title: Effects of indomethacin prophylaxis timing on intraventricular haemorrhage and patent ductus arteriosus in extremely low birth weight infants.
abstract: OBJECTIVE
  Indomethacin prophylaxis (IP) reduces the risk of intraventricular haemorrhage (IVH) and patent ductus arteriosus (PDA) in preterm infants. However, the optimal time to administer IP has not been determined. We hypothesised that IP at ≤6 h is associated with a lower incidence of IVH or death than if administered at >6-24 h of age.
  
  
  METHODS
  We performed a retrospective cohort study of extremely low birth weight infants (≤1000 g birth weight) treated in the neonatal intensive care units in the Neonatal Research Network from 2003 to 2010 and who received IP in the first 24 h of age. Infants were dichotomised based upon receipt of IP at ≤6 or >6-24 h of age. The primary outcomes were IVH alone and IVH or death. Secondary outcomes were PDA alone and PDA or death. We used multivariable analyses to determine associations between the age of IP and the study outcomes expressed as an OR and 95% CI.
  
  
  RESULTS
  IP was given at ≤6 h to 2340 infants and at >6-24 h to 1915 infants. Infants given IP at ≤6 h had more antenatal steroid exposure, more inborn and less cardiopulmonary resuscitation (p<0.01). After multivariable analyses, age of IP receipt was not associated with IVH, and IVH or death but PDA receiving treatment/ligation or death was lower among IP at ≤6 h compared with IP at >6-24 h (OR 0.83, 95% CI 0.71 to 0.98).
  
  
  CONCLUSIONS
  IP at ≤6 h of age is not associated with less IVH or death, but is associated with less PDA receiving treatment/ligation or death.
authors.affiliation: Center for Neonatal Care, Florida Hospital for Children/UCF College of Medicine, Orlando, Florida, USA.
authors.forename: Hussnain
authors.initials: H
authors.lastname: Mirza
authors.affiliation: Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, USA.
authors.forename: Abbot R
authors.initials: AR
authors.lastname: Laptook
authors.affiliation: Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, USA.
authors.forename: William
authors.initials: W
authors.lastname: Oh
authors.affiliation: Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, USA.
authors.forename: Betty R
authors.initials: BR
authors.lastname: Vohr
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Stoll
authors.affiliation: Research Statistician at RTI International/Neonatal Research Network, Research Triangle Park, North Carolina, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kandefer
authors.affiliation: Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, USA.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Stonestreet
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002543:Cerebral Hemorrhage / Q000517:prevention & control*; D004334:Drug Administration Schedule; D004374:Ductus Arteriosus, Patent / Q000517:prevention & control*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage*; D062071:Infant, Extremely Premature; D015931:Intensive Care, Neonatal / Q000379:methods; D008297:Male; D012189:Retrospective Studies
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin
keywords: Extreme prematurity; Intraventricular Hemorrhage; Neonatology; Patent Ductus Arteriosus