Anticonvulsant valproic acid increases risk of congenital disorders

Taking the anticonvulsant valproic acid in the early stages of pregnancy not only increases the risk of spina bifida but also of other congenital disorders. This risk is also higher than that of other anticonvulsants. This should be considered when choosing an anticonvulsant for women who perhaps would like to have children, at present or in the future,
according to researchers of the Pharmacoepidemiology and Pharmacoeconomics department of the University of Groningen and the University of Ulster in an article published in the New England Journal of Medicine on 10 June 2010.

The Groningen researchers have been involved for years in the EUROCAT network for the registration of congenital disorders. The ‘EUROCAT Antiepileptic Study Database’ was used in the valproic acid study. The pregnancies described in this database – the largest ever used for such a study – are from registrations of congenital disorders in fourteen European countries. In the period covered by the study, four million pregnancies and 100,000 children with a congenital disorder were recorded.

Spina bifida

Research done in Groningen showed that ASD (a hole between the left and right heart chambers), a cleft palate, hypospadias, polydactyly (an extra finger or toe), craniosynostosis (premature fusion of skull sutures) and limb defects occur 2-7 times more often with women using valproic acid in the first three months of pregnancy than with women not using it.
The risk of spina bifida – which was already known – proved to be 12-16 times higher than in women not using anticonvulsants.

Keep using it

To quit using anticonvulsants is not an option for women with epilepsy as the risk of epileptic fits increases with all the related dangers. Despite the increased risk for the congenital disorders that were identified, a sizeable majority of children are born without defects. Women who need valproic acid should not stop using it.

Alternative anticonvulsants

In a direct comparison with other anticonvulsants, valproic acid proves to give a higher risk of all the congenital disorders mentioned earlier except for cranisynostosis. However, it is difficult to switch medication just before pregnancy as it takes time for the patient to adjust to the new drug. Researchers feel that when choosing medication for women who may in future want to have children it would be wise to consider the risk of congenital disorders.

Statistically relevant

Studies on valproic acid and the related risk of congenital disorders have often been published in scientific journals but ar usually too small to draw statistically relevant conclusions. This is because the prevalence of epilepsy (and thus the use of anticonvulsants) among pregnant women is low and also because most children are born without congenital disorders when valproic acid is used.  EUROCAT’s extensive database is large enough to determine the risks.

Chronic illness

Women with epilepsy or some other chronic disease and those treating them need to know about the safety of medication used during pregnancy. A number of new anticonvulsants have been put on the market in recent years which shall be evaluated in future. Research into the consequences of medication for pregnant women with epilepsy or another chronic disease received an important stimulus when EUROCAT was awarded a grant for the EUROmediCAT project under the European FP7 programme.

Note for the press

More information: Prof. Lolkje de Jong, tel. 050 – 363 3330/7576; l.t.w.de.jong-van.den.berg rug.nl or Janneke Jentink MSc (first author), tel. 050 - 363 2476; j.jentink rug.nl); Farmacoepidemiology and Farmacoeconomics department, University of Groningen