Skip to main content
PMC home page
Archives of Disease in Childhood. Fetal and Neonatal Edition logoLink to Archives of Disease in Childhood. Fetal and Neonatal Edition
. 2003 Nov;88(6):F464–F466. doi: 10.1136/fn.88.6.F464

Prophylactic indomethacin for preterm infants: a systematic review and meta-analysis

P Fowlie, P Davis
PMCID: PMC1763231  PMID: 14602691

Abstract

Background: Rates of long term morbidity remain unacceptably high in infants surviving after preterm birth. Prophylactic indomethacin has been shown to effectively reduce the rate of intraventricular haemorrhage in this group but there is the potential for unwanted side effects because of reduced organ perfusion.

Objective: To examine the effect of prophylactic indomethacin on mortality and short and long term morbidity of preterm infants.

Data sources: Medline (1966–2002), the Cochrane Controlled Trials Register and abstracts of the Society for Pediatric Research and the European Society for Pediatric Research were searched independently by both authors.

Review methods: Trials were included if they used a randomised design, enrolled preterm infants given intravenous indomethacin within 24 hours of birth, and reported any of the prespecified outcome measures. Each author extracted data and assessed trial quality independently, according to the methods of the Cochrane Collaboration. Data were combined in a meta-analysis where appropriate.

Results: Nineteen trials fulfilling the inclusion criteria were identified, of which four reported long term outcomes. Short term benefits of indomethacin were identified, including a reduction in the rate of severe intraventricular haemorrhage (relative risk (RR) 0.66 (95% confidence interval (CI) 0.53 to 0.82)) and the need for surgical ligation of a patent ductus arteriosus (RR 0.51 (95% CI 0.37 to 0.71)). No evidence of short term gastrointestinal or renal adverse effects was detected. There was no significant difference between indomethacin and control groups with respect to the important long term outcome of death or severe neurosensory impairment (RR 1.02 (95% CI 0.90 to 1.15)).

Conclusions: Prophylactic indomethacin has a number of short term benefits for the preterm infant but there is no evidence to suggest that it results in an improvement in the rate of survival free of disability.

