Popular painkillers linked to miscarriage.

Women trying to get pregnant or who are in the early stages of pregnancy should avoid taking certain painkillers, a new study suggests. Researchers in California report that women who took aspirin, ibuprofen, or related pain-fighting medications around the time of conception or in the early weeks of pregnancy were more likely to have a miscarriage than others were.

Scientists from the Kaiser Foundation Research Institute in Oakland, Calif., interviewed 1,055 women soon after they got positive results from pregnancy tests at a health-care clinic. Each woman in the study group was planning to continue her pregnancy and attend the clinic for prenatal care.

Aspirin, ibuprofen, and naproxen belong to a class of medications called nonsteroidal anti-inflammatory drugs, or NSAIDs (pronounced en-saids). Just 53 women in the study said they had used NSAIDs other than aspirin around the time of conception or early in their pregnancy. Of these women, 13 had miscarriages--a rate that's 80 percent higher than that among the 762 women who had taken no drugs.

Overall, the 22 women taking just aspirin around the time of conception or early in pregnancy were 60 percent more likely to have a miscarriage than were women who didn't take painkillers. However, the 172 women who took the popular pain medication acetaminophen had no increased risk of miscarriage.

Researcher De-Kun Li of Kaiser says that the "striking contrast" between the effect of acetaminophen and that of NSAIDs strengthens the results.

"Our findings show the highest risk at conception," says Li.

In their report in the Aug. 16 British Medical Journal, the researchers explain that they adjusted for some other risk factors in their data analysis, including previous miscarriages, maternal age, and whether the women had smoked, used a hot tub, or consumed alcohol since their last menstrual period.

The study follows up on a study at the University of Aarhus in Denmark in 2001 in which researchers examined patients' medical records and the national birth registry. The team found an association between miscarriages after 28 weeks and NSAID usage in the weeks immediately before the miscarriage.

NSAIDs alleviate pain by suppressing the production of prostaglandins in the entire body. Prostaglandins are fatty acids that have a range of hormonelike effects, for example, controlling blood clotting and smooth-muscle contraction. The uterine lining synthesizes prostaglandins around the time of embryo implantation. "Inhibiting the prostaglandins can interrupt the normal process of implantation," Li says.

Sudhansu Dey, who studies embryo implantation at Vanderbilt University in Nashville, says the new results make sense. In a 2001 study, he found that NSAIDs interfere with embryo implantation and pregnancy in mice. "This all needs to be investigated very carefully;' he says. "Indiscriminate use of NSAIDs can cause a lot of problems during pregnancy"

However, Nick Henderson, director general of the International Ibuprofen Foundation in Marlborough, England, calls the study "alarmist." Claiming an overall increased miscarriage risk of 80 percent on the basis of the pregnancy outcomes of so few women is "overstating the significance of the data," he says. Drug companies make up the foundation's membership.

Melanie Davies of the Royal College of Obstetricians and Gynecologists in London issued a statement reminding women of the small size of the study and recommending that they consult their doctors if they have concerns about taking painkillers.

Li concedes that the findings need to be replicated to establish a firm link between NSAIDs and miscarriage. "Generally, women are advised to avoid unnecessary medication during pregnancy anyway," he says.