Comparison 1. Arginine versus placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 NEC any stage	3	285	Risk Ratio (M‐H, Fixed, 95% CI)	0.38 [0.23, 0.64]
2 Stage 1 NEC	3	285	Risk Ratio (M‐H, Fixed, 95% CI)	0.37 [0.15, 0.90]
3 Stage 2 NEC	3	285	Risk Ratio (M‐H, Fixed, 95% CI)	0.51 [0.25, 1.06]
4 Stage 3 NEC	3	285	Risk Ratio (M‐H, Fixed, 95% CI)	0.13 [0.02, 1.03]
5 Mortality	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
5.1 Mortality due to any cause	3	285	Risk Ratio (M‐H, Fixed, 95% CI)	0.77 [0.41, 1.45]
5.2 Mortality due to NEC	3	285	Risk Ratio (M‐H, Fixed, 95% CI)	0.18 [0.03, 1.00]
6 Plasma arginine concentrations (μmol/L)	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
6.1 Baseline	2	202	Mean Difference (IV, Fixed, 95% CI)	‐10.0 [‐23.85, 3.85]
6.2 At day 14	2	202	Mean Difference (IV, Fixed, 95% CI)	70.0 [50.40, 89.60]
6.3 At day 28	1	152	Mean Difference (IV, Fixed, 95% CI)	79.0 [57.09, 100.91]
7 Plasma glutamine concentrations (μmol/L)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
7.1 Baseline	1	152	Mean Difference (IV, Fixed, 95% CI)	‐40.00 [‐91.88, 7.88]
7.2 At day 14	1	152	Mean Difference (IV, Fixed, 95% CI)	27.0 [‐22.88, 76.88]
7.3 At day 28	1	152	Mean Difference (IV, Fixed, 95% CI)	82.0 [17.72, 146.28]
8 Side effects	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
8.1 Hypotension	3	285	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.41, 2.59]
8.2 Alteration in glucose homeostasis	3	285	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Cerebral palsy	1	135	Risk Ratio (M‐H, Fixed, 95% CI)	0.88 [0.21, 3.80]
10 Cognitive delay (cognitive index < 70)	1	135	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.14, 4.55]
11 Visual impairment	1	135	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
12 Deafness	1	135	Risk Ratio (M‐H, Fixed, 95% CI)	3.52 [0.15, 84.98]
13 Major neurodevelopmental disability	1	132	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.23, 1.83]
14 PDA (%)	3	285	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.75, 1.24]
15 IVH grade III or IV	2	235	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.43, 1.68]
16 Faecal calprotectin (μg/g)	1	249	Mean Difference (IV, Random, 95% CI)	20.13 [‐41.66, 81.92]
16.1 At day 3	1	83	Mean Difference (IV, Random, 95% CI)	32.10 [‐114.31, 178.51]
16.2 At day 14	1	83	Mean Difference (IV, Random, 95% CI)	55.80 [‐46.13, 157.73]
16.3 At day 28	1	83	Mean Difference (IV, Random, 95% CI)	‐13.40 [‐105.05, 78.25]
17 Median age at NEC diagnosis			Other data	No numeric data