NSAID Use Tied to Miscarriage Risk

Taking nonsteroidal anti-inflammatory drugs during pregnancy more than doubled the risk of miscarriage, researchers reported.

Women who take ibuprofen, naproxen, and other nonsteroidal anti-inflammatory drugs while pregnant face more than double the risk of miscarriage, according to a new study published in the September 6 issue of the Canadian Medical Association Journal. The widely reported results—though limited to prescribed NSAIDs—may prompt questions from patients about the safe use of similar OTC products during pregnancy.

“This study shows that NA-NSAIDs use during early pregnancy is associated with a statistically significant 2.4-fold increased risk of having a spontaneous abortion,” wrote lead study author Anick Bérard, PhD, FISPE, an epidemiologist and professor of pharmacy at the University of Montreal and director of the research unit on medications and pregnancy at Québec’s Centre Hospitalier Universitaire Ste. Justine (CHU).

To find out if NSAIDs could induce miscarriage, she and coauthors examined prescription records of 4705 women who miscarried during the first 20 weeks of pregnancy and compared them with the records of 47,050 women who did not miscarry. Exposure to NSAIDs was defined as having filled at least one prescription for diclofenac, naproxen, celecoxib, ibuprofen, or rofecoxib in the first 20 weeks of pregnancy or just prior to becoming pregnant.

Among women who miscarried, 7.5% had filled a prescription for NSAIDs, compared with just 2.6% of those who did not miscarry. Analyzing by type, researchers found that diclofenac carried the highest risk of miscarriage, whereas rofecoxib carried the lowest risk. Dosages did not have a discernible impact on participants’ chances of miscarrying. In their report, the authors wrote that the findings were consistent and suggest a “class effect” with NSAIDs.

Dr. Bérard and her team took the steps needed to ensure that the miscarriages were not symptomatic of an underlying chronic condition, such as diabetes, hypertension, or cardiovascular disease. The epidemiologist told Health Day: “We went through a lot of pain and misery to make sure what we’re seeing is due to the drug and not a consequence of symptoms or risk attributed to rheumatoid arthritis, for example.”

Despite the team’s efforts, however, the study’s limitations meant independent experts were less willing to interpret the findings as conclusive. For example, the researchers had no way to identify whether patients actually used the medications or identify miscarriages that were not clinically detected. Canadian prescribing practices also prevented investigators from reporting on NSAIDs obtained over the counter.

The lack of OTC data is significant when considering the study’s practical applications for US patients, said Hyagriv Simhan, MD, of the University of Pittsburgh Medical Center. “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,” Dr. Simhan told an MSNBC reporter. He added that the study “wouldn’t necessarily make me change the way I practice.”

Dr. Bérard said that although she and her team “cannot be 100 percent sure that this is a true drug effect,” the results warrant a word of caution to all women considering using NSAIDs during the first few months of pregnancy. “I would strongly suggest that women take no NSAIDs during the first trimester,” she concluded.

For other articles in this issue, see:

• Petition Calls for Boxed Warning on PPIs
• FDA Takes on Unsafe Pill Splitting