(b)

Premature or ELBW infants on enteral nutrition	n	Combined with other immunonutrients or inducers	Dose	Route	Duration	Mortality	Hospital- acquired infections	Length of stay	Organ function/Morbidity	Inflammation
VLBW age < 3 d receiving PN; birth wt: 500–1250 g; GA: 24–32 wk [86]	68	No	0.08 g/kg/d on d3 and reached 0.31 g/kg/d by d13	Glutamine-enriched enteral nutrition (PN n = 35)	Day 3–30 of life	NS	Reduced hospital-acquired sepsis (positive blood culture)	NS	No differences in NEC, wt, length, head circumference, mechanical ventilation, safe	Blunted the rise in HLA-DR+ and CD16/CD56 subsets
Critically ill infants 1–24 mo tolerating EN [87]	9	No	0.3 g/kg/day	Glutamine-enriched enteral nutrition	5 days	NS	NS	NS	Well tolerated and safe	—
VLBW age < 7 d receiving PN; birth wt: 500–1250 g [87]	649	No	0.3 g/kg/day	Within the first 7 d of age, randomly assigned to enteral glutamine supplement (3% glutamine in sterile water) or placebo (sterile water) given at the same time but separate from feedings	7 days–36 weeks post menstrual age	NS	NS	NS	Less gastrointestinal dysfunction, severe neurological sequelae among survivors (grades 3 and 4 intraventricular hemorrhage and paraventricular leukomalacia) in glutamine group. No difference in NEC, retinopathy of prematurity, oxygen use at 36 weeks, or growth,	—
VLBW infants < 48 h after birth receiving PN; birth wt: <1500 g; GA < 32 wk [88]	102	No	Increasing doses from day 3–30 of life to a maximum dose of 0.3 g/kg/day	Glutamine-enriched isonitrogenous enteral nutrition added to breast milk or preterm formula	Day 3–30 of life	NS	Lower incidence of ≥1 serious infections	NS	No difference in feeding tolerance, NEC, or growth, patent ductus arteriosus, mechanical ventilation, supplemental oxygen, retinopathy	—
VLBW < 48 h after birth receiving PN; birth wt: <1500 g; GA < 32 wk [89]	86	No	Increasing doses to ≤0.3 g/kg/day	Enteral preterm formula or breast milk supplemented with Glutamine or isonitrogenous Ala	Day 3–30 of life	NS	NS	—	No difference in prevalence of intestinal microflora (bifidobacteria, lactobacilli, Escheria coli, streptococci, clostridia) at <48 h–d30 of life, by fluorescent in situ hybridization	—
VLBW < 48 h after birth receiving PN; birth wt: <1500 g; GA < 32 wk [90]	90	No	Increasing doses to ≤0.3 g/kg/day	Enteral preterm formula or breast milk supplemented with glutamine or isonitrogenous Ala	Day 3–30 of life	NS	NS	—	No difference in decreased lactulose/mannitol ratio or urinary lactulose or increased urinary mannitol concentrations	—
VLBW infants <48 h after birth receiving PN; birth wt: < 1500 g; GA < 32 wk [91]	63	No	Increasing doses to ≤0.3 g/kg/day	Enteral preterm formula or breast milk supplemented with glutamine or isonitrogenous Ala	Day 3–30 of life	NS	NS	—	—	No differences in Th1 or Th2 cytokine responses at 48 h–d 14 of life following in vitro whole blood cell stimulation

ELBW: extremely low birth weight; VLBW: very low birth weight; Wt: weight; GA: gestational age; AA: amino acid; PN: parenteral nutrition; EN: enteral nutrition; LOS: length of stay; NEC: necrotizing enterocolitis; NB: nitrogen balance; IL: interleukin; NS: nonstatistical difference.