BMJ  2003;327:368 (16 August), doi:10.1136/bmj.327.7411.368

Paper

Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study

De-Kun Li, epidemiologist1, Liyan Liu, programmer analyst1, Roxana Odouli, research associate1

1 Division of Research, Kaiser Foundation Research Institute, Kaiser Permanente, 2000 Broadway, Oakland, California 94612, USA

Correspondence to: D-K Li dkl{at}dor.kaiser.org

Objective To evaluate whether prenatal use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of miscarriage.

Design Population based cohort study. Prenatal use of NSAIDs, aspirin, and paracetamol (acetaminophen) ascertained by in-person interview.

Setting Kaiser Permanente Medical Care Program, a healthcare delivery system, in the San Francisco area of the United States.

Participants 1055 pregnant women recruited and interviewed immediately after their positive pregnancy test. Median gestational age at entry to the study was 40 days.

Main outcome measures Pregnancy outcomes up to 20 weeks of gestation.

Results 53 women (5%) reported prenatal NSAID use around conception or during pregnancy. After adjustment for potential confounders, prenatal NSAID use was associated with an 80% increased risk of miscarriage (adjusted hazard ratio 1.8 (95% confidence interval 1.0 to 3.2)). The association was stronger if the initial NSAID use was around the time of conception or if NSAID use lasted more than a week. Prenatal aspirin use was similarly associated with an increased risk of miscarriage. However, prenatal use of paracetamol, pharmacologically different from NSAIDs and aspirin, was not associated with increased risk of miscarriage regardless of timing and duration of use.

Conclusion Prenatal use of NSAIDs and aspirin increased the risk of miscarriage. These findings need confirmation in studies designed specifically to examine the apparent association.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to StumbleUpon StumbleUpon   Add to Technorati Technorati    What's this?

Relevant Articles

NSAIDs during pregnancy and risk of miscarriage: True risks or only suspicions?
Benedetta Schiavetti, Antonio Clavenna, Rita Campi, and Maurizio Bonati
BMJ 2004 328: 108. [Extract] [Full Text]

Danish group reanalyses miscarriage in NSAID users
Gunnar Lauge Nielsen, Mette Vinther Skriver, Lars Pedersen, and Henrik Toft Sørensen
BMJ 2004 328: 109. [Extract] [Full Text]

Use of NSAIDs in pregnancy increases risk of miscarriage
BMJ 2003 327: 0. [Full Text] [PDF]

This article has been cited by other articles:

