Table 1.

Study characteristics of included studies

Study	Year	Methods	Participants	Interventions	Primary outcomes		Other effects of intervention
RCTs					Death	Surgery (including surgery for stricture, perforation, and re-NEC)
Hansen [20]	1980	RCT Randomization from number table Blinded intervention	20 infants Overall mean GA: 35.2 weeks Overall mean BW: 2200 g	IV ampicillin 150 mg/kg/day ev. 6 h + IM gentamicin 7.5 mg/kg/day ev. 8 h Intervention Group: + oral gentamicin through nasogastric tube 15 mg/kg/day ev. 4 h	Intervention: 1/10 Control:2/10	Intervention: 1/10 Control: 4/10	Intestinal perforation Intestinal stricture Peritonitis
Faix [21]	1988	RCT Randomization by sealed envelopes Unclear information about blinding	42 infants Overall mean GA: 29,4 weeks Overall mean BW 1300 g	IV ampicillin (<  7 days old 100 mg/kg/day ev. 12 h. > 7 days old 150 mg/kg/day) ev. 8 h + IV gentamicin (< 34 weeks GA 5.0 mg/kg initially then 2.5 mg/kg/day, > 34 weeks GA and < 7 days of age 5.0 mg/kg/day ev. 12 h, > 34 weeks of GA and > 7 days of age 7.5 mg/kg/d ev. 8 h. Intervention group: + IV clindamycin 20 mg/kg/day ev. 8 h	Intervention: 4/20 Control: 4/22	Intervention: 6/20 Control: 4/22	Bowel necrosis Strictures Time to successful reinstitution of enteral feeds Time to resolution of intestinal pneumatosis
Cohorte studies
Vermeylen [22]	1985	Prospective cohort All children admitted during 1978–84 included	77 infants, (Group 1 included 1978–80 = 22 infants. Group 2 included after 1980 = 55 patients). Overall mean GA: 34 weeks Overall mean BW: 2005 g	IV ampicillin + gentamycin + enteral gentamycin 10–15 mg/kg/day ev. 4 h Intervention group: IV ampicillin + aminoglycoside + IV metronidazole booster 15 mg/kg followed by 7,5–10 mg ev. 12 h.	Intervention: 8/53 Control:7/22	Intervention: 17/24 Control: 4/22	Length of hospitalization
Scheifele [10]	1987	Prospective cohort All children admitted during August 1982–May 1985 included	90 infants (1982–83 = 46 infants included, from 1984 to 85 = 44 included infants) Overall mean BW: 1904 g GA?	1982–83: IV ampicillin 100 mg/kg/day + IV gentamicin 5–7.5 mg/kg/day. If age < 7d ev. 12 h, other ev. 8 h. 1984–85 Intervention group: IV cefotaxime 150 mg/kg/day + IV vancomycin 30–35 mg/kg/day. If age < 7d ev. 12 h, other ev. 8 h.	Intervention: 0/44 Control: 5/46	Intervention: 13/44 Control: 15/46	Peritonitis Intestinal perforation Thrombocytopenia Recurrent NEC Intestinal strictures
Luo [23]	2015	Retrospective cohort Infants treated from Jan 2008 to March 2015. Controls were chosen using PS-matching	146 infants (73 intervention group) Overall mean GA 38.86 Overall mean BW 2909 g	All infants received a combination of broad-spectrum antibiotics such as: semisynthetic penicillin, cephalosporin, carbapenems, vanco-mycin. Intervention: IV metronidazole 15 mg/kg/day	Intervention: 9/73 Control:7/73	Intervention: 11/73 Control: 6/73	sepsis blood transfusion Need for nasogastric suction

All included infants had radiological evidence of necrotizing enterocolitis (NEC). Abbreviations: RCT Randomized controlled trial, IM Intramuscular. IV Intravenous. PS Propensity score, ev. Every