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Indomethacin Prohylaxis in VLBW Infants Does Not Reduce Mortality or Survival Without Neurosensory Impairment

Question

  • Indomethacin prophylaxis reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage in very-low-birth-weight infants. Does it confer any long term benefits that outweigh the risks of treatment?

Clinical Bottom Lines

  1. In extremely-low-birth-weight infants (< 1000g), the prophylactic administration of indomethacin does not reduce mortality or improve the rate of survival without neurosensory impairment (cerebral palsy, cognitive delay, hearing loss requiring amplification, and bilateral blindness) at 18 months of age.
  2. Indomethacin prophylaxis does reduce the frequency of patent ductus arteriosus, the need for further medical treatment of patent ductus arteriosus, and the need for surgical ligation of patent ductus arteriosus.
  3. The prophylactic administration of indomethacin reduces the frequency of severe periventricular and intraventricular hemorrhage (Grade 3 and 4).
  4. No other outcomes were altered by the prophylactic administration of indomethacin.
  5. Indomethacin prophylaxis did not increase the rates of overt bleeding, oliguria, or necrotizing entercolitis in the study participants.


Summary of Key Evidence

  1. Of the 574 infants with data on primary outcome measures (death, cerebral palsy, cognitive delay, hearing loss requiring amplification, and bilateral blindness) who were assigned to the indomethacin prophylaxis group, 271 (47%) died or survived with impairments compared to the 261 of the 569 infants (46%) assigned to the placebo group (OR 1.1, 95% CI 0.8-1.4, P=0.61).1
  2. Indomethacin prophylaxis reduced the incidence of patent ductus arteriosus (24% vs. 50% in the placebo group; OR 0.3; P<0.001, NNT=4), the need for medical treatment of patent ductus arteriosus (17% vs. 46% in the placebo group; OR 0.2; P<0.001, NNT=3), and the need for surgical ligation of patent ductus arteriosus (7% vs 12% in the placebo group; OR 0.5; P=0.001, NNT=20).
  3. Indomethacin prophylaxis reduced the frequency of severe periventricular and intraventricular hemorrhage (9% vs. 13% in the placebo group; OR 0.7; P=0.02, NNT=25).

Additional Comments

  • Indomethacin may prevent intraventricular hemorrhage by its effect on cerebral perfusion.
  • However, fluctuations in cerebral blood flow may increase the risk of brain ischemia.

Citation

  1. 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 1966-72.
  2. Fowlie PW. Intravenous indomethacin for preventing mortality and morbidity in very low birth weight infants. Cochrane Database of Systematic Reviews, 2000.

CAT Author: Paola Fliman, MD

CAT Appraisers: Alex Kemper, MD

Date appraised: January 21, 2002

Last updated February 25, 2003
Department of Pediatrics and Communicable Diseases
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