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Title: Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs

Author
item SHEN, RENE - University Of Copenhagen
item THYMANN, THOMAS - University Of Copenhagen
item OSTERGAARD, METTE - University Of Copenhagen
item STOY, ANN - Technical University Of Denmark
item KRYCH, LUKASZ - University Of Copenhagen
item NIELSEN, DENNIS - University Of Copenhagen
item LAURIDSEN, CHARLOTTE - Aarhus University
item HARTMANN, BOLETTE - University Of Copenhagen
item HOLST, JENS - University Of Copenhagen
item Burrin, Douglas - Doug
item SANGLID, PER - University Of Copenhagen

Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/30/2015
Publication Date: 7/2/2015
Citation: Shen, R.L., Thymann, T., Ostergaard, M.V., Stoy, A.C., Krych, L., Nielsen, D.S., Lauridsen, C., Hartmann, B., Holst, J.J., Burrin, D.G., Sanglid, P.T. 2015. Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs. American Journal of Physiology - Gastrointestinal and Liver Physiology. 309(5):G310-G323.

Interpretive Summary: Premature infants are at an increased risk for an intestinal disease called necrotizing enterocolitis (NEC). Studies in these infants show that oral feeding of formula by mouth or a tube into the stomach can trigger NEC, but mother's breast milk protects against this disease. Because of this concern about NEC, premature infants that are fed commercial formulas are gradually fed small amounts over a period of days immediately after birth, a technique called minimal enteral nutrition. In addition, natural alternatives to processed formulas are being considered such as cow colostrum, the milk produced in the first day after birth of calves. The aim of this study was to test whether giving either formula or bovine colostrum as minimal enteral nutrition prevents or reduces NEC in premature piglets. The results suggest that formula even when given as minimal enteral nutrition can induce mild NEC and that feeding cow colostrum instead can effectively reduce the NEC incidence. These studies provide good proof in a premature pig that cow colostrum may be an effective alternative milk that can be fed to tiny infants to reduce the risk of contracting this devastating disease.

Technical Abstract: It is unclear when and how to start enteral feeding for preterm infants when mother's milk is not available. We hypothesized that early and slow advancement of either formula or bovine colostrum stimulates gut maturation and prevents necrotizing enterocolitis (NEC) in preterm pigs, used as models for preterm infants. Pigs were given either total parenteral nutrition (TPN, n = 14), slowly advancing volumes (16-64 mL / kg(-1) / d(-1)) of preterm infant formula (IF, n = 15) or bovine colostrum (BC, n = 13), both given as adjunct to parenteral nutrition. On day five, both enteral diets increased intestinal mass (27 +/- 1 vs. 22 +/- 1 g/kg) and glucagon-like peptide 2 release, relative to TPN (P < 0.05). The incidence of NEC lesions was higher in IF than BC and TPN pigs (60 vs. 0 and 15%, respectively, P < 0.05). Only the IF pigs showed reduced gastric emptying and gastric inhibitory polypeptide release, and increased tissue proinflammatory cytokine levels (IL-1ß and IL-8, P < 0.05) and expression of immune-related genes (AOAH, LBP, CXCL10, TLR2), relative to TPN. The IF pigs also showed reduced intestinal villus/crypt-ratio, lactose digestion, and some plasma amino acids (Arg, Cit, Gln, Tyr, Val), and higher intestinal permeability, compared with BC pigs (all P < 0.05). Colonic microbiota analyses showed limited differences among groups. Early feeding with formula may induce intestinal dysfunction while bovine colostrum may support gut maturation when mother's milk is absent during the first week after preterm birth. A diet-dependent feeding guideline may be required for newborn preterm infants.