14. Interventions for symptomatic PDA: retinopathy of prematurity.

		Comparison
		Indomethacin	Ibuprofen	Placebo/no treatment
Therapy	Indomethacin	Prolonged vs short course* Any stage ROP 1.04, 95% CI 0.57 to 1.88; 3 RCTs, N = 240	‐	Indomethacin vs placebo/no treatment* Any stage ROP 0.32, 95% CI 0.07 to 1.42; 1 RCT, N = 47 Severe ROP 0.96, 95% CI 0.06 to 14.43; 1 RCT, N = 47
				Very early treatment (≤ day 3) vs expectant management* Severe ROP 0.16, 95% CI 0.01 to 2.93; 2 RCTs, N = 136
				Early treatment (≤ day 7) vs expectant management* Severe ROP 0.30, 95% CI 0.02 to 5.34; 1 RCT, N = 41
	Ibuprofen	Ibuprofen IV/PO vs indomethacin IV/PO* Any stage ROP 0.81, 95% CI 0.60 to 1.10; 7 RCTs, N = 581	Ibuprofen PO vs Ibuprofen IV* ROP requiring laser treatment 0.59, 95% CI 0.26 to 1.34; 2 RCTs, N = 172	Ibuprofen IV vs placebo/no treatment* Any stage ROP 1.19, 95% CI 0.88 to 1.62; 1 RCT, N = 129 Severe ROP 1.18, 95% CI 0.38 to 3.68; 1 RCT, N = 129
			Ibuprofen high‐dose vs standard‐dose* Any stage ROP 1.00, 95% CI 0.27 to 3.69; 1 RCT, N = 70 Severe ROP 2.00, 95% CI 0.19 to 21.06; 1 RCT, N = 70
		Ibuprofen PO vs indomethacin IV/PO* Any stage ROP RD 0.00, 95% CI ‐0.18 to 0.17; 2 RCTs, N = 71	Ibuprofen IV: echocardiography‐guided vs standard administration* ROP requiring laser treatment 2.25, 95% CI 0.50 to 10.05; 1 RCT, N = 49	Very early treatment (≤ day 3) vs expectant management* Severe ROP 0.80, 95% CI 0.24 to 2.69; 1 RCT, N = 60
			Ibuprofen IV: continuous infusion vs intermittent bolus* Any stage ROP 0.68, 95% CI 0.39 to 1.19; 1 RCT, N = 111 Severe ROP 0.34, 95% CI 0.04 to 3.16; 1 RCT, N = 111	Early treatment (≤ day 7) vs expectant management* Severe ROP 1.65, 95% CI 0.51 to 5.31; 1 RCT, N = 105
	Acetaminophen	Severe ROP 1.32, 95% CI 0.58 to 2.99; 2 RCTs, N = 96	Severe ROP 0.43, 95% CI 0.12 to 1.55; 2 RCTs, N = 191 ROP requiring laser treatment 0.94, 95% CI 0.48 to 1.85; 3 RCTs, N = 353	Late treatment (≥ day 14) ROP requiring treatment 3.11, 95% CI 0.34 to 28.09; 1 RCT, N = 55
	Surgicalligation	3.8, 95% CI 1.12 to 12.93; 1 RCT, N = 154	‐	‐

CI confidence interval;IV: intravenous; PO: per os; PDA: patent ductus arteriosus; PMA: post‐menstrual age; RCT: randomised controlled trials; RD: risk difference; ROP: retinopathy of prematurity; vs: versus

Reference is the listed comparison therapy, unless otherwise indicated by *

Differences between intervention and comparison provided as risk ratio (RR), unless otherwise specified

Severe ROP refers to stage ≥ 3