(a)

Premature or ELBW infants on parenteral nutrition	n	Combined with other immunonutrients or inducers	Dose	Route	Duration	Mortality	Hospital- acquired infections	Length of stay	Organ function/Morbidity	Inflammation
Extremely low birth weight infants [76]	1433	No	Isonitrogenous study amino acid solution with 20% glutamine	Early parenteral nutrition	120 days	NS	NS	NS	Increased plasma Glutamine concentrations but also more days of PN support. No differences of late onset sepsis, NEC, day to first and full enteral feeds, feeding intolerance, or growth	—
Premature infants ≤32 weeks gestation with a birth weight from 694 to 1590 g [77]	20	No	0.6 g/kg/day	Early parenteral nutrition with amino acid intake 3.0 g/kg/day for at least 3 days	Tracer isotope studies at 6 to 7 days old	—	—	—	Supplemental glutamine was associated with a lower rate of appearance of glutamine, phenylalanine, and leucine C. No difference in leucine N and urea turnover	No significant difference in plasma cortisol and C-reactive protein levels
Ill preterm neonates of <1000 g birth-weight [78]	35	No	16% of the total amino acids (amino acids 1–3.0 g/kg/day)	Early parenteral nutrition	For 7 days or more	—	NS	NS	No significant differences between the groups in blood urea nitrogen, plasma ammonia, plasma glutamine, or glutamate	No significant differences in white cell count, differential white cell count, lactate, pyruvate
Infants after major digestive-tract surgery [79]	41	No	0.4 g/kg/day	Early parenteral nutrition	1–4 weeks	NS	NS	NS	—	—
VLBW age < 3 d, birth wt: 820–1650 g; GA: 28–30 wk [80]	13	No	0.5 g/kg/day	Exclusive parenteral nutrition	Day 4 of life for 24 hours	—	—	—	Decreased rates of Leu release from protein breakdown and Leu oxidation, decreased rates of nonoxidative Leu disposal (an index of whole-body protein synthesis), safe	—
Premature infants [81]	53	No	Isonitrogenous study amino acid solution with 20% glutamine	Early parenteral nutrition	14 days	NS	Lower	Shorter	Fewer days on PN, regained birth weight sooner	—
VLBW premature neonates age < 4 d receiving PN for <3 d; birth wt: 530–1250 g; GA < 32 wk [82]	44	No	15–25% of amino acid mix	Early parenteral nutrition	14 ± 6 days	—	—	NS	Birth wt < 800 g subgroup fewer d on PN, fewer d to full feeds, fewer d on ventilator, safe	Higher lymphocyte count
Infants with birth weights of 401–1000 g [83]	141	No	Isonitrogenous amino acid solution with 20% of the total amino acids as glutamine	Parenteral glutamine supplementation on plasma amino acid concentrations	10 days	—	—	—	No significant difference between the 2 groups in the relative change in plasma glutamate concentration but significant decreases in plasma phenylalanine and tyrosine between the baseline and PN samples
VLBW Infants [84]	30	No	0.3 g/kg/day	Early parenteral nutrition	For ≥7 days	NS	NS	NS	No differences in time to full EN, episodes of gastric residual, total duration of PN, weight gain; hepatic function improved	—
Surgical infants less than 3 months old who required parenteral nutrition [85]	174	No	0.6 g/kg/day or isonitrogenous isocaloric parenteral nutrition (control group)	Early parenteral nutrition	Until full enteral feeding	NS	NS	—	No difference in time to full enteral feeding or time to first enteral feeding	—