Rationale and Comments

The risks to an unborn child from valproate are significant enough to warrant avoiding this medication if at all possible. If valproate is deemed necessary, aim for lowest effective dose. Females on valproate should receive risk counseling prior to conception including possibility of major malformations from first trimester exposure, and long-term cognitive and behavioral effects (lower IQ and increased risk of autism spectrum disorder and attention-deficit/hyperactivity disorder) throughout pregnancy.

Sponsoring Organizations

• American Epilepsy Society

Sources

• Expert consensus

Disciplines

• Neurologic

References

• Campbell E1, Kennedy F2, Russell A3, Smithson WH4, Parsons L5, Morrison PJ6, Liggan B7, Irwin B1, Delanty N8, Hunt SJ1, Craig J1, Morrow J1. Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers. J Neurol Neurosurg Psychiatry. 2014;85(9):1029-34. Epub 2014 Jan 20.
  
• Hernández-Díaz S1, Smith CR, Shen A, Mittendorf R, Hauser WA, Yerby M, Holmes LB; North American AED Pregnancy Registry; North American AED Pregnancy Registry.
  
• Comparative safety of antiepileptic drugs during pregnancy. Neurology. 2012;78(21):1692-9. Epub 2012 May 2.
  
• Tomson T1, Battino D, Bonizzoni E, Craig J, Lindhout D, Sabers A, Perucca E, Vajda F; EURAP study group. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol. 2011;10(7):609-17. Epub 2011 Jun 5.
  
• Tomson T1, Marson A2,3, Boon P4, Canevini MP5, Covanis A6, Gaily E7, Kälviäinen R8,9, Trinka E10,11,12. Valproate in the treatment of epilepsy in girls and women of childbearing potential. Epilepsia. 2015;56(7):1006-19. Epub 2015 May 16.