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Centre for Evidence-
Based Medicine

Premature infants: Prophylactic intravenous indomethacin decreases risk of PDA

Clinical Bottom Line

All trials suggest that prophylactic indomethacin is associated with short-term benefits, namely reduction of Patent Ductus Arteriosus (PDA) and severe Intraventricular Hemorrhage (IVH grade 3 and 4).


Fowlie PW. Prophylactic intravenous indomethacin in very low birth weight infants (Cochrane Review). In: The Cochrane Library, 1997. Oxford: Update Software.
Lead author's name and fax: Fowlie PW. Fax: 01382 645783

Clinical Question

In a very premature infant, does indomethacin prophylaxis improve survival without severe disability?

Search Terms

"Indomethacin" in the NIH Web Site that publishes all neonatal reviews for the Cochrane Collaboration: silk.nih.gov/silk/cochrane (no longer online).

The Review

  • Data Sources: Medline, Embase, Oxford Database of Perinatal Trials
  • Study Selection: Restricted to randomised controlled trials using prophylactic intravenous indomethacin in newborn infants with birth weights <1751 grams.
  • Data Extraction: Each of the articles identified by the original literature search was assessed independently, using the inclusion criteria, by the author and a colleague trained in research methodology. Each selected article was reviewed by the author and the outcomes measured were recorded, initially without specific data. Any discrepancies were resolved by a third data extraction. The data from abstracts were compared with those from full manuscripts by the same author(s) to avoid duplicating data.
  • Multiple independent reviews of individual reports? No
  • Tested for heterogeneity? No

The Evidence

Outcome Time to Outcome Typical CER Typical OR RRR NNT p Value
All intraventricular hemorrhage (IVH) 0.3599 0.61 29% 10
95% Confidence Intervals 0.47 to 0.79 7 to 19
For IVH Grade 3 and 4 0.1336 0.55 41% 18
95% Confidence Intervals 0.37 to 0.80 13 to 42
For symptomatic PDA 0.3293 0.29 62% 5
95% Confidence Intervals 0.21 to 0.40 4 to 6


Despite the evidence of short-term benefits, indomethacin prophylaxis is not widely used in many countries, due to concerns about drug safety (e.g. the risk of necrotizing enterocolitis and gastro-intestinal perforations) and the lack of convincing data on long-term outcomes after indomethacin prophylaxis in this high-risk population. Therefore, an international placebo-controlled trial was launched in 1996, to determine whether the prophylactic administration of low-dose indomethacin to infants weighing 500-999 grams at birth improves survival without neurosensory impairment to a corrected age of 18 months. This trial is funded by the Medical Research Council of Canada, and co-sponsored by the National Institute of Child Health and Human Development. Twelve-hundred and two infants have been enrolled between 1996 and 1998 in Canada, the US, Australia, New Zealand and Hong Kong. Follow-up will be completed early in the year 2000. For further information, please contact Barbara Schmidt.

Appraised By

Barbara Schmidt, MD, MSc, FRCP(C), and Bo Zhang, MPH
HSC 3N11E, Department of Pediatrics and Clinical Epidemiology & Biostatistics
McMaster University
1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5

Fax: (905) 521-5007
Friday, February 25, 1999
Email: schmidt@fhs.mcmaster.ca, zhangbo@fhs.mcmaster.ca

Expiry Date

Kill or Update By: December 31, 2000