Dose-dependent teratogenicity of valproate in mono-and polytherapy

Torbjörn Tomson, Dina Battino, Erminio Bonizzoni, John Craig, Dick Lindhout, Emilio Perucca, Anne Sabers, Sanjeev V. Thomas, Frank Vajda

Research output: Contribution to journalArticlepeer-review


Objective: To assess the risk of major congenital malformations (MCMs) in association with maternal use of valproic acid (VPA) in monotherapy or adjunctive therapy, and its relationship with dose. Methods: The analysis was based on prospectively acquired data from EURAP, a registry enrolling women treated with antiepileptic drugs (AEDs) in early pregnancy, in which the primary outcome is presence of MCMs at 1 year after birth. Exposure was defined as type and dose of AEDs at time of conception. A comparison was made among 3 exposure types: (1) VPA monotherapy (n 1,224); (2) VPA combined with lamotrigine (LTG) (n 159); and (3) VPA combined with another AED but not LTG (n 205). Results: The frequency of MCMs at 1 year after birth was 10.0% for VPA monotherapy, 11.3% for exposures to VPA and LTG, and 11.7% for exposures to VPA + another (non-LTG) AED. Regardless of exposure group, the frequency of MCMs increased with dose of VPA, being highest at doses ≥1,500 mg/d (24.0% for monotherapy, 31.0% for VPA + LTG, and 19.2% for VPA + other AEDs), and was similar across treatment groups at the lowest VPA dose level of

Original languageEnglish
Pages (from-to)866-872
Number of pages7
Issue number10
Publication statusPublished - Sep 8 2015

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)


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