Abstract
Growth after preterm birth is an important determinant of long-term outcomes. Yet, many preterm infants suffer ex utero growth retardation. We evaluated effects of leucine and the metabolite, β-hydroxy β-methylbutyrate (HMB) on growth of preterm pigs, a previously-validated translational model for preterm infants. After 48 h of parenteral nutrition preterm pigs were fed for 6 to 7 days isocaloric formulas with different levels of protein (50 or 100 g/L) with leucine (10 g/L, 76 mM) or HMB (at 1.1 g/L, 4 mM) added to stimulate protein synthesis or with alanine (6.8 g/L; 76 mM) as the control. Rates of growth of pigs fed the low protein formula with alanine (3.4 ± 0.2% gain per day) or leucine (3.7 ± 0.2) exceeded that of pigs fed the high protein formula (2.8 ± 0.2, p = 0.02 for comparison with both low protein formulas; p = 0.01 compared with low protein + leucine). Supplementing the high protein formula with leucine or HMB did not increase growth relative to alanine (2.72 ± 0.20, 2.74 ± 0.27, and 2.52 ± 0.20, respectively). Small pigs (<700 g birth weight) grew slower during parenteral nutrition and had a more pronounced response to leucine. Females fed the high protein formulas grew faster than males, and particularly for small pigs (p < 0.05). Blood urea nitrogen values were lower for pigs fed the low versus the high protein formulas (p < 0.05). Leucine and HMB improved growth of preterm pigs fed low, but not high protein formulas, even after controlling for birth weight and sex, which independently correlated with growth rates. They offer an option to improve growth without increasing the amino acid load, with its attendant metabolic disadvantages.
Highlights
Preterm birth is the leading cause of infant death and developmental disabilities [1] and the risk of poor outcomes is increased further with extrauterine growth retardation (EUGR) [2,3]
Leucine and hydroxy β-methylbutyrate (HMB) improved growth of preterm pigs fed low, but not high protein formulas, even after controlling for birth weight and sex, which independently correlated with growth rates
The immediate change from parenteral nutrition (PN) to only enteral nutrition (EN) experienced by the pigs, contrasts with the gradual transition used for preterm infants
Summary
Preterm birth is the leading cause of infant death and developmental disabilities [1] and the risk of poor outcomes is increased further with extrauterine growth retardation (EUGR) [2,3]. A goal of preterm nutrition support is to match the rapid growth of fetuses between 22 and 40 weeks of gestation and protein accretion of 2 to 2.5 g/kg-day [4,5,6] and thereby improve outcomes [7]. Preterm infants are provided 2.5 to 3.5 g of amino acids/kg-day while reliant on parenteral nutrition (PN) [8] and 3 to 4 g of dietary protein/kg-day when fed formulas [9]. The high amounts of protein can compromise growth of preterm infants [10,11], increase the risk of obesity later in life [12], and overload the immature abilities of the hepatic and renal systems to handle excessive nitrogenous wastes, leading to acidosis, elevated blood urea nitrogen (BUN), Nutrients 2018, 10, 636; doi:10.3390/nu10050636 www.mdpi.com/journal/nutrients. Achieving acceptable growth without providing excessive amino acid/protein is desirable
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