Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Indomethacin prophylaxis or expectant treatment of patent ductus arteriosus in extremely low birth weight infants?

Journal of Perinatology volume 27, pages 158–163 (2007)Cite this article

Abstract

Background:

Indomethacin prophylaxis or expectant treatment are common strategies for the prevention or management of symptomatic patent ductus arteriosus (sPDA).

Objective:

To compare the clinical responses of extremely low birth weight (ELBW) infants to indomethacin prophylaxis with hat of other infants who were managed expectantly by being treated with indomethacin or surgically only after an sPDA was detected.

Methods:

Retrospective cohort investigation of 167 ELBW infants who received indomethacin prophylaxis (study) and 167 ELBW infants (control) treated expectantly who were matched by year of birth (1999 to 2006), birth weight, gestational age (GA) and gender.

Results:

Mothers of the two groups of infants were comparable demographically and on the history of preterm labor, pre-eclampsia, antepartum steroids and cesarean delivery. Study and control infants were similar in birth weight, GA, low 5 min Apgar scores, surfactant administration, the need for arterial blood pressure control, bronchopulmonary dysplasia and neonatal mortality. Necrotizing enterocolitis, spontaneous intestinal perforations, intraventricular hemorrhage grade III to IV, periventricular leukomalacia and stage 3 to 5 retinopathy of prematurity occurred also with similar frequency in both groups of infants. In the indomethacin prophylaxis group, 29% of the infants developed sPDA, and of them 38% responded to indomethacin treatment. In the expectantly treated group, 37% developed sPDA, and of them 59% responded to indomethacin treatment. Overall, surgical ligation rate for sPDA was similar between both groups of patients.

Conclusion:

In our experience, indomethacin prophylaxis does not show any advantages over expectant early treatment on the management of sPDA in ELBW infants. Although no deleterious effects were observed, prophylaxis exposed a significant number of infants who may have never developed sPDA, to potential indomethacin-related complications.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Hermes-DeSantis ER, Clyman RI . Patent ductus arteriosus: pathophysiology and management. J Perinatol 2006; 26: S14–S18.

    Article  Google Scholar 

  2. Fowlie PW, Davis PG . Prophylactic indomethacin for preterm infants; a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2003; 88: F464–F466.

    Article  CAS  Google Scholar 

  3. Koch J, Hensley G, Roy L, Brown S, Ramaciotti C, Rosenfeld CR . Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less. Pediatrics 2006; 117: 1113–1121.

    Article  Google Scholar 

  4. Clyman RI . Recommendations for the postnatal use of indomethacin: an analysis of four separate treatment strategies. J Pediatr 1996; 128: 601–607.

    Article  CAS  Google Scholar 

  5. Schmidt B, Davis P, Modemann D, Ohlsson A, Roberts RS, Saigal S et al. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med 2001; 344: 1966–1972.

    Article  CAS  Google Scholar 

  6. Darlow BA, Horwood LJ, Clemett S . Retinopathy of prematurity: risk factors in a prospective population-based study. Paediatr Perinat Epidemiol 1992; 6: 62–80.

    Article  CAS  Google Scholar 

  7. Ohlsson A, Bottu J, Govan J, Ryan ML, Fong K, Myhr T . Effect of indomethacin on cerebral blood flow velocities in very low birth weight neonates with a patent ductus arteriosus. Dev Pharmacol Ther 1993; 20: 100–106.

    Article  CAS  Google Scholar 

  8. O'Donovan DJ, Baetiong A, Adams K, Chen A, O'Brien Smith E, Adams JM et al. Necrotizing enterocolitis and gastrointestinal complications after indomethacin therapy and surgical ligation in premature infants with patent ductus arteriosus. J Perinatol 2003; 28: 286–290.

    Article  Google Scholar 

  9. Attridge JT, Clark R, Walker MW, Gordon PV . New insights into spontaneous intestinal perforation using a national data set: (1) SIP is associated with early indomethacin exposure. J Perinatol 2006; 26: 93–99.

