title: Factors associated with non-response to second course indomethacin for PDA treatment in preterm neonates.
abstract: BACKGROUND
  Failure of first course of indomethacin (FCI) for patent ductus arteriosus (PDA) treatment in preterm neonates often prompts clinicians to consider a second course (SCI).
  
  
  OBJECTIVE
  To identify factors including baseline characteristics and response to FCI that are associated with non-response to SCI for PDA treatment in preterm neonates.
  
  
  METHODS
  In this retrospective observational study, neonates ≤32 weeks admitted to a tertiary NICU over 5 years who received two indomethacin courses for PDA treatment were reviewed. Only neonates with echocardiograms (ECHO) immediately before and after receipt of each indomethacin course were included. Primary outcome was non-response to SCI. Baseline characteristics and response to FCI were compared between responders and non-responders of SCI.
  
  
  RESULTS
  Of the 98 neonates enrolled, 47 (48%) had non-response to SCI. Of them, 27 patients (57%) had prior non-response to FCI, while of the 51 neonates who responded to SCI, 24 neonates (47%) had prior non-response to FCI. The adjusted risk of non-response to SCI in patients who had non-response to FCI was 37% higher (relative risk = 1.37, 95%CI: 0.87-1.80; p = .07) compared to those who had response to FCI. Multivariable analysis showed that increasing gestational age (AOR: 1.6, 95%CI: 1.1-2.3, p = .03) was associated with a higher odds of non-response to SCI while the odds of non-response to SCI increased by 90% in patients with non-response to FCI (AOR: 1.9, 95%CI: 0.8-4.5; p = .15) compared to those with success of FCI, although no statistical significance was observed.
  
  
  CONCLUSIONS
  Advanced gestational age was the predictor of non-response to SCI in preterm neonates.
authors.affiliation: a Department of Pediatrics , University of Toronto , Toronto , Canada.
authors.forename: Deepak
authors.initials: D
authors.lastname: Louis
authors.affiliation: b Mount Sinai Hospital , Toronto , Canada.
authors.forename: Cindy
authors.initials: C
authors.lastname: Wong
authors.affiliation: c MiCare Research Center, Mount Sinai Hospital , Toronto , Canada.
authors.forename: Xiang Y
authors.initials: XY
authors.lastname: Ye
authors.affiliation: d Division of Neonatology, Department of Pediatrics , The Hospital for Sick Children, University of Toronto , Toronto , Canada.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: McNamara
authors.affiliation: e Department of Pediatrics , Mount Sinai Hospital, University of Toronto , Toronto , Canada.
authors.forename: Amish
authors.initials: A
authors.lastname: Jain
mesh_terms: D002317:Cardiovascular Agents / Q000008:administration & dosage*; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage*; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D012189:Retrospective Studies; D017211:Treatment Failure
chemical_list: D002317:Cardiovascular Agents; D007213:Indomethacin
keywords: Indomethacin; failure; patent ductus arteriosus; preterm; second course