NSAIDs in Early Pregnancy Linked to Risk for Miscarriage

Laurie Barclay, MD

September 06, 2011

September 6, 2011 — Use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) in early pregnancy is linked to twice the risk for miscarriage, according to the results of a nested case-control study reported online September 6 in the Canadian Medical Association Journal.

"The association between the use of ...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," write Hamid Reza Nakhai-Pour, MD, PhD, from the University of Montreal and CHU Ste-Justine in Quebec, Canada, and colleagues. "We aimed to quantify the association between having a spontaneous abortion and types and dosages of nonaspirin NSAIDs in a cohort of pregnant women."

Case patients consisted of 4705 women who were identified from the Quebec Pregnancy Registry and who had a spontaneous abortion. For each case patient, the investigators randomly selected 10 control participants from other women in the registry, matching by index date, defined as the date of the spontaneous abortion, and by gestational age. Case patients and control participants were compared in use of nonaspirin NSAIDs, as reflected in filled prescriptions. The investigators analyzed associations between different types and dosages of nonaspirin NSAIDs and spontaneous abortion using conditional logistic regression, with adjustment for confounding variables.

Of the 4705 patients with spontaneous abortion, 352 (7.5%) had NSAID exposure, as did 1213 (2.6%) of 47,050 control participants. The use of nonaspirin NSAIDs during pregnancy was significantly associated with the risk for spontaneous abortion, after adjustment for potential confounders. There was no apparent dose-response effect.

The odds ratio (OR) for spontaneous abortion was 2.43 with any NSAID (95% confidence interval [CI], 2.12 - 2.79), 3.09 with diclofenac (95% CI, 1.96 - 4.87), 2.64 with naproxen (OR, 95% CI, 2.13 - 3.28), 2.21 with celecoxib (95% CI, 1.42 - 3.45), 2.19 with ibuprofen (95% CI, 1.61 - 2.96), 1.83 with rofecoxib (95% CI, 1.24 - 2.70) alone, and 2.64 for combinations of these NSAIDs (95% CI, 1.59 - 4.39).

"Gestational exposure to any type or dosage of nonaspirin NSAIDs may increase the risk of spontaneous abortion," the study authors write.

Limitations of this study include the lack of data on exposure to over-the-counter formulations of nonaspirin NSAIDs during pregnancy, and lack of information on the indications for which nonaspirin NSAIDs were used and on covariables such as smoking and body mass index. In addition, the investigators could not exclude the possibility of chance findings for 5.0% of the statistically significant associations because of the number of comparisons, and the study population covered only 36% of pregnant women in Quebec.

"Given that the use of nonaspirin NSAIDs during early pregnancy has been shown to increase the risk of major congenital malformations and that our results suggest a class effect on the risk of clinically detected spontaneous abortion, nonaspirin NSAIDs should be used with caution during pregnancy," the study authors conclude. "Future research should focus on determining exact mechanisms of action."

The Fonds de la recherche en santé du Québec and the Réseau Québécois de recherche sur l'usage des médicaments supported this study. The study authors have disclosed no relevant financial relationships.

CMAJ. Published online September 6, 2011.

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