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Effects of indomethacin prophylaxis timing on intraventricular haemorrhage and patent ductus arteriosus in extremely low birth weight infants
  1. Hussnain Mirza1,
  2. Abbot R Laptook2,
  3. William Oh2,
  4. Betty R Vohr2,
  5. Barbara J Stoll3,
  6. Sarah Kandefer4,
  7. Barbara S Stonestreet2,
  8. and Generic Database Subcommittee of the NICHD Neonatal Research Network
  1. 1Center for Neonatal Care, Florida Hospital for Children/UCF College of Medicine, Orlando, Florida, USA
  2. 2Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, USA
  3. 3Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA
  4. 4Research Statistician at RTI International/Neonatal Research Network, Research Triangle Park, North Carolina, USA
  1. Correspondence to Dr Hussnain Mirza, UCF College of Medicine, Center for Neonatal Care, Florida Hospital for Children, 601 E Rollins St., Orlando, FL 32803, USA; Hussnain.Mirza.MD{at}


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.

  • Neonatology
  • Intraventricular Hemorrhage
  • Patent Ductus Arteriosus
  • Extreme prematurity

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