Valproic acid in epilepsy : Pregnancy-related issues

• Published in: Drug safety 2006, Vol.29 (1), p.1-21
• Main Authors: GENTON, Pierre, SEMAH, Franck, TRINKA, Eugen
• Format: Article
• Language: English
• Subjects: Abnormalities, Drug-Induced - etiology; Anticonvulsants - adverse effects; Anticonvulsants - blood; Anticonvulsants - therapeutic use; Autistic Disorder - chemically induced; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Epilepsy - drug therapy; Female; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Infant, Newborn; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Nervous system (semeiology, syndromes); Neurology; Pharmacology. Drug treatments; Pregnancy; Pregnancy Complications - drug therapy; Pregnancy Outcome; Registries; Retrospective Studies; Valproic Acid - adverse effects; Valproic Acid - blood; Valproic Acid - therapeutic use
• ISSN: 0114-5916
• DOI: 10.2165/00002018-200629010-00001

Valproic acid (sodium valproate) is widely used as a first-line antiepileptic agent. As with many antiepileptic drugs, there are a number of consequences associated with the use of valproic acid in women of child-bearing potential. Most pregnancies have a favourable outcome in women with epilepsy, and these women should not be discouraged from becoming pregnant. Unlike many other antiepileptic drugs, valproic acid has no significant pharmacokinetic interactions with the steroid hormones used in oral contraceptives. During pregnancy, the major risks to mother and child result from loss of seizure control on the one hand, and an elevated risk of major congenital malformations due to antiepileptic drug treatment on the other. In particular, an elevated risk of major congenital malformations associated with valproic acid use has been a consistent finding in studies of patient registries and several large case series. In addition, developmental delay, characterised by low verbal IQ, has also been reported in children exposed to valproic acid in utero, although the relative risk is not precisely known. For these reasons, pregnancies in women being treated with valproic acid need to be planned, and the benefit-risk ratios associated with continuing valproic acid or changing treatment need to be discussed with the patient. When treatment with valproic acid is the most appropriate treatment to achieve optimal seizure control, a number of measures can be implemented to minimise risk to the fetus. These include the use of the lowest possible effective dose of valproic acid in monotherapy (ideally