Editor—Li et al reported that use of non-steroidal anti-inflammatory drugs (NSAIDs) in the first half of pregnancy is associated with an 80% increased risk of miscarriage, which is in accordance with our previous results.1,2
We have since accessed a recent update of our dataset covering 1998-2002, including gestational age, which was not originally accessible.
We obtained data on miscarriage, and birth and drug exposure were obtained from a hospital discharge registry and a prescription database).2 We identified 1599 women with first recorded miscarriage, of whom 45 had filled prescriptions for NSAIDs in the last 12 weeks before the miscarriage. As controls we used 10 primigravidas delivering after the 28th gestational week in the corresponding gestational period (n = 15 990).
Cases and controls were classified as drug exposed if they had redeemed NSAID prescriptions at appropriate gestational periods. We assessed the association between miscarriage and NSAID use in five periods before miscarriage and found a consistently positive association between miscarriage and exposure to NSAIDs in the weeks before miscarriage, with odds ratios from 3.35 to 0.58 (table).
Table 1.
Association between miscarriage and NSAID use as assessed in five periods before miscarriage
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Without gestational age2
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Including gestational age (new analysis)
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|---|---|---|---|---|---|---|
| Week before miscarriage | Odds ratio | 95% CI | Cases exposed to NSAIDs (n=1554) | Controls exposed to NSAIDs (n=15 677) | Odds ratio | 95% CI |
| 1 | 6.99 | 2.75-17.74 | 3 | 8 | 3.35 | 0.88 to 12.79 |
| 2-3 | 3.00 | 1.21-7.44 | 5 | 33 | 1.50 | 0.58 to 3.86 |
| 4-6 | 4.38 | 2.66-7.20 | 18 | 122 | 1.50 | 0.91 to 2.47 |
| 7-9 | 2.69 | 1.81-4.00 | 16 | 100 | 1.59 | 0.93 to 2.70 |
| 10-12 | 1.26 | 0.85-1.87 | 3 | 50 | 0.58 | 0.18 to 1.85 |
NSAIDs=non-steroidal anti-inflammatory drugs.
Sampling on the specific gestational age substantially reduced the strength of our previously reported association between use of NSAIDs and risk of miscarriage. However, the association remains consistently positive in all analysed time periods, with a trend towards a stronger association when looking at the periods closer to the miscarriage. Whether this association is caused directly by NSAIDs or by the indication for prescribing the drug is still not solved.
Competing interests: None declared.
References
- 1.Li DK, Liu L, Odouli R. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study. BMJ 2003;327: 368-72. (16 August.) [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Nielsen GL, Sørensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs. a population based observational study and case-control study. BMJ 2001;322: 266-70. [DOI] [PMC free article] [PubMed] [Google Scholar]