title: Indomethacin prophylaxis revisited: changing practice and supportive evidence.
abstract: Important short-term intermediate outcomes such as patent ductus arteriosus (PDA), severe intraventricular haemorrhage, surgical ligation of PDA and serious pulmonary haemorrhage correlate with worse neurosensory outcomes in extreme low birth weight infants. Indomethacin prophylaxis has been shown to significantly prevent such outcomes. However, this positive effect did not translate into neither prevention of bronchopulmonary dysplasia nor long-term neurosensory outcome. The indomethacin prophylaxis story is indeed a puzzling one to neonatal practitioners. We present a summary of evidence and possible explanations to the lack of appreciated long-term effect of indomethacin prophylaxis. As the trial of indomethacin prophylaxis for preterms trial is a major contributor to current evidence, a detailed critical analysis of its methodology is presented. Methodological concerns such as the use of a composite outcome, statistical power, anticipated side effects of indomethacin prophylaxis and lack of predictive validity of cognitive delay measurements are presented.
  
  
  CONCLUSIONS
  Conclusive evidence of indomethacin prophylaxis use in extreme low birth weight infants is still lacking. Future research should put more emphasis on parental preferences, synergistic effect of indomethacin prophylaxis and fluid restriction and early targeted approach to PDA management.
authors.affiliation: Neonatal Intensive Care Unit, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia. kfaleh@ksu.edu.sa
authors.forename: K
authors.initials: K
authors.lastname: AlFaleh
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004374:Ductus Arteriosus, Patent / Q000517:prevention & control*; D019317:Evidence-Based Medicine; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects / Q000627:therapeutic use*; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D010818:Practice Patterns, Physicians' / Q000639:trends
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002317:Cardiovascular Agents; D007213:Indomethacin