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Title: Enteral feeding induces diet-dependent mucosal dysfunction, bacterial overgrowth and necrotizing enterocolitis in preterm parenterally-fed pigs

Author
item BJORNVAD, C - UNIV. COPENHAGEN, DENMARK
item THYMANN, T - UNIV. COPENHAGEN, DENMARK
item DEUTZ, N - MAASTRICHT UNIV., DENMARK
item Burrin, Douglas - Doug
item JENSEN, S - UNIV. AARHUS, DENMARK
item JENSEN, B - UNIV. AARHUS, DENMARK
item MOLBAK, L - TECHNICAL UNIV. DENMARK
item BOYE, M - AARHUS UNIV., DENMARK
item LARSSON, L - UNIV. COPENHAGEN, DENMARK
item SCHMIDT, M - UNIV. COPENHAGEN, DENMARK
item SANGILD, P - UNIV. COPENHAGEN, DENMARK

Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/1/2008
Publication Date: 11/1/2008
Citation: Bjornvad, C.R., Thymann, T., Deutz, N.E., Burrin, D.G., Jensen, S.K., Jensen, B.B., Molbak, L., Boye, M., Larsson, L., Schmidt, M., Sangild, P.T. 2008. Enteral feeding induces diet-dependent mucosal dysfunction, bacterial overgrowth and necrotizing enterocolitis in preterm parenterally-fed pigs. American Journal of Physiology Gastrointestinal Liver Physiology. 295:1092-1103.

Interpretive Summary: A significant component of the health care costs in the United States is associated with the care of infants born preterm. A major gastrointestinal disease in these infants is necrotizing enterocolitis (NEC), with 500,000 preterm infants born annually with an increased risk of developing NEC. In many instances, preterm infants are fed by intravenous infusions of nutrition, called total parenteral nutrition (TPN), because they cannot consume food by mouth like normal term infants. Studies have shown that TPN can retard normal intestinal development and impair function. The goal of this study was to deteremine whether a period of TPN prior to enteral feeding affects the rate of NEC in preterm piglets. The study examined the presence of NEC in groups of piglets that were born premature and fed either TPN for 3 days prior to enteral feeding or fed enterally from birth. The diets fed to each group were porcine or bovine colostrum or formula. The key finding was that the incidence of NEC was much higher in pigs given TPN prior to enteral feeding compared to those fed enterally immediately at birth. Feeding breast milk, either porcine or bovine, reduced the NEC incidence compared to formula. As with previous studies in piglets, we found that specific bacteria are strongly associated with the severity of NEC, namely Clostridium species. The findings suggest that clinicians should minimize the duration of TPN and reduce the intake of formula to reduce the risk of NEC in preterm infants.

Technical Abstract: Preterm neonates have an immature gut and metabolism and may benefit from a period of total parenteral nutrition (TPN) before enteral food introduction. Conversely, delayed enteral feeding may inhibit gut maturation and sensitize to necrotizing enterocolitis (NEC). Intestinal mass and NEC lesions were first recorded in a large number of caesarean-delivered preterm pigs fed enterally (porcine colostrum, bovine colostrum, or formula for 20-40 h), with or without a postnatal 2- to 3-d period of TPN (n=406). Intestinal mass remained unchanged during TPN but increased following enteral feeding (+55%), approaching the growth response in pigs fed only enterally (+69%, all P<0.05). NEC developed only after enteral feeding, and more often with a previous TPN period for both sow's colostrum (26 vs. 5%) and formula (62 vs. 39%) diets (both P < 0.001, n = 43-170). Detailed studies in 3-d-old TPN pigs fed enterally showed that formula feeding decreased villus height and nutrient digestive capacity, and increased luminal lactic acid and NEC lesions, compared with colostrum (bovine or porcine, P<0.05). Mucosal microbial diversity increased with enteral feeding, and Clostridium perfringens density was related to severity of intestinal damage. Formula-feeding decreased plasma arginine and tissue antioxidants, while tissue nitric oxide synthetase and gut permeability increased, relative to colostrum. In conclusion, enteral feeding is associated with gut dysfunction, microbial imbalance and NEC in preterm pigs, especially in pigs fed formula after TPN. Conversely, colostrum milk diets improve gut maturation and NEC resistance in preterm pigs subjected to a few days of TPN after birth.