Oral Ibuprofen versus Intravenous Ibuprofen or Intravenous Indomethacin for the Treatment of Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-AnalysisNeumann 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
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.
The results of the first study comparing efficacy and safety of oral versus IV ibuprofen for PDA closure in extremely low birth weight infants have just been published . Inclusion of the data into our meta-analysis resulted in only marginal changes and did not alter the overall conclusion. Failure of primary PDA closure was lower after treatment with oral, as compared with IV ibuprofen [n = 236, RR 0.42 (95% CI 0.26, 0.67); RD –0.22 (95% CI –0.35, –0.11); NNT 5 (95% CI 3, 9)] while rates of gastrointestinal side effects were similar (necrotizing enterocolitis: n = 236, RR 0.65 (95% CI 0.38, 1.13), gastrointestinal bleeding: n = 236, RR 2.94 (95% CI 0.31, 27.70), gastrointestinal perforation: n = 236, RR 0.32 (95% CI 0.01, 7.48).
1 Erdeve O, Yurttutan S, Altug N, Ozdemir R, Gokmen T, Dilmen U, Oguz SS, Uras N: Oral versus intravenous ibuprofen for patent ductus arteriosus closure: a randomised controlled trial in extremely low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2011 (DOI: 10.1136/archdischild-2011-300532).
Dr. Roland Neumann, MD
Department of Neonatology
Basel University Children’s Hospital (UKBB)
Spitalstrasse 21, CH–4031 Basel (Switzerland)
Tel. +41 61 265 9564, E-Mail firstname.lastname@example.org
Received: June 30, 2011
Accepted after revision: November 24, 2011
Published online: March 8, 2012
Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 4, Number of References : 28
Neonatology (Fetal and Neonatal Research)
Vol. 102, No. 1, Year 2012 (Cover Date: June 2012)
Journal Editor: Halliday H.L. (Belfast), Speer C.P. (Würzburg)
ISSN: 1661-7800 (Print), eISSN: 1661-7819 (Online)
For additional information: http://www.karger.com/NEO