Arginine, an
amino acid that is nutritionally essential for the fetus and neonate, is crucial for
ammonia detoxification and the synthesis of molecules with enormous importance (including
creatine,
nitric oxide, and
polyamines). A significant nutritional problem in preterm infants is a severe deficiency of
arginine (hypoargininemia), which results in
hyperammonemia, as well as cardiovascular, pulmonary, neurological, and intestinal dysfunction.
Arginine deficiency may contribute to the high rate of infant morbidity and mortality associated with
premature births. Although hypoargininemia in preterm infants has been recognized for more than 30 years, it continues to occur in neonatal intensive care units in the United States and worldwide. On the basis of recent findings, we propose that intestinal
citrulline and
arginine synthesis (the major endogenous source of
arginine) is limited in preterm neonates owing to the limited expression of the genes for key
enzymes (e.g.,
pyrroline-5-carboxylate synthase,
argininosuccinate synthase and
lyase), thereby contributing to hypoargininemia. Because
premature births in humans occur before the normal perinatal surge of
cortisol (an inducer of the expression of key
arginine-synthetic
enzymes), its administration may be a useful tool to advance the maturation of intestinal
arginine synthesis in preterm neonates. Additional benefits of
cortisol treatment may include the following: 1) allowing early introduction of
enteral feeding to preterm infants, which is critical for intestinal synthesis of
citrulline,
arginine, and
polyamines as well as for intestinal motility, integrity, and growth; and 2) shortening the expensive stay of preterm infants in hospitals as a result of accelerated organ maturation and the restoration of full
enteral feeding. Further studies of fetal and neonatal
arginine metabolism will continue to advance our understanding of the mechanisms responsible for the survival and growth of preterm infants. This new knowledge will be beneficial for designing the next generation of enteral and parenteral
amino acid solutions to optimize nutrition and health in this compromised population.