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Case control study
Use of non-aspirin NSAIDs during pregnancy may increase the risk of spontaneous abortion
  1. Pamela Verma1,
  2. Christine A Clark2,
  3. Karen A Spitzer2,
  4. Carl A Laskin2,
  5. Joel Ray1,
  6. Gideon Koren3
  1. 1Department of Medicine St. Michael's Hospital, Ontario, Canada
  2. 2Mount Sinai Hospital and LifeQuest Centre for Reproductive Medicine, Ontario, Canada
  3. 3Division of Clinical Pharmacology/Toxicology, Hospital for Sick Children, Toronto, Canada
  1. Correspondence to Gideon Koren
    The Motherisk Program, Division of Clinical Pharmacology/Toxicology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; gideon.koren{at}

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Implications for practice and research

  • Data from this study support the assertion that the use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy is associated with increased risk of spontaneous abortion and should, therefore, be used with caution.

  • However, other factors such as socio-economic status and co-existing illnesses may have biased these results.

  • Further research is needed to explore the effect of taking NSAIDs during pregnancy and the other factors identified.

  • Future research should include data relating to the use of both prescription and over-the-counter NSAIDs.


NSAIDs are one of the commonest classes of drugs taken by pregnant women. Data about the risks associated with this remains equivocal. The study by Nakhai-Pour et al explored whether the use of NSAIDs during pregnancy is associated with increased risk of spontaneous abortion.


This study examined data from one Province in Canada extracted from a provincial database. Women who had had a spontaneous abortion (n=4705) were matched with 47 050 controls. The use of NSAIDs was measured by whether or not the women filled a prescription for them during their pregnancy. Statistical analysis was carried out to explore whether there was any association between the use of non-aspirin NSAIDs and the risk of spontaneous abortion.


The use of NSAIDs during pregnancy appeared to be associated with increased risk of spontaneous abortion among the women included in the study. Other findings indicated that spontaneous abortions were more common among (slightly) older women living in an urban received social assistance who had other co-existing healthcare conditions. Women who had a spontaneous abortion had had fewer prenatal visits and were taking more prescription medications than women who did not.


This study has several limitations. First, the participants were more economically disadvantaged, had more medical problems and more likely to smoke compared with other Canadian women.1 The authors state that these women account for 43% of the overall population, and 36% of pregnant women in the province. These numbers greatly contradict similar figures from a recent study by the same group.1 Moreover, Nakhai-Pour and colleagues' initial paper concluded that the ‘substantial differences between pregnant women insured by the RAMQ-Rx and those insured by private drug insurance plans’ would ‘most likely limit generalisability’ of studies using the RAMQ database.1

Second, the frequently used term ‘index date’ is difficult to interpret; is it the point at which the patient began spotting (or cramping) or when she had passed the aborted tissue? Clearly, this definition is critical, as NSAIDs may be prescribed for pain after the start of the spontaneous abortion − mitigating the claim that NSAID is the cause. Third, filling a prescription does not adequately represent actual use of the drug. The authors were unable to assess over-the-counter (OTC) NSAID usage. OTC medication use is extremely common during pregnancy (eg, ibuprofen). Until a study includes both OTC and prescription NSAID use it will not be possible to get a clear picture of potential harm.

Fourth, the authors stated that ‘to their knowledge’, neither smoking nor body mass index (BMI) are risk factors for spontaneous abortion, and therefore, were not adjusted for. However, maternal, paternal and environmental exposure to smoking are all associated with increased incidence of spontaneous abortion.2 Moreover, patients with a BMI>25 kg/m2 have significantly higher odds of spontaneous abortion.3 4 The lack of consideration of these covariates makes the findings less credible.

In summary, the poor quality of this study forestalls its use for counselling women who are planning to get pregnant or who have conceived while on NSAIDs. The study is not representative of Canadian women. With few other analgesic options, the message conveyed may prevent many women from using NSAIDs when needed and introduces the potential for guilt in the event of a spontaneous pregnancy loss.


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  • Competing interests None.

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