Valproate-associated foetal malformations-Rates of occurrence, risks in attempted avoidance.

Abstract:

OBJECTIVES:To gain insight into the main advantages and disadvantages that might result from valproate being unavailable for women who intend to become pregnant. MATERIALS AND METHODS:Analysis of data from the Australian Pregnancy Register concerning pregnancies exposed to valproate (N = 501) and pregnancies where previous valproate intake had been ceased before pregnancy (N = 101). RESULTS:The risk of foetal malformation associated with valproate exposure during pregnancy was dose-related, and there was a tendency for the more major malformations, including those often managed by therapeutic abortion, for example spina bifida, to occur at higher valproate doses. Had there been no exposure to valproate during pregnancy, some 80% of the foetal malformations that occurred might have been avoided. Cessation of previous valproate therapy before pregnancy was associated with an increased hazard of seizure-affected pregnancy. This was particularly the case for women with generalized epilepsies, in whom the incidence of seizure-affected pregnancy was increased by 50% to nearly 100%. CONCLUSIONS:Avoiding valproate intake during pregnancy is likely to reduce the incidence of foetal malformation, but at a cost of worsened maternal epilepsy control. Individualization of treatment is particularly important in considering withdrawal of valproate in the light of the fact that it is much more widely used in generalized epilepsy, there being fewer alternative drugs than for focal epilepsy and withdrawal is not without risk for both mother and baby. This study may provide a quantitative basis for assessing the balance between benefit and disadvantage for individual women with valproate-treated epilepsy who are considering pregnancy.

journal_name

Acta Neurol Scand

authors

Vajda FJE,O'Brien TJ,Graham JE,Hitchcock AA,Lander CM,Eadie MJ

doi

10.1111/ane.13005

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

42-48

issue

1

eissn

0001-6314

issn

1600-0404

journal_volume

139

pub_type

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