Network meta-analysis of indomethacin versus ibuprofen versus placebo for PDA in preterm infants.
OBJECTIVE
To evaluate the effects of indomethacin or ibuprofen compared with placebo on closure, morbidity and mortality in preterm infants <37 weeks' gestation with echocardiographically and/or clinically important patent ductus arteriosus (PDA) at >24 h of life.


METHODS
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, Cochrane Library, clinicaltrials.gov, controlled-trials.com, American Pediatric and European Paediatric Research Societies and Effective Care of the Newborn Infant.


METHODS
Systematic review with network meta-analysis of randomised studies comparing intravenous indomethacin, ibuprofen or placebo for PDA in preterm infants at >24 h of life.


RESULTS
Ten trials compared intravenous indomethacin versus intravenous ibuprofen, nine intravenous indomethacin versus placebo and one intravenous ibuprofen versus placebo. Both intravenous indomethacin (pooled RR 2.39 (95% CI 2.05 to 2.78)) and intravenous ibuprofen (RR 2.40 (95% CI 2.03 to 2.84)) closed a PDA more effectively than placebo. Intravenous ibuprofen was associated with approximately 30% greater risk of chronic lung disease than intravenous indomethacin (RR 1.28 (95% CI 1.03 to 1.60)) or placebo (RR 1.29 (95% CI 0.99 to 1.70)). Differences in risk or benefit were not significant between any combination of intravenous indomethacin, intravenous ibuprofen or placebo groups for intraventricular haemorrhage, necrotising enterocolitis and death. Reporting on neurological outcomes was insufficient for pooling.


CONCLUSIONS
Intravenous indomethacin or ibuprofen administered to preterm infants for PDA at >24 h of life promoted ductal closure, but other short-term benefits were not seen. Treatment with intravenous ibuprofen may increase the risk of chronic lung disease. Good-quality evidence of treatment effect on morbidity, mortality and improved neurodevelopment is urgently needed.
Jones
L J
LJ
Neonatal Intensive Care Unit, John Hunter Children's Hospital, Lookout Road, New Lambton, Australia. sj286153@bigpond.net.au
Craven
P D
PD
Attia
J
J
Thakkinstian
A
A
Wright
I
I
D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D002317:Cardiovascular Agents / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy; D007052:Ibuprofen / Q000627:therapeutic use; D007213:Indomethacin / Q000627:therapeutic use; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D002317:Cardiovascular Agents; D016861:Cyclooxygenase Inhibitors; D007052:Ibuprofen; D007213:Indomethacin