title: Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study.
abstract: OBJECTIVE
  To determine whether use of antiepileptic drugs during pregnancy may increase the risk of spontaneous abortion or stillbirth.
  
  
  METHODS
  Population based cohort study.
  
  
  METHODS
  Register based study in Denmark, 1997-2008.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, DK 8000 Aarhus C, Denmark bhb@ph.au.dk.
authors.forename: Bodil Hammer
authors.initials: BH
authors.lastname: Bech
authors.affiliation: Section for Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: Maiken Ina Siegismund
authors.initials: MI
authors.lastname: Kjaersgaard
authors.affiliation: Research Unit for General Practice and Section for General Medical Practice, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: Henrik Søndergaard
authors.initials: HS
authors.lastname: Pedersen
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA.
authors.forename: Penelope P
authors.initials: PP
authors.lastname: Howards
authors.affiliation: Regional Center of Child and Adolescent Psychiatry, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Merete Juul
authors.initials: MJ
authors.lastname: Sørensen
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, DK 8000 Aarhus C, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Olsen
authors.affiliation: Section for Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: Erik Thorlund
authors.initials: ET
authors.lastname: Parner
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, DK 8000 Aarhus C, Denmark Department of Clinical Medicine-Obstetrics and Gynaecology, Aarhus University, Aarhus, Denmark.
authors.forename: Lars Henning
authors.initials: LH
authors.lastname: Pedersen
authors.affiliation: Research Unit for General Practice and Section for General Medical Practice, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: Mogens
authors.initials: M
authors.lastname: Vestergaard
authors.affiliation: Department of Neurology, Aarhus University Hospital, Aarhus, Denmark Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Christensen
mesh_terms: D000022:Abortion, Spontaneous / Q000139:chemically induced / Q000453:epidemiology*; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D004827:Epilepsy / Q000188:drug therapy / Q000453:epidemiology; D005260:Female; D006801:Humans; D016017:Odds Ratio; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000453:epidemiology; D012042:Registries; D012044:Regression Analysis; D050497:Stillbirth / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants