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 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 the Kaiser Foundation Research Institute of 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.
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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: https://bit.ly/2JY1M3W American Journal of Obstetrics &
Gynecology, online June 8, 2018.
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