Potential risk of neurodevelopmental disorders in children born to men treated with valproate
- study evidence suggests there may be an increased risk of neurodevelopmental disorders in children born to men taking valproate in the 3 months before conception (1):
- a retrospective observational study (EUPAS34201) used data from multiple registry databases in Denmark, Norway and Sweden and focused on birth outcomes in children born to men who were taking valproate or taking lamotrigine or levetiracetam (other medicines to treat conditions similar to those treated with valproate) around the time of conception
- data showed that around 5 out of 100 children had a neurodevelopmental disorder when born to fathers treated with valproate compared with around 3 out of 100 when born to fathers treated with lamotrigine or levetiracetam
The EMA states that it is recommended that valproate treatment in male patients is initiated and supervised by a specialist in the management of epilepsy, bipolar disorder or migraine (1).
UK guidance states (2):
Information for healthcare professionals (2):
- findings from a retrospective observational study, combining analyses of electronic medical records in Norway, Denmark and Sweden, indicate a possible increased risk of neurodevelopmental disorders in children born to men treated with valproate in the 3 months prior to conception, compared to those born to men treated with lamotrigine or levetiracetam
- in the study, the cumulative risk of neurodevelopmental disorders ranged from 4.0% to 5.6% in the valproate treated group versus 2.3% to 3.2% in the composite lamotrigine/levetiracetam monotherapy treated group (pooled adjusted hazard ratio 1.50, 95% CI 1.09 to 2.07)
- this potential risk is much lower than the up to 30-40% risk of neurodevelopmental disorders in children born to mothers taking valproate during pregnancy, estimated from several studies
- the study did not include an untreated group and background risk in this patient population is therefore unknown
- an increased risk of neurodevelopmental disorders in children of fathers treated with valproate in the 3 months prior to conception is possible however the causal role of valproate is not confirmed. As such this advice is precautionary
Advice for healthcare professionals (2):
- inform male patients (of any age) who may father children of the possible risk at initiation of valproate or at their next regular treatment review – this counselling should be given irrespective of the indication for valproate and also after intravenous use of valproate
- as a precaution, recommend that male patients use effective contraception (condoms, plus contraception used by the female sexual partner) throughout the valproate treatment period and for 3 months after stopping valproate, to allow for one completed sperm cycle not exposed to valproate
- at the next regular treatment review, discuss with men on oral valproate treatment whether they are planning a family in the next year and if they are, refer to a specialist to discuss alternative treatment options
- if a female patient reports they are pregnant or planning a pregnancy with a man on valproate (including those undergoing IVF), refer for prenatal counselling
- advise men not to donate sperm during valproate treatment and for 3 months after stopping valproate
- report any suspected adverse drug reactions associated with valproate on a Yellow Card
For more information then see (1,2).
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