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A new Israeli study suggests that general anti-inflammatory drugs, such as ibuprofen, do not increase the risk of miscarriage – but previous Canadian research has shown that exposure to non-steroidal anti-inflammatory drugs (NSAIDs) more than doubles the risk of spontaneous abortion in early pregnancy.

NSAIDs include ibuprofen (Advil and Motrin) as well as prescription anti-inflammatory drugs such as naproxen and diclofenac. Used to reduce pain or fever, they are among the most widely used drugs in pregnancy.

The Israeli study, published Monday in the Canadian Medical Association Journal, looked at data on 65,457 pregnant women aged 15 to 45 years admitted to Soroka Medical Center in Beersheba, Israel, between January, 2003, and December, 2009. The researchers found that pregnant women who took NSAIDs had roughly the same miscarriage rate (about 10 per cent) as women who did not take NSAIDs.

But Dr. Anick Bérard, a professor of epidemiology at the University of Montreal, cautioned against drawing conclusions about the safety of NSAIDs based on the Israeli study. The data in the study were based on self-reporting by women, who may not have remembered which medications they were taking in early pregnancy, Bérard said. She added that women are more likely to take NSAIDs before they know they are pregnant. The researchers did not account for exposure to the drugs before a positive pregnancy test, which could result in misleading findings, Bérard said.

"They are underestimating the exposure to NSAIDs," she said.

Previous studies have shown a link between NSAID exposure and miscarriage.

In 2003, the BMJ published a study by the Kaiser Permanente Medical Care Program in the San Francisco area, showing an 80-per-cent increased risk of miscarriage associated with prenatal NSAID use.

Bérard's own study of NSAIDs, published in the CMAJ in 2011, analyzed the health records of nearly 50,000 Quebec women to study the effects of prescription NSAIDs on pregnancy. Bérard and co-authors found that 35 per cent of women who took NSAIDs suffered a miscarriage, compared with the normal rate of miscarriage of about 15 per cent.

There is a biological explanation for why NSAIDs may cause miscarriage, Bérard said. NSAIDs affect hormone-like substances called prostaglandins. They drugs may interfere with the normal prostaglandin changes that happen in early pregnancy, leading to miscarriage, she explained.

Nevertheless, researchers note it is difficult to prove a cause-and-effect relationship between NSAIDs and miscarriage, since women in need of prescription NSAIDs may have pre-existing conditions that increase their chances of miscarriage.

Bérard's study accounted for factors such as diabetes, high blood pressure, heart disease, asthma, lupus, rheumatoid arthritis, depression and anxiety.

The authors of the Israeli study suggest they went a step further by factoring in conditions such as hyper-coagulation diseases, abnormalities in the uterine structure, polycystic ovary syndrome, obesity and in-vitro fertilization. "Previous studies accounted for only some of those factors, which may explain the increased risk for miscarriages that was found," wrote Dr. Sharon Daniel and Prof. Amalia Levy of Israel's Ben-Gurion University of the Negev and Soroka Medical Center in an e-mail.

Bérard pointed out that genetic predispositions also affect birth outcomes, including miscarriage. The findings of the Israeli study may not be applicable to the Canadian or North American population for this reason alone, she said. Because of the risk of miscarriage, "women should try to avoid using NSAIDs in the first trimester of pregnancy," she said.

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