Valproate and the risk for congenital malformations: Is formulation and dosage regime important

Seizure - European Journal of Epilepsy, 03/01/2012

Prescribing controlled release valproate or multiple daily administrations in pregnancy did not reduce the risk for malformations. Higher malformation rates observed with in utero exposure to valproate are more likely related to total daily dose, rather than peak serum levels.


  • The UK Epilepsy and Pregnancy Register is a prospective, observational and follow up study set up to determine the risks of major congenital malformations for infants exposed to antiepileptic drugs in utero.
  • In this study the authors have extracted data for those pregnancies exposed to valproate in monotherapy.
  • They have calculated malformation rates and relative risks as a function of valproate exposure.


  • Outcome data were available for 1109 pregnancies exposed to valproate in monotherapy.
  • Exposure to 1000mg a day or more of valproate was associated with almost double the risk of major congenital malformation compared with daily valproate doses below 1000mg daily (8.86% vs 4.88%, RR: 1.7; 95% CI: 1.1-2.9).
  • There were no differences in the risks for malformations between standard release valproate and controlled release valproate preparations (RR: 1.11; 95% CI: 0.67-1.83) or for those exposed to single or multiple daily administrations (RR: 0.99, 95% CI: 0.58-1.7

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