) when using formula-based fortifiers (FFs), especially soon after birth. Intact bovine colostrum (BC) is rich in nutrients and bioactive factors, and protects against NEC in preterm pigs. We hypothesized that fortification of DHM with BC is superior to FFs to prevent gut dysfunction and infections when provided shortly after preterm birth. Two FF products, Enfamil (ENF; intact protein, vegetable oil) and PreNAN+Nutrilon (NAN; extensively hydrolyzed protein, maltodextrin), were compared with BC as fortifier to DHM fed to preterm pigs for 5 days. Relative to the DHM+BC group, DHM+FF groups had higher diarrhea score and lower hexose uptake and lactase activity, and specifically the DHM+NAN group showed higher gut permeability, NEC score, more mucosa-adherent bacteria with altered gut microbiota structure (ie, lower diversity, increased Enterococcus, decreased Staphylococcus abundance). Both DHM+FF groups showed higher expression of intestinal cytokine and inflammation-related genes, more gut-derived bacteria in the bone marrow, lower density of mucin-containing goblet cells, and slightly higher colon lactate, stomach pH and acetate, and blood neutrophilto-lymphocyte levels than the DHM+BC group. Used as a fortifier to DHM, BC is superior to FFs to support gut function, nutrient absorption, and bacterial defense mechanisms in preterm pigs. It is important to optimize the composition of nutrient fortifiers for preterm infants fed human milk.