Comparison 3. Intravenous or oral ibuprofen versus intravenous or oral indomethacin.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to close a patent ductus arteriosus (PDA) (after single or 3 doses)	24	1590	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.92, 1.24]
2 All‐cause mortality	10	697	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.54, 1.17]
3 Neonatal mortality (during first 28/30 days of life)	4	333	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.59, 2.11]
4 Reopening of the ductus arteriosus	7	305	Risk Ratio (M‐H, Fixed, 95% CI)	1.57 [0.83, 2.99]
5 Need for surgical closure of the PDA	16	1275	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.81, 1.39]
6 Need for re‐treatment with indomethacin or ibuprofen to close the PDA	7	241	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [0.76, 1.90]
7 Duration of ventilator support (days)	6	471	Mean Difference (IV, Fixed, 95% CI)	‐2.35 [‐3.71, ‐0.99]
8 Duration of need for supplementary oxygen (days)	6	556	Mean Difference (IV, Fixed, 95% CI)	‐0.33 [‐1.66, 0.99]
9 Pulmonary haemorrhage	4	303	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.40, 2.04]
10 Pulmonary hypertension	2	118	Risk Ratio (M‐H, Fixed, 95% CI)	3.53 [0.15, 81.11]
11 Chronic lung disease (at 28 days)	5	292	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [0.93, 1.55]
12 Chronic lung disease (at 36 weeks' postmenstrual age)	3	357	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.77, 1.61]
13 Chronic lung disease (age not stated)	3	225	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.82, 1.12]
14 Intraventricular haemorrhage (any grade)	7	524	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.61, 1.31]
15 Intraventricular haemorrhage (grades III and IV)	10	798	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.68, 1.63]
16 Periventricular leukomalacia (cystic)	6	573	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.67, 2.30]
17 Necrotising enterocolitis (any stage)	18	1292	Risk Ratio (M‐H, Fixed, 95% CI)	0.68 [0.49, 0.94]
18 Intestinal perforation	5	255	Risk Ratio (M‐H, Fixed, 95% CI)	0.48 [0.20, 1.14]
19 Gastrointestinal bleed	7	514	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.55, 1.61]
20 Time to full enteral feeds	4	413	Mean Difference (IV, Fixed, 95% CI)	0.70 [‐1.89, 3.29]
21 Time to regain birth weight (days)	2	188	Mean Difference (IV, Fixed, 95% CI)	‐0.18 [‐2.59, 2.22]
22 Retinopathy of prematurity	7	581	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.60, 1.10]
23 Sepsis	7	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.84, 1.76]
24 Oliguria (urine output < 1 mL/kg/hour)	6	576	Risk Ratio (M‐H, Fixed, 95% CI)	0.28 [0.14, 0.54]
25 Serum/plasma creatinine levels (μmol/L) 72 hours after treatment	11	918	Mean Difference (IV, Fixed, 95% CI)	‐8.12 [‐10.81, ‐5.43]
26 Increase in serum/plasma creatinine levels (mg/dL) following treatment	1	21	Mean Difference (IV, Fixed, 95% CI)	‐15.91 [‐31.78, ‐0.04]
27 Duration of hospitalisation (days)	4	368	Mean Difference (IV, Fixed, 95% CI)	‐0.69 [‐4.54, 3.16]
28 Significant decrease in urine output (> 20% decrease in urine output after starting therapy)	1	144	Risk Ratio (M‐H, Fixed, 95% CI)	0.51 [0.30, 0.87]
29 Daily urine output mL/kg/hr	1	200	Mean Difference (IV, Fixed, 95% CI)	0.59 [0.45, 0.73]
30 Serum bilirubin (µmol/L) after treatment	1	200	Mean Difference (IV, Fixed, 95% CI)	12.65 [9.96, 15.34]
31 Platelet count (x109/L)	1	200	Mean Difference (IV, Fixed, 95% CI)	72.0 [58.07, 85.93]