Intrauterine growth restriction (IUGR) and preterm birth are leading causes of neonatal morbidity. We tested the hypothesis that IUGR predisposes to gut maladaption and necrotizing enterocolitis (NEC) using preterm pigs as models for preterm infants. First, full term normal birth weight (NW) and IUGR ( approximately 65% of NW) pigs were compared. IUGR reduced intestinal weight per length, proportion mucosa, villous area, and sucrase activity at 2 d after birth (p<0.05), but did not change relative organ weights. Next, groups of preterm pigs were fed formula or colostrum, starting at birth or after 3 d of total parenteral nutrition (TPN). Neonatal mortality (not related to NEC) was increased in IUGR vs. NW preterm pigs (28 vs. 10%, p<0.01). NEC incidence was similar between IUGR and NW but higher after formula than colostrum feeding (46 vs. 12%, p<0.01), and higher after TPN than without TPN (61 vs. 34% for formula pigs, p<0.01). Following feeding, relative intestinal mass and length was higher in IUGR vs. NW pigs (+25-80%, p<0.05) while brush border enzyme activities were similar. An enhanced gut trophic response to enteral feeding may help to improve postnatal intestinal adaptation and NEC resistance in preterm IUGR newborns