title: Prophylactic indomethacin and intestinal perforation in extremely low birth weight infants.
abstract: OBJECTIVE
  Prophylactic indomethacin reduces severe intraventricular hemorrhage but may increase spontaneous intestinal perforation (SIP) in extremely low birth weight (ELBW) infants. Early feedings improve nutritional outcomes but may increase the risk of SIP. Despite their benefits, use of these therapies varies largely by physician preferences in part because of the concern for SIP.
  
  
  METHODS
  This was a cohort study of 15,751 ELBW infants in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from 1999 to 2010 who survived beyond 12 hours after birth. The risk of SIP was compared between groups of infants with and without exposure to prophylactic indomethacin and early feeding in unadjusted analyses and in analyses adjusted for center and for risks of SIP.
  
  
  RESULTS
  Among infants exposed to prophylactic indomethacin, the risk of SIP did not differ between the indomethacin/early-feeding group compared with the indomethacin/no-early-feeding group (adjusted relative risk [RR] 0.74, 95% confidence interval [CI] 0.49-1.11). The risk of SIP was lower in the indomethacin/early-feeding group compared with the no indomethacin/no-early-feeding group (adjusted RR 0.58, 95% CI 0.37-0.90, P = .0159). Among infants not exposed to indomethacin, early feeding was associated with a lower risk of SIP compared with the no early feeding group (adjusted RR 0.53, 95% CI 0.36-0.777, P = .0011).
  
  
  CONCLUSIONS
  The combined or individual use of prophylactic indomethacin and early feeding was not associated with an increased risk of SIP in ELBW infants.
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: John
authors.initials: J
authors.lastname: Kelleher
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Ariel A
authors.initials: AA
authors.lastname: Salas
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Ramachandra
authors.initials: R
authors.lastname: Bhat
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Ambalavanan
authors.affiliation: Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina;
authors.forename: Shampa
authors.initials: S
authors.lastname: Saha
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, and Children's Healthcare of Atlanta, Atlanta, Georgia;
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Stoll
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa;
authors.forename: Edward F
authors.initials: EF
authors.lastname: Bell
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland;
authors.forename: Michele C
authors.initials: MC
authors.lastname: Walsh
authors.affiliation: Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio;
authors.forename: Abbot R
authors.initials: AR
authors.lastname: Laptook
authors.affiliation: Department of Pediatrics, Women & Infants' Hospital, Brown University, Providence, Rhode Island;
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Sánchez
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Seetha
authors.initials: S
authors.lastname: Shankaran
authors.affiliation: Department of Pediatrics, Wayne State University, Detroit, Michigan;
authors.forename: Krisa P
authors.initials: KP
authors.lastname: VanMeurs
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Hale
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland;
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Newman
authors.affiliation: Department of Pediatrics, Wayne State University, Detroit, Michigan;
authors.forename: M Bethany
authors.initials: MB
authors.lastname: Ball
authors.affiliation: Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, California; and.
authors.forename: Abhik
authors.initials: A
authors.lastname: Das
authors.affiliation: Social, Statistical and Environmental Sciences Unit, RTI International, Rockville, Maryland.
authors.forename: Rosemary D
authors.initials: RD
authors.lastname: Higgins
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Myriam
authors.initials: M
authors.lastname: Peralta-Carcelen
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama; wcarlo@peds.uab.edu.
authors.forename: Waldemar A
authors.initials: WA
authors.lastname: Carlo
mesh_terms: D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage*; D052577:Infant, Extremely Low Birth Weight / Q000254:growth & development; D007231:Infant, Newborn; D007416:Intestinal Perforation / Q000175:diagnosis* / Q000517:prevention & control*; D008297:Male; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D007213:Indomethacin
keywords: indomethacin; intestinal perforation; necrotizing enterocolitis; neonate