NSAIDs Not Associated with Increased Miscarriage Risk

A study found no significant association between use of nonsteroidal anti-inflammatory drugs by pregnant women and miscarriage, but its authors noted the need for further research.

Taking nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy does not appear to increase the risk of miscarriage, according to a new study conducted in Israel.

Although many women take NSAIDs during pregnancy, studies on the risk of spontaneous abortion associated with their use have produced inconsistent results. To help determine the actual relationship between NSAID use and miscarriage, the researchers of the new study, published online on February 3, 2014, in the Canadian Medical Association Journal, studied a large cohort of women who became pregnant between January 2003 and December 2009.

The historical cohort study included women aged 15 to 45 years who gave birth or had a spontaneous abortion at Soroka Medical Center in Israel. Using a database containing information on medication dispensation and 2 databases of medical records for births and miscarriages, the risks associated with NSAID use were analyzed. NSAIDs were categorized as non-selective cyclooxygenase (COX) inhibitors or COX-2 selective inhibitors. Women were considered to have been exposed to NSAIDs if they were dispensed an NSAID between the first day of their last menstrual period and the day before they were hospitalized for miscarriage or at 20 weeks gestation if the pregnancy ended in birth. The analysis considered additional factors that affect spontaneous abortion including the woman’s age and whether she had diabetes or hypothyroidism or was obese.

The results indicated that NSAID exposure is not an independent risk factor for miscarriage. Of the 65,457 women included in the study, 4495 (6.9%) were exposed to NSAIDs during pregnancy. Among women who took non-selective COX inhibitors, 8.2% experienced spontaneous abortions, compared with 10% of women who took no NSAIDs. Among women who were exposed to selective COX-2 inhibitors, 16.9% miscarried. Although the increased risk of miscarriage associated with exposure to selective COX-2 inhibitors was significant in primary analyses, it was not significant in multivariate analyses. In addition, the researchers found no dose-response relationship between NSAID exposure and miscarriage risk.

When the risks associated with specific NSAIDs were analyzed separately, only indomethacin was associated with a significant increased risk for spontaneous abortion; 12.9% of women in the study who took indomethacin experienced miscarriages. However, indomethacin is often used to treat preterm birth, the researchers note, suggesting that the drug did not cause the miscarriages. When women who were exposed to indomethacin during the 4 days before their miscarriage were eliminated from the analysis, there was no association between use of the drug and miscarriage risk.

The authors conclude that, for the most part, NSAIDs were not found to increase the risk for miscarriage. However, considering the study’s small sample size of women exposed to selective COX-2 inhibitors, the authors suggest that more research is needed to assess the association between these medications and the risk for spontaneous abortion.