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Non-aspirin pain relievers linked to risk of pregnancy loss

Researchers say medications such as ibuprofen and naproxen might be linked to pregnancy loss during the first 20 weeks.

Researchers studying a large population of women in Quebec have reported identifying a link between medications such as ibuprofen and naproxen and pregnancy loss during the first 20 weeks.

The research, published September 6, 2011, in the Canadian Medical Association Journal, found that women who filled prescriptions for the so-called non-steroidal anti-inflammatory drugs (NSAIDs) had a risk of spontaneous abortion (the medical term for pregnancy loss before a certain period) that was almost 2.5 times greater than women who did not.

Investigators Hamid Reza Nakhai-Pour, Perrine Broy, Odile Sheehy, and Anick Bérard examined the medical records of 4,705 women who had experienced a spontaneous abortion, each of them compared against records of 10 matched women who had not experienced a fetal loss. In the group of women who had lost a pregnancy, 352 had filled prescriptions for NSAIDs such as naproxen, ibuprofen, rofecoxib, diclofenac, celocoxib, or “other.” In Quebec, where the records were obtained from the Quebec Pregnancy Registry, the only one of the NSAIDs that is available over the counter is ibuprofen. Among the 47,050 women who had not experienced a fetal loss, there were 1,213 who had filled such a prescription.

The researchers then adjusted their analyses for other factors that might affect spontaneous abortion, such as diabetes or high blood pressure. After this adjustment left only the NSAID prescriptions as a factor, they still found higher risk of fetal loss among the women who had filled such a prescription. The medical records provided no information about whether or not the women actually took the prescribed medication or how much they may have taken, and there also was no information about whether women in either group acquired ibuprofen or aspirin over the counter.

Among the NSAIDs assessed, diclofenac had the strongest mathematical association with spontaneous abortion, showing a threefold increase in risk. Ibuprofen was associated with a twofold increase in risk.

A link between NSAID use and pregnancy loss is not a new finding, as previous work has suggested increased risk with the use of NSAIDs around the time of conception. What that previous study and the current work do not establish is whether or not NSAIDs cause the loss or if some other process already threatening the pregnancy leads women to seek pain relief. It’s always important to remember that studies like these show only a mathematical association and do not directly show cause and effect. The authors of the current study suggest that NSAIDs may trigger pregnancy loss by altering levels of certain chemicals called prostaglandins that are usually suppressed during most of pregnancy, but that idea remains purely speculation at this point.

The authors discuss some limitations of their study, which included the lack of any information about what the women in either group actually took, either via the prescriptions recorded in their medical information or over the counter. They also had no information on specifics such as each woman’s body mass index or smoking habits or whether they took aspirin. The authors state that to their knowledge, there is no association between BMI or smoking and spontaneous abortion. Yet results from other studies have in fact identified a statistical link between smoking and pregnancy loss and a possible link between obesity and miscarriage. Not having that information certainly constitutes a study limitation, as either factor could be related to seeking pain relief. Muddying up the findings even more is the fact that the authors found no link between dose (presumably based on prescription data) and rate of pregnancy loss.

Bottom line: Hamid Reza Nakhai-Pour and colleagues examined the medical records of women who had experienced spontaneous abortion (loss in the first 20 weeks of pregnancy) and compared their NSAID prescription history to that of ten times as many women who had not experienced a pregnancy loss. The authors did not have access to specific information about how much of any NSAID women had taken or whether women had used over-the-counter ibuprofen or aspirin. What Nakhai-Pour and colleagues identified was a mathematical association between having filled NSAID prescriptions and the risk of spontaneous abortion. The study did not address cause and effect and did not assess whether some other factor – including those that might lead women to seek pain relief – might be the causative influence in the fetal losses. The take-home message is the same as it has always been for NSAIDs and pregnancy: Discuss your needs and the potential cost-benefits with your healthcare provider.

Emily Willingham