Nonsteroidal antiinflammatory drugs during third trimester and the risk of premature closure of the ductus arteriosus: a meta-analysis

Ann Pharmacother. 2006 May;40(5):824-9. doi: 10.1345/aph.1G428. Epub 2006 Apr 25.


Background: Nonsteroidal antiinflammatory drugs (NSAIDs) are increasingly being used during pregnancy to treat a variety of conditions. An evaluation of the risk of premature closure of the ductus arteriosus is useful in determining the safety of NSAIDs at different stages of pregnancy.

Objective: To determine whether NSAID use during the third trimester of pregnancy is associated with an increased risk of premature constriction of the ductus arteriosus.

Methods: A systematic review was conducted of MEDLINE (1966-2004), Embase (1980-2004), and the Cochrane Database of Systematic Reviews (1991-2004). Summary estimates of the odds ratios, comparing ductal outcomes in exposed and unexposed fetuses, and their 95% confidence intervals were calculated assuming a random effects model.

Results: Based on 217 patients exposed to indomethacin and 221 to placebo, the risk of ductal closure was 15-fold higher in the group of women exposed to NSAIDs compared with those receiving either placebo or other NSAIDs (8 studies; OR = 15.04, 95% CI 3.29 to 68.68). There was no significant increased risk of ductal closure in the infants of women treated with indomethacin compared with those receiving other drugs (4 studies; OR = 2.12, 95% CI 0.48 to 9.25). Similar results were found when calculating rate differences.

Conclusions: Short-term use of NSAIDs in late pregnancy is associated with a significant increase in the risk of premature ductal closure.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Abnormalities, Drug-Induced / etiology*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Ductus Arteriosus / abnormalities*
  • Female
  • Humans
  • Indomethacin / adverse effects
  • Pregnancy
  • Pregnancy Trimester, Third
  • Randomized Controlled Trials as Topic
  • Sulindac / adverse effects


  • Anti-Inflammatory Agents, Non-Steroidal
  • Sulindac
  • Indomethacin