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Spontaneous intestinal perforation in extremely low birth weight infants: association with indometacin therapy and effects on neurodevelopmental outcomes at 18–22 months corrected age
  1. Rajan Wadhawan1,
  2. William Oh2,
  3. Betty R Vohr2,
  4. Shampa Saha3,
  5. Abhik Das4,
  6. Edward F Bell5,
  7. Abbott Laptook2,
  8. Seetha Shankaran6,
  9. Barbara J Stoll7,
  10. Michele C Walsh8,
  11. Rose Higgins9
  1. 1Division of Neonatology, All Children's Hospital, St Petersburg, Florida, USA
  2. 2Department of Pediatrics, Women & Infants Hospital, Providence, Rhode Island, USA
  3. 3Department of Statistics and Epidemiology, Research Triangle Institute, Research Triangle Park, North Carolina, USA
  4. 4RTI International, Rockville, Maryland, USA
  5. 5Department of Pediatrics, University of Iowa, Iowa city, Iowa, USA
  6. 6Department of Pediatrics, Wayne State UniversityChildrens Hospital of Michigan, Detroit, Michigan, USA
  7. 7Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA
  8. 8Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA
  9. 9Eunice Kennedy Shiver National Institute of Child Health and Human Development, Bethesda, Maryland, USA
  1. Correspondence to Rajan Wadhawan, Center for Neonatal Care, Florida Hospital for Children, Orlando, FL 32804; Rajan.Wadhawan.MD{at}


Background Spontaneous intestinal perforation (SIP) is associated with the use of postnatal glucocorticoids and indometacin in extremely low birth weight (ELBW) infants. The authors hypothesised: 1) an association of SIP with the use of antenatal steroids (ANS) and indometacin either as prophylaxis for intraventricular hemorrhage (IVH) (P Indo) or for treatment of PDA (Indo/PDA) and 2) an increased risk of death or abnormal neurodevelopmental outcomes in infants with SIP at 18–22 months corrected age.

Design/Methods The authors retrospectively identified ELBW infants with SIP in the Neonatal Research Network's generic database. Unadjusted analysis identified the differences in maternal, neonatal and clinical variables between infants with and without SIP. Logistic regression analysis identified the adjusted OR for SIP with reference to ANS, P Indo and Indo/PDA. Neurodevelopmental outcomes were assessed among survivors at 18–22 months corrected age.

Results Indo/PDA was associated with an increased risk of SIP (adjusted OR 1.61; 95% CI 1.25 to 2.08), while P Indo and ANS were not. SIP was independently associated with an increased risk of death or neurodevelopmental impairment (NDI) (adjusted OR 1.85; 95% CI 1.32 to 2.60) and NDI among survivors (adjusted OR 1.75, 95% CI 1.20 to 2.55).

Conclusion Indometacin used for IVH prophylaxis and ANS were not associated with the occurrence of SIP in ELBW infants. Indometacin used for treatment of symptomatic PDA was however associated with an increased risk of SIP. ELBW infants with SIP have an increased risk of poor neurodevelopmental outcomes.

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  • Funding National Institute of Child Health & Human Development.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.