title: The teratogenicity of the newer antiepileptic drugs - an update.
abstract: OBJECTIVE
  To assess the risk of teratogenicity from maternal intake of the more widely used newer antiepileptic drugs, especially lamotrigine, levetiracetam and topiramate.
  
  
  METHODS
  Use of confidence interval and regression methods to compare risks of foetal malformation in pregnancies in women exposed (n = 1572) and in women with epilepsy not exposed (n = 153) to antiepileptic drugs in the first trimester.
  
  
  RESULTS
  Compared with the foetal malformation rate in women with epilepsy who were untreated in the first trimester (3.3%), the malformation rates for lamotrigine (4.6%), levetiracetam (2.4%) and topiramate (2.4%), all in monotherapy, were not statistically significantly different. However, the malformation rates for topiramate as part of polytherapy (14.1%) and for valproate in both monotherapy (13.8%) and polytherapy (10.2%) were statistically significantly higher. Regression analysis of combined monotherapy and polytherapy data showed no statistically significant increased risk of teratogenesis associated with lamotrigine or levetiracetam, but a statistically significant and dose-related risk for first trimester topiramate (P = 0.01) and valproate (P < 0.0001) exposure.
  
  
  CONCLUSIONS
  Evidence from this and other studies suggests that lamotrigine and levetiracetam have low risk for teratogenesis, but that topiramate exposure early in pregnancy may be associated with dose-related anatomical teratogenesis, as valproate is already known to be.
authors.affiliation: Departments of Medicine and Neurology, Royal Melbourne Hospital, University of Melbourne, Parkville, Vic., Australia.
authors.forename: F J E
authors.initials: FJ
authors.lastname: Vajda
authors.forename: T J
authors.initials: TJ
authors.lastname: O'Brien
authors.forename: C M
authors.initials: CM
authors.lastname: Lander
authors.forename: J
authors.initials: J
authors.lastname: Graham
authors.forename: M J
authors.initials: MJ
authors.lastname: Eadie
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology* / Q000209:etiology; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D000077213:Lamotrigine; D000077287:Levetiracetam; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives; D011247:Pregnancy; D012042:Registries; D012306:Risk; D000077236:Topiramate; D014227:Triazines / Q000009:adverse effects; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D000077287:Levetiracetam; D014635:Valproic Acid; D000077213:Lamotrigine; D010889:Piracetam
keywords: lamotrigine; levetiracetam; malformation; pregnancy; teratogenesis; topiramate