title: Timing of pharmacological treatment for patent ductus arteriosus and risk of secondary surgery, death or bronchopulmonary dysplasia: a population-based cohort study of extremely preterm infants.
abstract: BACKGROUND
  The optimal timing of pharmacological treatment for patent ductus arteriosus (PDA) in extremely preterm infants is unknown.
  
  
  OBJECTIVE
  To investigate whether timing of pharmacological PDA treatment is associated with a risk of secondary PDA surgery or death before 3 months of age, or bronchopulmonary dysplasia (BPD) in extremely preterm infants.
  
  
  METHODS
  In this population-based cohort of infants born before 27 gestational weeks in Sweden in 2004-2007, 290/585 infants (50%) received pharmacological PDA treatment. Cox proportional hazards regression estimated the hazard ratio (HR, with 95% confidence interval, CI) of secondary PDA surgery or death as a composite outcome in relation to postnatal age at the start of pharmacological treatment: early (0-2 days); intermediate (3-6 days); late (≥7 days). Furthermore, the odds ratio (OR, with 95% CI) of BPD was estimated in relation to postnatal age at PDA treatment by conditional logistic regression.
  
  
  RESULTS
  The median postnatal age at the start of pharmacological PDA treatment was 4 days. 102 infants had secondary PDA surgery. Timing of PDA treatment was not associated with risk of PDA surgery or death; adjusted HRs were 0.89 (95% CI 0.57-1.39) after an intermediate start and 1.10 (95% CI 0.53-2.28) after a late start, compared to an early start of treatment. Compared to the early start of PDA treatment, the intermediate start was not associated with any risk of BPD, while late PDA treatment was associated with a lower BPD risk; adjusted ORs were 0.83 (95% CI 0.42-1.64) and 0.28 (95% CI 0.13-0.61), respectively.
  
  
  CONCLUSIONS
  Timing of pharmacological PDA treatment after extremely preterm birth is not associated with the risk of secondary PDA surgery or death. Moreover, expectant PDA management is not associated with an increased risk of BPD.
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Gudmundsdottir
authors.forename: Stefan
authors.initials: S
authors.lastname: Johansson
authors.forename: Stellan
authors.initials: S
authors.lastname: Håkansson
authors.forename: Mikael
authors.initials: M
authors.lastname: Norman
authors.forename: Karin
authors.initials: K
authors.lastname: Källen
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Bonamy
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control*; D015331:Cohort Studies; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D005260:Female; D005865:Gestational Age; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use*; D062071:Infant, Extremely Premature / Q000502:physiology*; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D013548:Sweden; D061665:Time-to-Treatment
chemical_list: D016861:Cyclooxygenase Inhibitors; D007052:Ibuprofen; D007213:Indomethacin