Women who take nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy are not at increased risk of miscarriages, according to a new Israeli study published in CMAJ (Canadian Medical Association Journal).
The Ben-Gurion University of the Negev researchers noted that the use of NSAIDs, both prescription and over-the-counter, is increasing among pregnant women. Yet, it has been unclear whether the medicines — which include ibuprofen, naproxen, diclofenac and others — increase the risk of pregnancy loss because previous studies have shown inconsistent results.
To determine whether there is an association between the use of NSAIDs in pregnancy and miscarriage (spontaneous abortion), the BGU researchers looked at data on 65,457 women aged 15 to 45 years who were admitted to Soroka University Medical Center in Beersheva between January 2003 and December 2009 to give birth (90 percent of women) or for a miscarriage (10%).

Of the total group, 4,495 (6.9%) of women took NSAIDs during the first trimester of pregnancy. The study showed that women who took NSAIDs were older, were more likely to smoke and had more inflammatory diseases. In addition, more pregnant women in the exposed group had undergone in-vitro fertilization (IVF) than in those who did not take NSAIDs.
“We found no important associations between exposure to NSAIDs, either by group or for most specific NSAID drugs, and risk of spontaneous abortion,” write Dr. Sharon Daniel and Prof. Amalia Levy, Department of Public Health, Ben-Gurion University of the Negev and Soroka University Medical Center, with coauthors.
The results showed that about 8.2% of women in the group exposed to general anti-inflammatories had miscarriages compared with 10% of women in the group that did not take NSAIDs.
The authors cited two other studies that reported an increased risk of spontaneous abortion following exposure to NSAIDs and highlighted the fact that they “did not adjust for important known risk factors for spontaneous abortion, including hypercoagulable state, uterine disorders, the presence on an intrauterine device and IVF, which have been found to be associated with spontaneous abortions.”
The new study took these factors into consideration.

“The fact that the study was based on a large proportion of the district population, was adjusted to nearly all known risk factors for miscarriages (tobacco use, obesity, IVF, uterine malformations, hypercoagulable conditions, intrauterine contraceptive device etc.) and used advanced statistical methods strengthens the validity of the results,” says the principal investigator, epidemiologist Prof. Levy.
The researchers did raise a new question about indomethacin, specifically.
The study showed that in the group of women who took COX-2 selective inhibitors, which target specific inflammation, 17% had a miscarriage. The scientists said that although this group was small, the question needs further research.”We found an increased risk of spontaneous abortion following exposure to indomethacin,” they wrote.
The authors believe that this may be due to “reverse causation bias” because indomethacin was dispensed at the end of pregnancy, likely to treat preterm labor, an indication different than that for other NSAIDS.

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