(This June 20 story corrects source’s affiliation in paragraph 4 to indicate that he is not part of the Kaiser Foundation Research Institute.)

(Reuters Health) - Using non-steroidal anti-inflammatory drugs (NSAIDs) around the time of conception significantly increases the risk of miscarriage in the first eight weeks of pregnancy, a study suggests.

Researchers compared newly pregnant women who used NSAIDs around the time of conception or early in their pregnancy to those who used acetaminophen or no painkillers, and found using NSAIDs around conception carried a more than four-fold higher risk of early miscarriage.

The results support earlier evidence that NSAIDs interfere with prostaglandins, hormone-like molecules that are critical for implantation of an early embryo in the uterus, the study team writes in the American Journal of Obstetrics & Gynecology.

“The category of NSAID medications was invented to relieve pain and reduce inflammation. The way this category of medications accomplishes these pharmacologic effects is by inhibiting the production of prostaglandin,” said lead study author Dr. De-Kun Li, a researcher with Kaiser Permanente Northern California in Oakland.

“It turns out that a sufficient amount of prostaglandin needs to be present for successful embryonic implantation. Thus, a reduced amount of prostaglandin due to NSAID use around the time of conception could lead to difficulties of implantation of the embryo, and miscarriage,” Li said in an email.

The connection between NSAIDs’ pharmacologic effect of inhibiting prostaglandin production to increased risk of miscarriage is not well known yet, Li noted.

NSAIDs such as ibuprofen, naproxen, diclofenac and celecoxib are available by prescription and over the counter and are commonly used to relieve fever and pain. They are also among the most commonly used drugs by pregnant women, the study team notes.

To assess the effects of NSAID use early in pregnancy, Li and colleagues recruited 241 women who took only NSAIDs around the time of conception and during the first 20 weeks of pregnancy, 391 who took only acetaminophen during this period and 465 women who took neither type of medication. The women were, on average, 39 days pregnant.

About 24 percent of the women who took NSAIDs had miscarriages within the first 20 weeks of pregnancy, compared with 16 percent of women who took acetaminophen and 17 percent of women who took neither medication.

After accounting for other factors that can influence miscarriage risk, including age, caffeine intake, smoking during pregnancy, multivitamin use, fevers and other health issues, the researchers found that overall, women who took NSAIDS had a 59 percent higher risk of miscarriage than women who took no painkillers.

NSAID users also had a 45 percent higher miscarriage risk than acetaminophen users.

When researchers looked at timing, the added risk was almost entirely among women who used NSAIDs around the time of conception, and these miscarriages were most likely to be within the first eight weeks of pregnancy.

The degree of risk also increased for women who used NSAIDs for two weeks or more compared with those who took them for less time.

“If pregnant women are concerned about NSAID use around conception, they should talk with their clinicians about their concern,” said Dr. Tracy Flanagan, director of Women’s Health at Kaiser Permanente Northern California in Richmond, who wasn’t involved in the study.

She pointed out that although there is a plausible mechanism for how NSAID use would lead to a higher risk of miscarriage, a study like this can only show an association, it doesn’t prove causation.

“Overall, this study is a step forward for this research area, but a systematic review of this and the previous studies that have been done on this topic might help to clarify the role of painkillers on miscarriage,” said Anne Marie Jukic, a researcher at the School of Public Health at Yale Universtiy in New Haven, Connecticut, who wasn’t involved in the study.

The FDA recommends that women consult with their healthcare providers before taking pain medicines during pregnancy, whether over-the-counter or prescription, Jukic said in an email.

SOURCE: bit.ly/2JY1M3W American Journal of Obstetrics & Gynecology, online June 8, 2018.