NSAID Use Linked to Miscarriage
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The risk of spontaneous abortion more than doubled (OR 2.43) in women who used any nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy, Canadian investigators found. Analysis by type of NSAID showed that women who took diclofenac had the highest odds ratio for spontaneous abortion (OR 3.09, 95% CI 1.96 to 4.87), whereas users of rofecoxib had the lowest risk (OR 1.83, 95% CI 1.24 to 2.70), Anick Bérard, PhD, of the University of Montreal, and co-authors reported online in CMAJ. The authors found no association between spontaneous abortion and NSAID dosage. "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," they wrote in conclusion. An estimated 17% of women use nonaspirin NSAIDs during pregnancy, despite persisting controversy surrounding gestational use of the drugs. The strongest evidence of potential harm has come from studies of NSAID use around the time of conception, suggesting women took the drugs to alleviate cramping, which often precedes miscarriage, the authors wrote in their introduction. No studies to date had examined the association between NSAIDs and miscarriage according to drug and dosage. Bérard and co-authors sought to address that gap in the data by reviewing NSAID use in a large cohort of pregnant women. The investigators analyzed records in the Quebec Pregnancy Registry, which has accumulated data on all pregnancies in Quebec since 1997. The registry is linked to several administrative databases, including one that contains prospectively collected information on medical services provided, prescriptions, physician diagnoses, and other aspects of patient care. The analysis included all women ages 15 to 45 on the first day of gestation and who had continuous coverage by the provincial drug plan during pregnancy for at least 12 months beforehand. Women who had planned abortions, had spontaneous abortion before 20 weeks of gestation, or who had exposure to known teratogens before 20 weeks' gestation were excluded from the study. NSAID exposure was defined as at least one filled prescription after the start of pregnancy or a prescription filled before pregnancy and overlapping with pregnancy. Each patient with a spontaneous abortion was matched with 10 women who did not miscarry during pregnancy. Of 67,160 initially included in the analysis, 4,705 had spontaneous abortions and were matched with a control group of 47,050 women. Almost three times as many women who miscarried had at least one prescription for nonaspirin NSAIDs during pregnancy as compared with the control group (7.5% versus 2.6%, P<0.05). Spontaneous abortion was associated with older age, residence in urban areas, reliance of social assistance, a higher comorbidity burden, increased use of healthcare resources in the year before pregnancy, fewer prenatal visits, and increased medication use. Naproxen was the most commonly used NSAID, among both the women who miscarried and those who did not (2.8% versus 0.9%), followed by ibuprofen (1.3% versus 0.6%), rofecoxib (0.8% versus 0.3%), diclofenac (0.7% versus 0.2%), and celecoxib (Celebrex, 0.6% versus 0.2%). Women in the study group also were more likely to have prescriptions for two or more NSAIDs (0.6% versus 0.2%). After adjusting for multiple confounders, the investigators found that women who had spontaneous abortions were more than twice as likely to use NSAIDs during pregnancy (OR 2.43, 95% CI 2.12 to 2.79). Limiting NSAID use to the two weeks before spontaneous abortion, the authors found the odds ratio increased to 3.47 (95% CI 2.01 to 6.00). The authors acknowledged several limitations of their findings: lack of data on use of nonprescription NSAIDs, inability to document whether a filled prescription was actually used, lack of information on the indication for NSAIDs, and exclusion of spontaneous abortions that were not clinically detected.
The
study was supported by the Fonds de la recherche en santé dur Quebec
and the Réseau Québécois de recherche sur l'usage des médicaments.
The authors had no relevant disclosures. |
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