Nutrient Metabolism Preterm Birth Affects the Intestinal Response to Parenteral and Enteral Nutrition in Newborn Pigs 1,2 Per T. Sangild,* 3 Yvette M. Petersen,* Mette Schmidt,* Jan Elnif,* Thomas K. Petersen, † Randal K. Buddington,** Gorm Greisen, ‡ Kim F. Michaelsen †† and Douglas G. Burrin ‡‡ *Divisions of Nutrition and Reproduction, Royal Veterinary and Agricultural University, Frederiksberg DK-1870, Denmark; † Leo Pharmaceutical Products, Department of Pharmacology, Ballerup DK-2750, Denmark; **Department of Biological Sciences and the College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762; ‡ Neonatology Clinic, State University Hospital (Rigshospitalet), Copenhagen DK-2100, Denmark; †† Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Frederiksberg, Denmark; and the ‡‡ U.S. Department of Agriculture/Agricultural Research Service Children’s Nutrition Research Center, Houston, TX 77030 ABSTRACT Maturation of gastrointestinal (GI) function in neonates is stimulated by enteral nutrition, whereas parenteral nutrition induces GI atrophy and malfunction. We investigated whether preterm birth alters the GI responses to parenteral and enteral nutrition. Pigs were delivered either preterm (107 d gestation) or at term (115 d gestation) and fed total parenteral nutrition (TPN) or enteral sow’s milk (ENT) for 6 d after birth. Immaturity of the preterm pigs was documented by reduced blood pH, oxygen saturation and neutrophil granulocyte function, impaired intestinal immunoglobulin G uptake from colostrum, and altered relative weights of visceral organs (small intestine, liver, spleen, pancreas, and adrenals). For both ages at delivery, increases occurred in pancreatic weight (30 –75%) and amylase activity (0.5- to 13-fold) after birth, but much more in ENT than in TPN pigs (P  0.05). Six days of TPN feeding was associated with reduced intestinal weight for both delivery groups (60% of values in ENT, P  0.001), but only in term TPN pigs was the weight lower than at birth (-20%, P  0.05). Likewise, it was only in term TPN pigs that intestinal maltase activity increased, compared with ENT, and the absorption of glucose and proline decreased. Only in preterm pigs did TPN feeding increase lactase activity (+50% compared with ENT, P  0.05). For both delivery ages, the mRNA of lactase-phloridzin hydrolase and sodium-coupled glucose transporter 1 were increased in TPN, compared with ENT. In conclusion, the trophic effect of enteral vs. parenteral nutrition on the GI tract is also present after preterm birth, but the postnatal maturation of many GI functions is modified, compared with term birth. The effects of nutritional regimen on the maturation of the gut epithelium in neonates depend on gestational age at birth. J. Nutr. 132: 2673–2681, 2002. KEY WORDS: ● ontogeny ● birth ● nutrient absorption ● brush-border enzymes ● development In many species, including humans, the gastrointestinal tract (GIT) 4 undergoes marked structural and functional mat- uration in the periods immediately before and after birth (1– 8). Correspondingly, preterm birth is associated with a variable degree of GIT immaturity and intolerance to oral feeding. Preterm neonates, thus, may require a period of total parenteral nutrition (TPN) before enteral nutrition is admin- istered (9 –11). The intensity of care is inversely related to the length of gestation and degree of organ immaturity at birth. The onset of enteral nutrition at birth is a key signal for the marked maturation of the GIT in term newborn animals (4,7,8,12). Conversely, administering TPN to neonates in- duces intestinal atrophy and may reduce the digestive and absorptive capacity (13–16). It is not known whether maturity at birth affects the responsiveness of the intestine to nutrition. In guinea pigs, intestinal growth after 24 h of enteral feeding is greater in prematurely delivered animals (93% gestation) than in those delivered at term (17). These results suggest that the intestinal trophic response to enteral feeding may be influenced by gestational age at birth. One of the limitations in our understanding of prematurity and intestinal function is the lack of an appropriate animal model. Whereas primates and guinea pigs are viable from 70% gestation, species such as pigs, dogs and rats are not 1 Supported by the Danish Agricultural and Veterinary Research Council, Programme 9702803. 2 A preliminary account of the data has been published: Sangild, Petersen, Y. M., Elnif, J., Schmidt, M., Buddington, R. K. & Burrin, D. G. (2000) Prema- ture and term newborn pigs differ in their intestinal response to parenteral and enteral nutrition. Gastroenterology 118: A76. 3 To whom correspondence should be addressed. E-mail: psa@kvl.dk. 4 Abbreviations used: ApA, aminopeptidase A; ApN, aminopeptidase N; DPP IV, dipeptidyl peptidase IV; ENT, enteral nutrition; GI, gastrointestinal; GIT, gas- trointestinal tract; IgG, immunoglobulin G; LPH, lactase-phloridzin hydrolase; LS, least square; O 2 ct, oxygen content; O 2 sat, oxygen saturation; pCO 2 , partial carbon dioxide pressure; PMN, polymorphonuclear neutrophil granulocytes; pO 2 ; partial oxygen pressure; RT-PCR, reverse transcription polymerase chain reac- tion; SGLT-1, sodium-coupled glucose transporter 1; TPN, total parenteral nutri- tion. 0022-3166/02 $3.00 © 2002 American Society for Nutritional Sciences. Manuscript received 20 March 2002. Initial review completed 9 April 2002. Revision accepted 18 June 2002. 2673 Downloaded from https://academic.oup.com/jn/article/132/9/2673/4687862 by guest on 12 February 2023