Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study

BMJ 2003; 327 doi: (Published 14 August 2003) Cite this as: BMJ 2003;327:368
  1. De-Kun Li, epidemiologist (dkl{at},
  2. Liyan Liu, programmer analyst1,
  3. Roxana Odouli, research associate1
  1. 1 Division of Research, Kaiser Foundation Research Institute, Kaiser Permanente, 2000 Broadway, Oakland, California 94612, USA
  1. Correspondence to: D-K Li
  • Accepted 2 June 2003


Objective To evaluate whether prenatal use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of miscarriage.

Design Population based cohort study. Prenatal use of NSAIDs, aspirin, and paracetamol (acetaminophen) ascertained by in-person interview.

Setting Kaiser Permanente Medical Care Program, a healthcare delivery system, in the San Francisco area of the United States.

Participants 1055 pregnant women recruited and interviewed immediately after their positive pregnancy test. Median gestational age at entry to the study was 40 days.

Main outcome measures Pregnancy outcomes up to 20 weeks of gestation.

Results 53 women (5%) reported prenatal NSAID use around conception or during pregnancy. After adjustment for potential confounders, prenatal NSAID use was associated with an 80% increased risk of miscarriage (adjusted hazard ratio 1.8 (95% confidence interval 1.0 to 3.2)). The association was stronger if the initial NSAID use was around the time of conception or if NSAID use lasted more than a week. Prenatal aspirin use was similarly associated with an increased risk of miscarriage. However, prenatal use of paracetamol, pharmacologically different from NSAIDs and aspirin, was not associated with increased risk of miscarriage regardless of timing and duration of use.

Conclusion Prenatal use of NSAIDs and aspirin increased the risk of miscarriage. These findings need confirmation in studies designed specifically to examine the apparent association.


  • Contributors D-KL conceived of and designed the study and analysed and interpreted the data. LL helped analyse and interpret the data. RO helped design the study and collected the data. D-KL is the guarantor of this paper and took full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish.

  • Funding The study was supported in part by funds from the California Public Health Foundation and the National Institute of Child Health and Human Development (NICHD).

  • Competing interests None declared.

  • Ethical approval The Institutional Review Board of Kaiser Permanente approved the protocol and conduct of the study.

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