  • Mikkelsen, E. M, Hatch, E. E, Wise, L. A, Rothman, K. J, Riis, A., Sorensen, H. T. (2009). Cohort Profile: The Danish Web-based Pregnancy Planning Study--'Snart-Gravid'. Int J Epidemiol 38: 938-943 [Full text]  
  • Rebordosa, C., Kogevinas, M., Bech, B. H, Sorensen, H. T, Olsen, J. (2009). Use of acetaminophen during pregnancy and risk of adverse pregnancy outcomes. Int J Epidemiol 38: 706-714 [Abstract] [Full text]  
  • Dirckx, K., Cabri, P., Merien, A., Galajdova, L., Gerris, J., Dhont, M., De Sutter, P. (2009). Does low-dose aspirin improve pregnancy rate in IVF/ICSI? A randomized double-blind placebo controlled trial. Hum Reprod 24: 856-860 [Abstract] [Full text]  
  • Li, D., Liu, L., Odouli, R. (2009). Presence of depressive symptoms during early pregnancy and the risk of preterm delivery: a prospective cohort study. Hum Reprod 24: 146-153 [Abstract] [Full text]  
  • Gelbaya, T.A., Kyrgiou, M., Li, T.C., Stern, C., Nardo, L.G. (2007). Low-dose aspirin for in vitro fertilization: a systematic review and meta-analysis. Hum Reprod Update 13: 357-364 [Abstract] [Full text]  
  • Jauniaux, E., Farquharson, R. G., Christiansen, O. B., Exalto, N., On behalf of ESHRE Special Interest Group for Earl, (2006). Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod 21: 2216-2222 [Abstract] [Full text]  
  • Wang, H., Dey, S. K., Maccarrone, M. (2006). Jekyll and Hyde: Two Faces of Cannabinoid Signaling in Male and Female Fertility. Endocr. Rev. 27: 427-448 [Abstract] [Full text]  
  • Khairy, P., Ouyang, D. W., Fernandes, S. M., Lee-Parritz, A., Economy, K. E., Landzberg, M. J. (2006). Pregnancy Outcomes in Women With Congenital Heart Disease. Circulation 113: 517-524 [Abstract] [Full text]  
  • Gris, J.-C., Mercier, E., Quere, I., Lavigne-Lissalde, G., Cochery-Nouvellon, E., Hoffet, M., Ripart-Neveu, S., Tailland, M.-L., Dauzat, M., Mares, P. (2004). Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood 103: 3695-3699 [Abstract] [Full text]  
  • Burdan, F (2004). Developmental effects of propyphenazone in analgesic and antipyretic combination with caffeine or paracetamol. Hum Exp Toxicol 23: 235-244 [Abstract]  
  • Sacks, G.P., Seyani, L., Lavery, S., Trew, G. (2004). Maternal C-reactive protein levels are raised at 4 weeks gestation. Hum Reprod 19: 1025-1030 [Abstract] [Full text]  
  • Wang, H., Ma, W.-g., Tejada, L., Zhang, H., Morrow, J. D., Das, S. K., Dey, S. K. (2004). Rescue of Female Infertility from the Loss of Cyclooxygenase-2 by Compensatory Up-regulation of Cyclooxygenase-1 Is a Function of Genetic Makeup. J. Biol. Chem. 279: 10649-10658 [Abstract] [Full text]  
  • Nielsen, G. L., Skriver, M. V., Pedersen, L., Sorensen, H. T. (2004). Danish group reanalyses miscarriage in NSAID users. BMJ 328: 109-109 [Full text]  
  • Schiavetti, B., Clavenna, A., Campi, R., Bonati, M. (2004). NSAIDs during pregnancy and risk of miscarriage: True risks or only suspicions?. BMJ 328: 108-108 [Full text]  
  • (2004). Other articles noted: 25 Jul 03 to 7 Nov 03. Evid. Based Nurs. 7: e1-1 [Full text]  
  • Li, D.-K., Janevic, T., Odouli, R., Liu, L. (2003). Li et al. Respond to "No Link between Hot Tubs and Miscarriage". Am J Epidemiol 158: 941-941 [Full text]  
  • (2003). Does NSAID Use Increase Risk for Miscarriage?. JWatch General 2003: 5-5 [Full text]  

Rapid Responses:

Read all Rapid Responses

Aspirin and miscarriage
Marjory A MacLean
bmj.com, 15 Aug 2003 [Full text]
Recurrent miscarriage
Danny Tucker
bmj.com, 17 Aug 2003 [Full text]
Job vacancy :To oversee media interpretation of research evidence for the international community!
Sachin Maiti
bmj.com, 18 Aug 2003 [Full text]
Asprin use to prevent miscarriage
David J. D'Souza
bmj.com, 18 Aug 2003 [Full text]
Authors' reply: Aspirin and miscarriage
De-Kun Li, et al.
bmj.com, 19 Aug 2003 [Full text]
Low-Dose Aspirin and Miscarriage
Andrea L. D. Webster
bmj.com, 19 Aug 2003 [Full text]
anti-inflammatory drugs and pregnancy
Monika Malhotra, et al.
bmj.com, 20 Aug 2003 [Full text]
Questions regarding methodologic details
Mark A. Klebanoff, et al.
bmj.com, 20 Aug 2003 [Full text]
Authors' replay: Questions regarding methodological details
De-Kun Li, et al.
bmj.com, 29 Aug 2003 [Full text]
Do non-steroidal anti-inflammatory drugs increase the risk of miscarriage?
Hasan I. Atrah
bmj.com, 5 Sep 2003 [Full text]
Use of non-steroidal anti-inflammatory drugs before and during pregnancy
Heather C. Nix
bmj.com, 10 Sep 2003 [Full text]
Re-analysis of risk of miscarriage in users of NSAIDs; a register based case-control study
Gunnar Lauge Nielsen, et al.
bmj.com, 1 Dec 2003 [Full text]
True risks or only suspicions?
Benedetta F Schiavetti, et al.
bmj.com, 19 Nov 2003 [Full text]
Authors’ reply: True risks or only suspicions
De-Kun Li, et al.
bmj.com, 16 Dec 2003 [Full text]
One burning question
Jennifer Kuzma
bmj.com, 11 Jan 2004 [Full text]



Access jobs at BMJ Careers
Whats new online at Student 

BMJ