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Arch Dis Child Fetal Neonatal Ed. 2016 Sep;101(5):F418-22. doi: 10.1136/archdischild-2015-309112. Epub 2016 Jan 5.

Effects of indomethacin prophylaxis timing on intraventricular haemorrhage and patent ductus arteriosus in extremely low birth weight infants.

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Center for Neonatal Care, Florida Hospital for Children/UCF College of Medicine, Orlando, Florida, USA.
Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, USA.
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
Research Statistician at RTI International/Neonatal Research Network, Research Triangle Park, North Carolina, USA.



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.


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.


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).


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.


Extreme prematurity; Intraventricular Hemorrhage; Neonatology; Patent Ductus Arteriosus

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