Table 1 Characteristics of included studies

Amin et al.[30]

Randomized, double-blind, placebo-controlled, intention to treat basis

Total 254 infants eligible for the study

Study group: 1.5 mmol/kg per day L-arginine added to TPN. Once enteral feeds >40% TFI, L-arginine supplemented enterally

Primary outcome – NEC, all stages

Adequate

Total 152 enrolled

Masking of allocation – Yes

Total 150 infants followed up, 1 died before commencing the study supplement, 1 was removed for IVH Grade ≥2

Control group: normal saline (same volume)

Masking of intervention – Yes

Masking of outcome assessment – Yes

Excluded patients with severe congenital anomalies, congenital non-bacterial infection, evidence of IVH Grade ≥2 on cranial ultrasound by day 3 of life, conjugated hyperbilirubinemia, evidence of an inborn error of metabolism, exchange transfusion during the study period, or with pre-existing kidney failure

Completeness of follow-up – Yes

Inclusion criteria – birth weight ≤1250 g and gestational age ≤32 weeks

Polycarpou et al. [31]

Randomized, double-blind, placebo controlled

Total 171 infants eligible for the study

Study group: 1.5 mmol/kg per day liquid BID with NG feeds, from day 3–28 after birth.

Primary outcome – NEC

Adequate

Masking of allocation – Yes

Total 83 enrolled

Control group: 5% glucose in equivalent volume

Masking of intervention – Yes

Total 83 infants followed up

Masking of outcome assessment – Yes

Excluded patients with severe congenital anomalies or inborn errors of metabolism.

Completeness of follow-up – Yes

Did not exclude patients with IVH Grade Stage ≥ 2

Inclusion criteria – birth weight ≤ 1500 g and gestational age ≤ 34 weeks