    Article  CAS  Google Scholar 

  10. Iams JD, Creasy RK . Preterm labor and delivery In: Creasy RJ, Resnik R, Iams JD (eds). Maternal–Fetal Medicine: Principles and Practice. 5th ed. Saunders; Philadelphia, PA, 2004 pp. 623–651.

    Google Scholar 

  11. 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: 529–534.

    Article  CAS  Google Scholar 

  12. Narayanan M, Cooper B, Weiss H, Clyman RI . Prophylactic indomethacin: factors determining permanent ductus arteriosus closure. J Pediatr 2000; 136: 330–337.

    Article  CAS  Google Scholar 

  13. Norton M, Merrill J, Cooper B, Kuller J, Clyman R . Neonatal complications after the administration of indomethacin for preterm labor. N Engl J Med 1993; 329: 1602–1607.

    Article  CAS  Google Scholar 

  14. Clyman RI, Chen YQ, Chemtob S, Mauray F, Kohl T, Varma DR et al. In utero remodeling of the fetal lamb ductus arteriosus: the role of antenatal indomethacin and a vascular zone thickness on vasa basorum proliferation, neointima formation, and cell death. Circulation 2001; 103: 1806–1812.

    Article  CAS  Google Scholar 

  15. Cordero L, Nankervis CA, Gardner D, Giannone PJ . The effects of indomethacin tocolysis on the postnatal response of the ductus arteriosus to indomethacin in extremely low birth weight infants. J Perinatol 2007; 27: 22–27.

    Article  CAS  Google Scholar 

  16. Van Den Veyver IB, Moise KJ, Ou C, Carpenter RJ . The effect of gestational age and fetal indomethacin levels on the incidence of constriction with advancing gestational age. Am J Obstet Gynecol 1997; 177: 256–261.

    Article  Google Scholar 

  17. Weiss H, Cooper B, Brook M, Schlueter M, Clyman R . Factors determining reopening of the ductus arteriosus after successful clinical closure with indomethacin. J Pediatr 1995; 127: 466–471.

    Article  CAS  Google Scholar 

  18. Clyman RI, Chan CY, Mauray F, Chen YQ, Cox W, Seidner SR et al. Permanent anatomic closure of the ductus arteriosus in newborn baboons: the roles of postnatal constriction, hypoxia and gestation. Pediatr Res 1999; 45: 19–29.

    Article  CAS  Google Scholar 

  19. Trus T, Winthrop AL, Pipe S, Shah J, Langer JC, Lau GYP . Optimal management of patent ductus arteriosus in the neonate weighing less than 800 g. J Pediatr Surg 1993; 28: 1137–1139.

    Article  CAS  Google Scholar 

  20. Fujii AM, Brown E, Mirochnick M, O'Brien S, Kaufman G . Neonatal necrotizing enterocolitis with intestinal perforation in extremely premature infants receiving early indomethacin treatment for patient ductus arteriosus. J Perinatol 2002; 22: 535–540.

    Article  Google Scholar 

  21. Schmidt B, Asztalos EV, Roberts RS, Robertson DM, Suave RS, Whitfield MF . Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months. JAMA 2003; 289: 1124–1129.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Neonatal-Perinatal Medicine, Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH, USA

    L Cordero, C A Nankervis & P J Giannone

  2. Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA

    D DeLooze

Authors
  1. L Cordero
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C A Nankervis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D DeLooze
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P J Giannone
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L Cordero.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cordero, L., Nankervis, C., DeLooze, D. et al. Indomethacin prophylaxis or expectant treatment of patent ductus arteriosus in extremely low birth weight infants?. J Perinatol 27, 158–163 (2007). https://doi.org/10.1038/sj.jp.7211659

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jp.7211659

Keywords

This article is cited by

Search

Advanced search

Quick links