Kuusela 1997.

Methods	Randomised controlled trial in Finland.
Participants	Inclusion criteria: infants starting mechanical ventilation during the first 2 hours of life in the neonatal ICU. Exclusion criteria: infants who did not undergo mechanical ventilation during the first 2 hours of life in the neonatal ICU. Further information regarding participants: 53 mechanically ventilated newborn infants with data for 48 reported: mean gestational age 32 weeks (range 24 to 41 weeks). Ranitidine group mean and 95% CI (31 (29 to 33)); control group mean and 95% CI (32 (29 to 32)). Birth weight in grams (mean (95% CI)): ranitidine group 1678 (1241 to 2114); control group 1972 (1534 to 2412). Study period: 10 months.
Interventions	Intervention (n = 23): ranitidine: 5 mg/kg/day intravenous, divided into 3 doses throughout 4 days Control (n = 25): no prophylaxis (no placebo was available).
Outcomes	Mucosal lesions detected on endoscopy; histologic lesions and bacterial evaluation of gastric mucosal biopsies; death and suspected or proven late onset bacteraemia.
Notes	Conflicts of interest: none reported. Supported, in part, by a grant from the Finnish Foundation of Pediatric Research. Authors did not believe there were any adverse reactions attributable to the intervention.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Reported: "mechanically ventilated newborns at the neonatal ICU were randomised into either the treatment group (prophylactic intravenous ranitidine [5 mg/kg body weight/day] divided into three doses throughout 4 days) or the control group (no prophylaxis)." "The first randomisation block included 20 envelopes in random order for both groups, followed by two randomisation blocks of ten envelopes for the more preterm babies. Babies closer to term were randomised in one block with 20 envelopes." Method of random sequence generation not reported.
Allocation concealment (selection bias)	Unclear risk	The methods of allocation concealment were not specified. It is not reported if envelopes were sealed and opaque.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Reported: "Only the sequence number of the patient was written in the patient records by the nurse responsible for medication. Thus, the attending physicians, the endoscopist, and the pathologist remained blinded as to the treatment group." "The clinical data on the patients up to the age of 4 weeks were collected from patients’ records after the children had been discharged but before the opening of the randomisation code." There was no placebo ‒ no treatment was used in the control group so adequacy of clinical blinding is unclear.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Reported: "the attending physicians, the endoscopist, and the pathologist remained blinded as to the treatment group."
Incomplete outcome data (attrition bias) All outcomes	Low risk	5 neonates (9% ‒ 3 treatment group; 2 control group) dropped out of the study after the randomisation and before gastroscopic evaluation. These patients were not included in the study because of early death (2 patients at gestational age of < 33 weeks and 1 patient at gestational age of ≥ 33 weeks) and because of oesophageal atresia (1 patient in both groups).
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement of ‘low risk’ or ‘high risk’ ‒ protocol not available.
Other bias	Low risk	No other bias noted. Infant characteristics were similar between intervention and control groups.