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Leucine Improves Growth of Preterm Pigs

Preterm birth is the leading cause of infant death and childhood intellectual and developmental disabilities. Although neonatal growth is a determinant of neurological and long‐term outcomes of preterm infants, and particularly those born small for gestational age (SGA), extrauterine growth retardation (EUGR) caused by inadequate nutrition is common. Moreover, there are complications associated with long‐term reliance on parenteral nutrition. A goal of preterm nutrition support is to provide enteral nutrition that will achieve growth rates that are similar to the rapid in utero growth between 22 and 40 weeks of gestation and allow for normal neurological development and improved outcomes. Currently, preterm infants are provided additional protein compared to term infants to enhance protein accretion, which can increase nitrogenous wastes. We speculated the increased protein synthesis of neonatal term pigs in response to leucine would apply to preterm pigs. We evaluated growth and intestinal responses of preterm pigs relevant to 32 week preterm infants that were fed for 6 to 7 days (120 ml/kg‐d) a lactose based formula that does not cause necrotizing enterocolitis with protein levels of 50 g/L (similar to sow milk) and 100 g/L, with either leucine (10 g/L) added as a growth promoter or alanine (6.8 g/L) as the control. Growth rate was influenced by birth weight (P<0.05) and was unexpectedly higher for pigs fed the two low protein formulas (3.30 ± 0.14 %/d vs 2.74 + 0.27; P=0.02). This may be related to a protein sparing effect by the MCT oil added to the low protein formula to keep the formulas isocaloric. The growth response to leucine compared with alanine was more pronounced for the low compared with the high protein formula (14% vs 8%), and particularly for SGA pigs born at <700 g (P<0.01 for comparison with pigs born >1000 g). The low protein formulas resulted in lower blood urea nitrogen values (2 vs 36 mg/dL; P<0.05), smaller stomachs and small intestines (g/kg), and reduced forskolin stimulated chloride secretion, but glucose uptakes were similar to pigs fed the high protein formula. Pigs fed the formulas with supplemental leucine had higher total small intestinal activity for lactase, but not for maltase and maltodextrinase. These findings indicate leucine is an effective growth promoter for preterm pigs as previously reported for term pigs, particularly for pigs considered as SGA, and more so when added to a formula with a protein content comparable to sow milk, suggesting growth can be improved without the need to provide excessive protein. These findings further support the use of the preterm pig as a translational model for evaluating growth and developmental responses to nutrition support strategies and growth promoters.