Researchers say health records of 50,000 women link over-the-counter anti-inflammatories and deaths of fetuses.

Use of common anti-inflammatory drugs such as ibuprofen and naproxen if taken early in pregnancy may increase the chance of miscarriage, a new study suggests.


Risk of miscarriage more than doubled in women who took non-steroidal anti-inflammatory drugs, or NSAIDs, during the first 20 weeks of gestation, according to researchers who scrutinized health records from nearly 50,000 Canadian women.

The study appears in the latest issue of the Canadian Medical Association Journal.

“I would strongly suggest that women take no non-steroidal anti-inflammatory drugs during the first trimester,” said study co-author Anick Berard, a professor of epidemiology at the University of Montreal and director of the research unit on medications and pregnancy at Centre Hospitalier Universitaire Ste. Justine. “If a woman is taking an NSAID for a chornic condition she really has to talk to her health care provider to see if it’s feasible to stop at least during the first trimester.”

Use of NSAIDs is fairly common, Berard noted, adding that studies have shown that up to 17 percent of pregnant women take the drugs, either in prescription or over-the-counter formulations. The new study investigated use of non-aspirin NSAIDs such as ibuprofen, naproxen and other drugs.

However, a leading expert in maternal fetal medicine cautioned women not to overreact to the new findings. The increased risk could be due to something else that women who took NSAIDS had in common, said Dr. Hyagriv Simhan, associate professor and chief of the division of maternal-fetal medicine at the University of Pittsburgh Medical Center and medical director of obstetrical services at Magee-Womens Hospital of UPMC.

Don’t overreact, expert says
“I wouldn’t want this to be a reason for women who have taken a Motrin before they realized they were pregnant to freak out,” Simhan said.

Beyond this, Simhan said, there are legitimate reasons for women to be taking NSAIDS. “This study wouldn’t necessarily make me change the way I practice,” he added.

The Canadian study compared the medical records of 4,705 women who had a miscarriage during the first 20 weeks of gestation with records of 47,050 women who became pregnant and delivered a child. The women in the study were aged 15 to 45 when they became pregnant.

Berard and her colleagues considered a woman to have been exposed to an NSAID if she had a prescription for the drug filled before she became pregnant or during early pregnancy. Most NSAIDs in Canada are available through prescription rather than over-the-counter, the authors said.

Among women who had miscarriages, 352 had taken NSAIDs, compared with 1,213 of the women who did not experience pregnancy loss.

When calculating the risk associated with NSAID use, the researchers accounted for other factors that might increase the likelihood of miscarriage, such as diabetes, high blood pressure, heart disease, asthma, lupus, rheumatoid arthritis, depression and anxiety.

Taking all those factors into account, Berard and her colleagues determined that women who took prescription NSAIDs early in pregnancy were 2.4 times as likely to have a miscarriage as those who did not. The rate of miscarriage in women who took NSAIDs was about 35 percent, compared with the normal rate of miscarriage, which is about 15 percent.

While the study didn’t address the kind of over-the-counter use of NSAIDs found in the U.S., the authors cautioned against any use of the drugs in early pregnancy.

“Gestational exposure to any type or dosage of non-aspirin NSAIDs may increase risk of spontaneous abortion. These drugs should be used with caution during pregnancy,” the authors concluded.

NSAIDs may affect prostaglandin levels
The researchers hypothesize that NSAIDs could have an impact on pregnancy because the drugs affect the levels of hormone-like substances known as prostaglandins. Normally in pregnancy, prostaglandins decrease in the uterus in a consistent way, Berard said. It’s possible that NSAIDs cause these levels to fluctuate, she suggested.

One thing Berard and her colleagues don’t know was why the women were given prescriptions for NSAIDs. That’s an important factor, Simhan said. It’s always possible that some of the women who miscarried were taking the medications for cramping which is a sign of impending pregnancy loss, he added.

Berard doesn’t believe this is the case. Women who had miscarriages generally didn’t get more prescriptions for NSAIDs in the two weeks leading up to their pregnancy losses, she explained.

Previous studies about the impact of NSAIDs in early pregnancy had shown mixed results, Berard said.

Nevertheless, she does allow that this kind of study can’t prove that NSAIDs actually cause pregnancy loss.

“We cannot say for 100 percent sure that this is a true drug effect,” she said. “But we’re one step closer to proving causality when there is repetition of the finding. And there is at least one other study looking at this specifically that found an increased risk.”

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