title: Timing of patent ductus arteriosus treatment and respiratory outcome in premature infants: a double-blind randomized controlled trial.
abstract: OBJECTIVE
  To determine whether "early" ibuprofen treatment, at the onset of subtle patent ductus arteriosus (PDA) symptoms, would improve respiratory outcome in premature infants compared with "expectant" management, with ibuprofen treatment only when the PDA becomes hemodynamically significant (HS).
  
  
  METHODS
  We conducted a randomized double-blind controlled trial of infants with gestational ages 23 to 32 weeks and birth weights 500 to 1250 g who had echocardiography for subtle PDA symptoms (metabolic acidosis, murmur, bounding pulses). Infants were then randomized to "early" treatment (blinded ibuprofen; n = 54) or "expectant management" (blinded placebo, n = 51). If the PDA became HS (pulmonary hemorrhage, hypotension, respiratory deterioration), infants received open label ibuprofen. Infants with HS PDA at enrollment were excluded from the study. Respiratory outcomes and mortality and major morbidities were determined.
  
  
  RESULTS
  "Early" treatment infants received ibuprofen at median age of 3 days; infants in the "expectant group" in whom HS symptoms developed (20%) received ibuprofen at median of 11 days. A total of 49% of "expectant" infants never required ibuprofen or ligation. No significant differences were found in the primary outcome (days on oxygen [O(2)] during the first 28 days), death, O(2) at 36 weeks, death or O(2) at 36 weeks, intestinal perforation, surgical necrotizing enterocolitis, grades III and IV intracranial hemorrhage, periventricular leukomalacia, sepsis or retinopathy of prematurity.
  
  
  CONCLUSIONS
  Infants with mild signs of PDA do not benefit from early PDA treatment compared with delayed treatment.
authors.affiliation: Department of Pediatrics, University of Miami, Miami, FL, USA. isosenko@miami.edu
authors.forename: Ilene R S
authors.initials: IR
authors.lastname: Sosenko
authors.forename: M Florencia
authors.initials: MF
authors.lastname: Fajardo
authors.forename: Nelson
authors.initials: N
authors.lastname: Claure
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bancalari
mesh_terms: D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000627:therapeutic use*; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D011446:Prospective Studies; D012119:Respiration / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016861:Cyclooxygenase Inhibitors; D007052:Ibuprofen