A Cochrane review included 19 studies with a total of 2 872 infants. Most participants were very low birth weight (less than 1 500 grams), but the largest single trial restricted participation to extremely low birth weight infants (less than 1 000 grams; n=1 202). All the studies used prophylactic intravenous indomethacin as treatment. The dosage schedules varied from a single dose of 0.2 mg/kg at 24 hours of age to a daily dose of 0.1 mg/kg given for six days. A placebo, typically saline, was used as control in all trials apart from one.
The incidence of symptomatic patent ductus arteriosus (PDA) (RR 0.44, 95% CI 0.38 to 0.50; 14 studies, n=2 193) and PDA surgical ligation (RR 0.51, 95% CI 0.37 to 0.71; 8 studies, n=1 791) was significantly lower in treated infants. Prophylactic indomethacin also significantly reduced the incidence of severe intraventricular haemorrhage (RR 0.66, 95% CI 0.53 to 0.82; 14 studies, n= 2 588). Meta-analyses found no evidence of an effect on mortality (RR 0.96, 95% CI 0.81 to 1.12; 18 studies, n= 2 769) or on a composite of death or severe neurodevelopmental disability assessed at 18 to 36 months old (RR 1.02, 95% CI 0.90 to 1.15; 3 studies, n= 1 491).