Women who use common painkillers like ibuprofen and naproxen early in pregnancy may have an increased risk of miscarriage, a study published Tuesday suggests.

Researchers found that of nearly 52,000 Quebec women who had been pregnant, those who’d used a non-steroidal anti-inflammatory drug (NSAID) after conceiving were more than twice as likely to suffer a miscarriage.

The researchers looked at NSAIDs other than aspirin - which includes such common drugs as ibuprofen (brands like Advil and Motrin), naproxen (Aleve, Naprosyn) and the arthritis drug celecoxib (Celebrex).

They found that of 4,705 women who’d had a miscarriage, 7.5 percent had filled a prescription for an NSAID at some point during pregnancy. That compared with less than three percent of the 47,000 women who had not suffered a miscarriage.

Overall, NSAID use was tied to a 2.4-times higher risk of miscarriage.

In Quebec, ibuprofen is the only non-aspirin NSAID available over-the-counter. And people there commonly get a prescription for it anyway, to have its cost paid by health insurance.

So the findings suggest that both prescription and over-the-counter NSAIDs may be linked to miscarriage, according to senior researcher Anick Berard, of the University of Montreal’s CHU Sainte-Justine Research Center.

The study, reported in the Canadian Medical Association Journal, does not prove that NSAIDs themselves caused some women’s miscarriages.

“I cannot say, 100 percent, that this is cause-and-effect,” Berard said in an interview. “But this could very well be a pharmacological effect.”

Some past research, though not all, has also linked NSAIDs to a higher miscarriage risk.

And Berard said the link seen in this study held up even after the researchers accounted for a number of other factors that might explain it - including underlying medical conditions like rheumatoid arthritis (RA) and lupus, and the women’s use of other medications.

The idea is also plausible from the standpoint of biology, according to Berard.

Levels of hormone-like substances called prostaglandins decline in the uterus during early pregnancy and NSAIDs are known to affect prostaglandin production. The theory is that NSAIDs might affect miscarriage risk by interfering with the normal prostaglandin changes that occur early in pregnancy.

In general, pregnant women are already advised to avoid using any medication, if possible.

Berard said her advice to women who are using NSAIDs for a chronic condition like RA or lupus is to talk with their doctors. They may be able to go off the medications, especially since those diseases often improve during pregnancy.

For women who feel they need a painkiller for a short-term problem, like a headache, acetaminophen (Tylenol) is considered the safest choice, Berard said.

That advice, according to the researcher, also goes for women who are planning a pregnancy, since miscarriages so often occur before a woman even knows she is pregnant.

In general, Berard said, pregnant women have a 15 percent chance of a “clinically detected” miscarriage - one that occurs after a woman knows she is pregnant.

But it’s estimated that up to half of all fertilized eggs are miscarried, usually in the first seven weeks of pregnancy.

SOURCE: CMAJ, online September 6, 2011.