El‐Shimi 2015.

Methods	Three‐arm, comparative, prospective randomised study 1. Masking of randomisation: yes 2. Masking of intervention: unclear; yes according to study authors, but one group received no intervention. Thus it is unclear how this could have been achieved. 3. Completeness of follow‐up: yes 4. Masking of outcome assessment: yes
Participants	75 infants ≤ 34 weeks' gestation at birth were enrolled after parental consent. Arginine group (N = 25): Mean (SD) birth weight was 1450 (260) grams and gestational age was 31.84 (2.3) weeks Glutamine group (N = 25): Mean (SD) birth weight was 1310 (250) grams and gestational age was 30.64 (2.3) weeks Control (no treatment) group (N = 25): Mean (SD) birth weight was 1450 (210) grams and gestational age was 31.86 (1.4) weeks Exclusion criteria: newborns with congenital malformations, chromosomal abnormalities, suspected inborn error of metabolism, sepsis, IVH grade ≥ II, undergoing intestinal surgery or having any contraindication to enteral feeding
Interventions	Arginine group: Infants received L‐arginine (0.75 mmol/kg/d) with the start of enteral feedings, doubled to 1.5 mmol/kg/d (261 mg/kg/d) when 40% of enteral feeding (60 cc/kg) was reached. Arginine was supplemented until 30 days' postnatal age. The dose was administered orally or via nasogastric tube every 12 hours Glutamine group: Infants received glutamine (156 mg/kg/d) with the start of enteral feedings, doubled to 312 mg/kg/d when 40% of enteral feeding (60 cc/kg) was reached. Glutamine was supplemented until 30 days' postnatal age. The dose was divided every 12 hours and was taken orally or via nasogastric tube. Control group: Infants started enteral feeding within first week without arginine or glutamine supplementation
Outcomes	NEC, all stages NEC, stage 2 NEC, stage 3 Mortality due to NEC Mortality due to any cause Arginine concentrations at baseline, at time of NEC diagnosis and at day 14 of life
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Simple randomisation method was based on computer‐generated sequence.
Allocation concealment (selection bias)	Low risk	Allocation was concealed (information provided by study authors).
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Participants, doctors and nurses evaluating outcomes were blinded to intervention allocation according to study authors; however, it is unclear how this may have been achieved when the control group received no intervention (information provided by study authors).
Incomplete outcome data (attrition bias) All outcomes	Low risk	All randomised participants were accounted for in the analysis.
Selective reporting (reporting bias)	Low risk	The registered primary outcome and the reported primary outcome were aligned. No prespecified secondary outcomes were stated.
Other bias	Low risk