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Network meta-analysis of indomethacin versus ibuprofen versus placebo for PDA in preterm infants
L J Jones1, P D Craven, J Attia
1Neonatal Intensive Care Unit, John Hunter Children's Hospital, Lookout Road, New Lambton, Australia. sj286153@bigpond.net.au
Insights
Indomethacin and ibuprofen effectively close patent ductus arteriosus (PDA) in preterm infants. However, ibuprofen may increase the risk of chronic lung disease, and more research is needed on long-term outcomes.
Area of Science:
- Neonatalogy
- Pharmacology
- Clinical Trials
Background:
- Patent ductus arteriosus (PDA) is common in preterm infants.
- Effective treatment for PDA is crucial to reduce infant morbidity and mortality.
Purpose of the Study:
- To compare the efficacy and safety of indomethacin and ibuprofen versus placebo for PDA closure in preterm infants.
- To evaluate the impact of these treatments on infant morbidity and mortality.
Main Methods:
- Systematic review and network meta-analysis of randomized controlled trials.
- Included studies compared intravenous indomethacin, ibuprofen, or placebo for PDA in preterm infants.
Main Results:
- Both indomethacin and ibuprofen significantly increased PDA closure rates compared to placebo.
- Ibuprofen was associated with a higher risk of chronic lung disease compared to indomethacin and placebo.
- No significant differences were found in risks of intraventricular hemorrhage, necrotizing enterocolitis, or death between groups.
Conclusions:
- Indomethacin and ibuprofen promote PDA closure in preterm infants.
- Ibuprofen treatment may elevate the risk of chronic lung disease.
- High-quality evidence on neurodevelopmental outcomes and long-term effects is needed.
Objectives:
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.
Data Sources:
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.
Review 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.