title: Oral ibuprofen versus intravenous ibuprofen or intravenous indomethacin for the treatment of patent ductus arteriosus in preterm infants: a systematic review and meta-analysis.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neonatology, Basel University Children's Hospital, Basel, Switzerland. roland.neumann@ukbb.ch
authors.forename: Roland
authors.initials: R
authors.lastname: Neumann
authors.forename: Sven M
authors.initials: SM
authors.lastname: Schulzke
authors.forename: Christoph
authors.initials: C
authors.lastname: Bührer
mesh_terms: D000284:Administration, Oral; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy*; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage*; D007213:Indomethacin / Q000008:administration & dosage*; D007231:Infant, Newborn; D007234:Infant, Premature; D007262:Infusions, Intravenous; D016032:Randomized Controlled Trials as Topic
chemical_list: D016861:Cyclooxygenase Inhibitors; D007052:Ibuprofen; D007213:Indomethacin