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Neonatal Necrotizing Enterocolitis With Intestinal Perforation in Extremely Premature Infants Receiving Early Indomethacin Treatment for Patent Ductus Arteriosus

Abstract

Survival of extremely premature infants (<27 weeks' gestational age) has improved over the past two decades. Indomethacin prophylaxis was used in these infants, who have the highest mortality and morbidity rates, to reduce the incidence of intraventricular hemorrhage and patent ductus arteriosus (PDA). Medical records of 65 extremely premature infants born at our institution between 1995 and 2001 were reviewed retrospectively to determine whether treatment of PDA with indomethacin in the first 48 hours of life reduces the need for PDA ligation or increases neonatal morbidity, when compared to treatment begun later. Thirty infants in the early treatment group (ETG) were treated during the first 48 hours after birth, and 32 infants in the standard treatment group (STG) were managed expectantly for PDA. Three infants died in the first hours of life and were eliminated from further analysis. ETG infants were 24.9±1.1 (mean±SD) weeks' gestation with a birth weight of 678±143 g. STG infants were 25.3±1.1 weeks (NS) and 730±125 g (NS). Hemodynamically significant PDA was diagnosed or confirmed by echocardiography in 19 ETG patients and 17 STG patients. Of the patients with hemodynamically significant PDA, 1 (5%) ETG patient and 6 (35%) STG patients underwent surgical ligation (p=0.033). Necrotizing enterocolitis (NEC) with intestinal perforation was the most serious morbidity and occurred in 20% of infants in the ETG, but in no STG infant (p=0.011). Four of the six infants in the ETG with NEC and intestinal perforation died. The overall mortality rate for all infants studied was 28%. We conclude that in extremely premature infants, use of indomethacin during the first 48 hours of life was associated with a reduced need for PDA ligation, but an increased risk of NEC with intestinal perforation.

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References

  1. Ment LR, Oh W, Ehrendranz RA et al. Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial Pediatrics 1994 93: 543–50

    CAS  PubMed  Google Scholar 

  2. Couser RJ, Ferrara TB, Wright GB et al. Prophylactic indomethacin therapy in the first twenty-four hours of life for the prevention of patent ductus arteriosus in preterm infants treated prophylactic with surfactant in the delivery room J Pediatr 1996 128: 631–7

    Article  CAS  Google Scholar 

  3. Fowlie PW . Intravenous indomethacin for preventing mortality and morbidity in very low birth weight infants Cochrane Database Syst Rev Issue 1 2001 Date of most recent update: 30-5-2000 (Review)

  4. Van Overmeire B, Van de Broek H, Van Laer P, Weyler J, Vanhaesebrouck P . Early versus late indomethacin treatment for patent ductus arteriosus in premature infants with respiratory distress syndrome J Pediatr 2001 138: 205–11

    Article  CAS  Google Scholar 

  5. Young TE, Mangum OB . NEOFAX, A Manual of Drugs used in Neonatal Care Ed 7–11 Raleigh, NC: Acorn Publishing 1994–2000

    Google Scholar 

  6. Su BH, Peng CT, Tsai CH . Echocardiographic flow pattern of patent ductus arteriosus: a guide to indomethacin treatment in premature infants Arch Dis Child Fetal Neonatal Ed 1999 81: F197–200

    Article  CAS  Google Scholar 

  7. Papile LA, Burstein J, Burstein R, Koffler H . Incidence and evolution of the subependymal intraventricular hemorrhage: a study of infants with weights less than 1500 g J Pediatr 1978 92: 529–34

    Article  CAS  Google Scholar 

  8. Patz A . An international classification of retinopathy of prematurity Pediatrics 1984 74: 160–1

    CAS  PubMed  Google Scholar 

  9. Patz A . The international committee for the classification of the late stages of retinopathy of prematurity. An international classification of retinopathy of prematurity: II. The classification of retinal detachment Arch Ophthalmol 1987 105: 906–12 [Erratum: Arch Ophthalmol 1987;105:1498]

    Article  Google Scholar 

  10. Barton L, Siassi B, Acherman R, Ramanatha R . Low dose indomethacin for patent ductus arteriosus in extremely low birth weight infants Pediatr Res 2001 49: (Abstract 194)

  11. Grosfeld JL, Chaet M, Molinari F et al. Increased risk of necrotizing enterocolitis in premature infants with patent ductus arteriosus treated with indomethacin Ann Surg 1996 224: 350–7

    Article  CAS  Google Scholar 

  12. Pezzati M, Vangi V, Biagiotti R, Bertini G, Cianciulli D, Rubaltelli FF . Effects of indomethacin and ibuprofen on mesenteric and renal blood flow in preterm infants with patent ductus arteriosus J Pediatr 1999 135: 733–8

