Comparison 6. High‐dose (oral or IV) versus standard‐dose ibuprofen (oral or IV).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to close a patent ductus arteriosus after 3 doses of ibuprofen	3	190	Risk Ratio (M‐H, Fixed, 95% CI)	0.37 [0.22, 0.61]
2 Reopening after second course of ibuprofen	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.39, 10.22]
3 Need for surgical closure	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.15, 6.71]
4 Mortality during hospital stay	2	155	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.58, 1.79]
5 Urine output on day 3 of treatment (mL/kg/hour)	2	130	Mean Difference (IV, Fixed, 95% CI)	0.21 [‐0.43, 0.85]
6 Oliguria (< 1 mL/kg/hour during 24 hours)	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.5 [0.27, 8.43]
7 Intraventricular haemorrhage (any grade)	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.21, 2.16]
8 Intraventricular haemorrhage (grades III and IV)	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.10, 2.56]
9 Periventricular leukomalacia	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.5 [0.27, 8.43]
10 Retinopathy of prematurity (any stage)	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.27, 3.69]
11 Retinopathy of prematurity (stage 3 or 4)	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.19, 21.06]
12 Necrotising enterocolitis	2	130	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.40, 2.50]
13 Chronic lung disease (at 36 weeks' postmenstrual age)	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.6 [0.85, 3.02]
14 Sepsis	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.51, 1.68]
15 Hospital stay (days)	1	70	Mean Difference (IV, Fixed, 95% CI)	21.0 [‐1.44, 43.44]
16 Oliguria (< 0.5 mL/kg/hour) after onset of treatment	2	120	Risk Ratio (M‐H, Fixed, 95% CI)	1.57 [0.44, 5.63]
17 Gastrointestinal bleed	2	120	Risk Ratio (M‐H, Fixed, 95% CI)	1.5 [0.58, 3.86]
18 Platelet count (x 109/L) after treatment	1	60	Mean Difference (IV, Fixed, 95% CI)	‐29.0 [‐74.83, 16.83]
19 Serum creatinine (µmol/L) after treatment	1	60	Mean Difference (IV, Fixed, 95% CI)	8.84 [‐4.41, 22.09]