Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort studyBMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g5159 (Published 22 August 2014) Cite this as: BMJ 2014;349:g5159
- Bodil Hammer Bech, associate professor1,
- Maiken Ina Siegismund Kjaersgaard, PhD student2,
- Henrik Søndergaard Pedersen, statistician3,
- Penelope P Howards, assistant professor4,
- Merete Juul Sørensen, consultant5,
- Jørn Olsen, professor1,
- Erik Thorlund Parner, professor2,
- Lars Henning Pedersen, adjunct associate professor16,
- Mogens Vestergaard, professor3,
- Jakob Christensen, senior registrar78
- 1Section for Epidemiology, Department of Public Health, Aarhus University, DK 8000 Aarhus C, Denmark
- 2Section for Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark
- 3Research Unit for General Practice and Section for General Medical Practice, Department of Public Health, Aarhus University, Aarhus, Denmark
- 4Department of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA
- 5Regional Center of Child and Adolescent Psychiatry, Aarhus University Hospital, Risskov, Denmark
- 6Department of Clinical Medicine–Obstetrics and Gynaecology, Aarhus University, Aarhus, Denmark
- 7Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
- 8Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark
- Correspondence to: B H Bech
- Accepted 3 August 2014
Objective To determine whether use of antiepileptic drugs during pregnancy may increase the risk of spontaneous abortion or stillbirth.
Design Population based cohort study.
Setting Register based study in Denmark, 1997-2008.
Participants 983 305 pregnancies identified in the Danish medical birth register and the Danish national hospital discharge register from 1 February 1997 to 31 December 2008 were linked to the Danish Register of Medicinal Product Statistics to obtain information on use of antiepileptic drugs.
Main outcome measures Risk ratio of spontaneous abortion and stillbirth after use of antiepileptic drugs during pregnancy, estimated by using binomial regression adjusting for potential confounders of maternal age, cohabitation, income, education, history of severe mental disorder, and history of drug misuse.
Results Antiepileptic drugs were used in a total of 4700 (0.5%) pregnancies. 16 out of 100 pregnant women using antiepileptics and 13 out of 100 pregnant women not using antiepileptics experienced a spontaneous abortion. After adjusting for potential confounders pregnant women using antiepileptics had a 13% higher risk of spontaneous abortions than pregnant women not using antiepileptics (adjusted risk ratio 1.13, 95% confidence interval 1.04 to 1.24). However, the risk of spontaneous abortion was not increased in women with an epilepsy diagnosis (0.98, 0.87 to 1.09), only in women without a diagnosis of epilepsy (1.30, 1.14 to 1.49). In an analysis including women with at least two pregnancies with discordant antiepileptic drug use (for example, use in the first pregnancy but not in the second), the adjusted hazard ratio for spontaneous abortion was 0.83 (0.69 to 1.00) for exposed pregnancies compared with unexposed pregnancies. Stillbirth was identified in 18 women who used antiepileptic drugs (unadjusted risk ratio 1.29, 0.80 to 2.10).
Conclusion Among women with epilepsy and when analysing the risk in antiepileptic drug discordant pregnancies in the same woman, we found no overall association between the use of antiepileptic drugs during pregnancy and spontaneous abortions. Therefore unmeasured confounding may explain the slight increased risk for spontaneous abortion with any antiepileptic drug use (among women both with and without epilepsy). We found no association between antiepileptic drug use during pregnancy and stillbirth, but the statistical precision was low.
Contributors: BHB, MISK, MJS, JO, ETP, LHP, MV, and JC conceived and designed the study. LHP and JC acquired the data. All authors contributed to the analyses and interpretation of data and drafting the manuscript. BHB is guarantor.
Funding: JC receives research support from the Danish Epilepsy Association. LHP is supported by a Sapere Aude–Postdoc grant from the Danish Council for Independent Research. The funding sources had no role in the design and conduct of the study; the collection, analysis and interpretation of data; or the preparation, review, or approval of the manuscript.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; JC received honorariums for giving lectures and serving on the scientific advisory board of UCB Nordic and Eisai, and received funding for a trip from UCB Nordic; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: This study was approved by the Danish Data Protection Agency. Ethical approval was not required as this was a registry study.
Data sharing: No additional data available.
Transparency: The lead author (BHB) affirms that this manuscript is an honest, accurate and transparent account of the study being reported and that no aspects have been omitted.
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