title: Variation and comparative effectiveness of patent ductus arteriosus pharmacotherapy in extremely low birth weight infants.
abstract: BACKGROUND
  Patent ductus arteriosus (PDA) occurs in 70% of extremely low birth weight (ELBW, birth weight <1000 g) infants. Approximately 34% of ELBW infants with a PDA have spontaneous closure. Failure of the ductus arteriosus to close has been associated with multiple morbidities.
  
  
  OBJECTIVE
  To examine variability over time and across hospitals in early therapeutic (2-7 day) use of indomethacin (INDO) vs ibuprofen (IBU) for PDA treatment in outborn ELBW infants and examine the outcomes and side effects of both pharmacological agents in this population.
  
  
  METHODS
  Data were extracted from the Pediatric Health Information System. ELBW infants born between January 1, 2007 and December 31, 2010 and admitted on day of life 0 were eligible for inclusion. 732 infants had a PDA diagnosis and met inclusion criteria. We explored the variability in PDA pharmacotherapy over time and across hospitals. We compared outcomes of both agents for in-hospital mortality, need for surgical ligation, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leukomalacia, renal failure, and persistent pulmonary hypertension. Statistical methods included chi square and multivariable regression analysis. Instrumental variable analysis was used to control for selection bias and omitted variables.
  
  
  RESULTS
  There was large variability in PDA pharmacotherapy over time and across hospitals. INDO use declined as IBU use grew from 12.8 to 38.9%. There was no difference in hospital or NICU characteristics between high and low IBU using NICUs. Renal failure was more common in infants receiving INDO compared to IBU.
  
  
  CONCLUSIONS
  We noted large variability in PDA pharmacotherapy. Renal failure was more common with INDO use. Until further studies to compare the long-term effects of both drugs, our data support IBU as the preferred medication for PDA pharmacotherapy in ELBW infants.
authors.affiliation: University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USA.
authors.forename: N O
authors.initials: NO
authors.lastname: ElHassan
authors.affiliation: Department of Health Policy & Management, College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Bird
authors.affiliation: Center for Health Decision Science, Department of Health Policy and Management, Harvard School of Public Health, Boston, MA, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: King
authors.affiliation: Cancer Center Statistics, Mayo Clinic, Rochester, MN, USA.
authors.forename: P B
authors.initials: PB
authors.lastname: Ambadwar
authors.affiliation: Section of Surgery and Pediatrics, Duke Children's Hospital, Durham, NC, USA.
authors.forename: R D B
authors.initials: RD
authors.lastname: Jaquiss
authors.affiliation: Section of Neonatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Kaiser
authors.affiliation: Department of Pediatrics and Psychiatry, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Robbins
mesh_terms: D015331:Cohort Studies; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use*; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy*; D008297:Male; D012044:Regression Analysis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D016861:Cyclooxygenase Inhibitors; D007052:Ibuprofen; D007213:Indomethacin
keywords: Patent ductus arteriosus; extremely low birth weight infants; ibuprofen; indomethacin