Full Text

The Full Text of this article is available as a PDF (169.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bada H. S., Green R. S., Pourcyrous M., Leffler C. W., Korones S. B., Magill H. L., Arheart K., Fitch C. W., Anderson G. D., Somes G. Indomethacin reduces the risks of severe intraventricular hemorrhage. J Pediatr. 1989 Oct;115(4):631–637. doi: 10.1016/s0022-3476(89)80300-2. [DOI] [PubMed] [Google Scholar]
  2. Bandstra E. S., Montalvo B. M., Goldberg R. N., Pacheco I., Ferrer P. L., Flynn J., Gregorios J. B., Bancalari E. Prophylactic indomethacin for prevention of intraventricular hemorrhage in premature infants. Pediatrics. 1988 Oct;82(4):533–542. [PubMed] [Google Scholar]
  3. Couser R. J., Ferrara T. B., Wright G. B., Cabalka A. K., Schilling C. G., Hoekstra R. E., Payne N. R. Prophylactic indomethacin therapy in the first twenty-four hours of life for the prevention of patent ductus arteriosus in preterm infants treated prophylactically with surfactant in the delivery room. J Pediatr. 1996 May;128(5 Pt 1):631–637. doi: 10.1016/s0022-3476(96)80127-2. [DOI] [PubMed] [Google Scholar]
  4. Fowlie P. W. Prophylactic indomethacin: systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 1996 Mar;74(2):F81–F87. doi: 10.1136/fn.74.2.f81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hanigan W. C., Kennedy G., Roemisch F., Anderson R., Cusack T., Powers W. Administration of indomethacin for the prevention of periventricular-intraventricular hemorrhage in high-risk neonates. J Pediatr. 1988 Jun;112(6):941–947. doi: 10.1016/s0022-3476(88)80224-5. [DOI] [PubMed] [Google Scholar]
  6. Irving C. S., Lifschitz C. H., Wong W. W., Boutton T. W., Nichols B. L., Klein P. D. Characterization of HCO3-/CO2 pool sizes and kinetics in infants. Pediatr Res. 1985 Apr;19(4):358–363. doi: 10.1203/00006450-198519040-00009. [DOI] [PubMed] [Google Scholar]
  7. Krueger E., Mellander M., Bratton D., Cotton R. Prevention of symptomatic patent ductus arteriosus with a single dose of indomethacin. J Pediatr. 1987 Nov;111(5):749–754. doi: 10.1016/s0022-3476(87)80262-7. [DOI] [PubMed] [Google Scholar]
  8. Mahony L., Caldwell R. L., Girod D. A., Hurwitz R. A., Jansen R. D., Lemons J. A., Schreiner R. L. Indomethacin therapy on the first day of life in infants with very low birth weight. J Pediatr. 1985 May;106(5):801–805. doi: 10.1016/s0022-3476(85)80361-9. [DOI] [PubMed] [Google Scholar]
  9. Ment L. R., Duncan C. C., Ehrenkranz R. A., Kleinman C. S., Pitt B. R., Taylor K. J., Scott D. T., Stewart W. B., Gettner P. Randomized indomethacin trial for prevention of intraventricular hemorrhage in very low birth weight infants. J Pediatr. 1985 Dec;107(6):937–943. doi: 10.1016/s0022-3476(85)80197-9. [DOI] [PubMed] [Google Scholar]
  10. Ment L. R., Duncan C. C., Ehrenkranz R. A., Kleinman C. S., Taylor K. J., Scott D. T., Gettner P., Sherwonit E., Williams J. Randomized low-dose indomethacin trial for prevention of intraventricular hemorrhage in very low birth weight neonates. J Pediatr. 1988 Jun;112(6):948–955. doi: 10.1016/s0022-3476(88)80225-7. [DOI] [PubMed] [Google Scholar]
  11. Ment L. R., Oh W., Ehrenkranz R. A., Philip A. G., Vohr B., Allan W., Duncan C. C., Scott D. T., Taylor K. J., Katz K. H. Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial. Pediatrics. 1994 Apr;93(4):543–550. [PubMed] [Google Scholar]
  12. Ment L. R., Oh W., Ehrenkranz R. A., Phillip A. G., Vohr B., Allan W., Makuch R. W., Taylor K. J., Schneider K. C., Katz K. H. Low-dose indomethacin therapy and extension of intraventricular hemorrhage: a multicenter randomized trial. J Pediatr. 1994 Jun;124(6):951–955. doi: 10.1016/s0022-3476(05)83191-9. [DOI] [PubMed] [Google Scholar]
  13. Rennie J. M., Doyle J., Cooke R. W. Early administration of indomethacin to preterm infants. Arch Dis Child. 1986 Mar;61(3):233–238. doi: 10.1136/adc.61.3.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schmidt B., Davis P., Moddemann D., Ohlsson A., Roberts R. S., Saigal S., Solimano A., Vincer M., Wright L. L., Trial of Indomethacin Prophylaxis in Preterms Investigators Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med. 2001 Jun 28;344(26):1966–1972. doi: 10.1056/NEJM200106283442602. [DOI] [PubMed] [Google Scholar]
  15. Supapannachart S., Khowsathit P., Patchakapati B. Indomethacin prophylaxis for patent ductus arteriosus (PDA) in infants with a birth weight of less than 1250 grams. J Med Assoc Thai. 1999 Nov;82 (Suppl 1):S87–S92. [PubMed] [Google Scholar]
  16. Vincer M., Allen A., Evans J., Nwaesei C., Stinson D., Rees E., Fraser A. Early intravenous indomethacin prolongs respiratory support in very low birth weight infants. Acta Paediatr Scand. 1987 Nov;76(6):894–897. doi: 10.1111/j.1651-2227.1987.tb17260.x. [DOI] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood Fetal and Neonatal Edition are provided here courtesy of BMJ Publishing Group

RESOURCES