    Article  CAS  Google Scholar 

  13. Vasan S, Gotoff PU . Prevention of neonatal necrotizing enterocolitis Clin Perinatol 1994 21: 425–35

    Article  CAS  Google Scholar 

  14. Lawrence D, Brewer D, Hornung R, Mersmann M, Donovan E . Antenatal glucocorticoid use, not perinatal antibiotics, may result in increased risk of necrotizing enterocolitis (NEC) in very-low-birthweight (VLBW) infants Pediatr Res 2001 49: (Abstract 1798)

  15. Gordon PV, Young ML, Marshall DD . Focal small bowl perforation: an adverse effect of early postnatal dexamethasone therapy in extremely low birth weight infants J Perinatol 2001 21: 156–60

    Article  CAS  Google Scholar 

  16. Gordon PV, Rutledge J, Swain R, Thomas S, Woodrum D . Early postnatal dexamethasone increases risk of focal small bowel perforation in extremely low birth weight infants J Perinatol 1999 19: 573–7

    Article  CAS  Google Scholar 

  17. Garland JS, Alex CP, Pauly TH et al. A three-day course of dexamethasone therapy to prevent chronic lung disease in ventilated neonates: a randomized trial Pediatrics 1999 104: 91–9

    Article  CAS  Google Scholar 

  18. Stark AR, Carlo WA, Tyson JE et al. Adverse effects of early dexamethasone in extremely-low-birth-weight infants N Engl J Med 2001 344: 95–101

    Article  CAS  Google Scholar 

  19. MacKendrick W, Caplan M . Impact of prophylactic Indomethacin usage at &lt;27 weeks' gestation in a single institution Pediatr Res 2001 49: (Abstract 2147)

  20. Schmidt B, Davis P, Moddemann D et al. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants N Engl J Med 2001 44: 1966–72

    Article  Google Scholar 

  21. Goppelt-Stuebe M . Molecular mechanisms involved in the regulation of prostaglandin biosynthesis by glucocorticoids Biochem Pharmacol 1997 53: 1389–95

    Article  Google Scholar 

  22. Momma K, Takao A . Increased constriction of the ductus arteriosus with combined administration of indomethacin and betamethasone in fetal rats Pediatr Res 1989 25: 69–75

    Article  CAS  Google Scholar 

  23. Gersony WM, Peckham GH, Ellison RC, Miettinen OS, Nadas AS . Effects of indomethacin in premature infants with patent ductus arteriosus: results of a national collaborative study J Pediatr 1983 102: 895–905

    Article  CAS  Google Scholar 

  24. Nandgaonkar BN, Rotschild T, Yu K, Higgins RD . Indomethacin improves oxygen-induced retinopathy in the mouse Pediatr Res 1999 46: 184–8

    Article  CAS  Google Scholar 

  25. Hardy P, Dumont I, Bhattacharya M et al. Oxidants, nitric oxide and prostanoids in the developing ocular vasculature: a basis for ischemic retinopathy Cardiovasc Res 2000 47: 489–509

    Article  CAS  Google Scholar 

  26. Ment LR, Vohr B, Allan W et al. Outcome of children in the indomethacin intraventricular hemorrhage prevention trial Pediatrics 2000 105: 485–91

    Article  CAS  Google Scholar 

  27. Dani C, Bertini G, Reali MF et al. Prophylaxis of patent ductus arteriosus with ibuprofen in preterm infants Acta Paediatr 2000 89: 1369–74

    Article  CAS  Google Scholar 

  28. Lago P, Slavadori S, Bettiol T, Pitassi I, Chiandetti L, Saia OS . Effects of indomethacin and ibuprofen on renal function in preterm infants treated for patent ductus arteriosus: a randomized controlled trial Pediatr Res 2001 49: (Abstract 2154)

  29. Van Overmeire B, Smets K, Lecoutere D et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus N Engl J Med 2000 343: 674–81

    Article  CAS  Google Scholar 

  30. Patel J, Roberts I, Azzopardi D, Hamilton P, Edwards AD . Randomized double-blind controlled trial comparing the effects of ibuprofen with indomethacin on cerebral hemodynamics in preterm infants with patent ductus arteriosus Pediatr Res 2000 47: 36–46

    Article  CAS  Google Scholar 

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Fujii, A., Brown, E., Mirochnick, M. et al. Neonatal Necrotizing Enterocolitis With Intestinal Perforation in Extremely Premature Infants Receiving Early Indomethacin Treatment for Patent Ductus Arteriosus. J Perinatol 22, 535–540 (2002). https://doi.org/10.1038/sj.jp.7210795

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