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Oral Ibuprofen versus Intravenous Ibuprofen or Intravenous Indomethacin for the Treatment of Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis

Neumann R.a, b · Schulzke S.M.a, b · Bührer C.c
aDepartment of Neonatology, Basel University Children’s Hospital, Basel, Switzerland; bNeonatal Clinical Care Unit, King Edward Memorial Hospital for Women, Perth, W.A., Australia; cDepartment of Neonatology, Charité University Medical Center, Berlin, Germany Neonatology 2012;102:9–15 (DOI:10.1159/000335332)


Background: Pharmacological closure of patent ductus arteriosus (PDA) is commonly achieved by intravenous (IV) administration of ibuprofen or indomethacin. Occasionally, oral ibuprofen is used for PDA treatment although its efficacy and safety are unclear. Objectives: To systematically review randomized and quasi-randomized trials comparing oral ibuprofen with IV ibuprofen or IV indomethacin for closure of PDA in preterm infants. Methods: The standard search methods of the Cochrane Neonatal Review Group were used. Results: We identified two studies (n = 166) of good methodological quality comparing oral ibuprofen with IV ibuprofen and three small trials (n = 92) of moderate methodological quality comparing oral ibuprofen to IV indomethacin. Meta-analysis showed higher PDA closure rate of oral ibuprofen versus IV ibuprofen but no difference between oral ibuprofen and IV indomethacin. Meta-analysis did not indicate a significant difference in adverse effects. Conclusion: Oral ibuprofen for PDA closure appears to be as effective as IV ibuprofen and IV indomethacin. Due to small sample size, lack of data in extremely preterm neonates, and methodological limitations of reviewed trials, definitive conclusions cannot be drawn. Randomized trials with a low risk of bias and adequate sample size in extremely preterm infants are urgently needed.


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