title: Effect of prophylactic indomethacin administration and early feeding on spontaneous intestinal perforation in extremely low-birth-weight infants.
abstract: To determine the effect of concomitant administration of prophylactic indomethacin and early enteral feeds on the risk of spontaneous intestinal perforation (SIP) in extremely low-birth-weight (ELBW) infants, and to describe the variation in prophylactic indomethacin use in Canada.
  
  
  
  A retrospective cohort study of 4268 ELBW infants born at <30 weeks' gestation admitted to Canadian neonatal units between 2010 and 2014 was conducted. Prophylactic indomethacin (I+ or I-, administered within 24 h) and early feeding (E+ or E-, initiated in the first 2 days) exposures were studied concurrently and independently. The primary outcomes were SIP and death before discharge. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated.
  
  
  
  Compared with the I-/E+ reference group (n=1829), infants in I+/E+ (n=285; aOR 2.92, 95% CI 1.41 to 6.08) and I+/E- (n=213; aOR 2.84, 95% CI 1.35 to 5.98) groups had higher odds of SIP, whereas those in the I-/E- group had similar odds (n=1941; aOR 1.37, 95% CI 0.88 to 2.14). Odds of SIP were higher in the indomethacin exposed group (I+) compared with the unexposed (I-) group when controlled for early feeding (aOR 2.43, 95% CI 1.41 to 4.19), but not in the early feeding group when controlled for indomethacin. The use of prophylactic indomethacin ranged from 0% usage in 13 sites to 78% use in one site.
  
  
  
  Prophylactic indomethacin was associated with increased odds of SIP independently from early feeding in this cohort; however, early enteral feeding was not associated with SIP. Marked variation in the use of prophylactic indomethacin was identified.
authors.affiliation: Neonatal Intensive Care Unit, Royal Columbian Hospital, New Westminster, BC, Canada.|Department of Paediatrics, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Stavel
authors.affiliation: Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Wong
authors.affiliation: Neonatal Intensive Care Unit, Royal Columbian Hospital, New Westminster, BC, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Cieslak
authors.affiliation: Neonatal Intensive Care Unit, Surrey Memorial Hospital, Surrey, BC, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Sherlock
authors.affiliation: Department of Pediatrics, McGill University Health Centre, Montreal, QC, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Claveau
authors.affiliation: Department of Paediatrics, Mount Sinai Hospital, Toronto, ON, Canada.|Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
authors.forename: P S
authors.initials: PS
authors.lastname: Shah
mesh_terms: D002170:Canada / Q000453:epidemiology; D000074042:Cerebral Intraventricular Hemorrhage / Q000453:epidemiology* / Q000517:prevention & control; D016208:Databases, Factual; D004750:Enteral Nutrition; D005260:Female; D005865:Gestational Age; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage* / Q000009:adverse effects; D052577:Infant, Extremely Low Birth Weight; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007416:Intestinal Perforation / Q000453:epidemiology*; D008297:Male; D010351:Patient Discharge / Q000706:statistics & numerical data; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D007213:Indomethacin