Use of nonaspirin nonsteroidal anti-inflammatory drugs during pregnancy and the risk of spontaneous abortion

Background: The association between the use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy and the risk of spontaneous abortion remains unclear because of inconsistent research results and the lack of evidence for an effect due to specific types or dosages of nonaspirin NSAIDs. We aimed to quantify the association between having a spontaneous abortion and types and dosages of nonaspirin NSAIDs in a cohort of pregnant women.

Methods: Using a nested case–control design, we obtained data from the Quebec Pregnancy Registry for 4705 women who had a spontaneous abortion. For each instance, we randomly selected 10 controls from the remaining women in the registry who were matched by index date (date of the spontaneous abortion) and gestational age. Use of nonaspirin NSAIDs (identified by filled prescriptions) and nonuse were compared. We also looked for associations between different types and dosages of nonaspirin NSAIDs and having a spontaneous abortion. Analyses of associations and adjustment for confounding were done using conditional logistic regression.

Results: We identified 4705 cases of spontaneous abortion (352 exposed [7.5%]); 47 050 controls (1213 exposed [2.6%]). Adjusting for potential confounders, the use of nonaspirin NSAIDs during pregnancy was significantly associated with the risk of spontaneous abortion (odds ratio [OR] 2.43, 95% confidence interval [CI] 2.12–2.79). Specifically, use of diclofenac (OR 3.09, 95% CI 1.96–4.87), naproxen (OR 2.64, 95% CI 2.13–3.28), celecoxib (OR 2.21, 95% CI 1.42–3.45), ibuprofen (OR 2.19, 95% CI 1.61–2.96) and rofecoxib (OR 1.83, 95% CI 1.24–2.70) alone, and combinations thereof (OR 2.64, 95% CI 1.59–4.39), were all associated with increased risk of spontaneous abortion. No dose–response effect was seen.

Interpretation: Gestational exposure to any type or dosage of nonaspirin NSAIDs may increase the risk of spontaneous abortion. These drugs should be used with caution during pregnancy