On the question of valproate use and pregnancy

I very much want to stress the point that 'no medical or clinical advice is given or intended' on this blog before proceeding further with discussions based on the commentary paper by Richard Balon & Michelle Riba titled: 'Should Women of Childbearing Potential Be Prescribed Valproate?' [1].

Valproate, as in preparations like sodium valproate, has been a particular talking point in recent years as a consequence of something of an emerging body of peer-reviewed science suggesting that its use during pregnancy may place offspring at some elevated risk for various neurodevelopmental outcomes (see here). The Medicines and Healthcare Products Regulatory Agency (MHRA) here in Blighty issued some revised guidance last year (2015) 'strengthening' warnings about the use of valproate under certain circumstances. This follows some research history on how for example, a valproic acid mouse model of autism has been used as "environmentally induced ASD [autism spectrum disorder] models in rodents" [2] for quite a few years.

Balon & Riba cover various points in the debate about valproate use during pregnancy specifically focused on the known "teratogenic outcome[s]" that have been reported down the years bearing in mind that valproate serves an important (sometimes life-saving) use. I was particularly struck by the 'interference' with folic acid metabolism discussed in their commentary on the basis of some science in this area [3]. With that pinch of salt at the ready, some readers might already know that folate metabolism has some research history in autism circles (albeit not necessarily settled science) and indeed, continues to make scientific waves. Accepting that valproate might have more than one action when potential offspring outcomes are concerned (see here), I do wonder if further research focus could be directed on the folate aspect of the drug when it comes to risk of various neurodevelopmental diagnoses for example?

The question of valproate use outside of the management of epilepsy is a focus of the Balon/Riba article; specifically "used in acute mania or in prophylaxis of bipolar disorder." Bearing in mind that various other medicines are available to manage these conditions and that "unplanned pregnancies are common in this population" [4] I don't think it's out of place for the authors to "recommend that the FDA and valproate manufacturers declare valproate contraindicated in women of childbearing age and issue guidelines for counseling women of childbearing potential with bipolar disorder." Indeed, NICE here in England, seem to have taken a lead on this...

If in doubt, please consult with your medical physician.

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[1] Balon R. & Riba M. Should Women of Childbearing Potential Be Prescribed Valproate? J Clin Psychiatry. 2016; 77: 525–526.

[2] Ergaz Z. et al. Genetic and non-genetic animal models for Autism Spectrum Disorders (ASD). Reprod Toxicol. 2016 Apr 30. pii: S0890-6238(16)30077-6.

[3] Fathe K. et al. Brief report novel mechanism for valproate-induced teratogenicity. Birth Defects Res A Clin Mol Teratol. 2014 Aug;100(8):592-7.

[4] Marengo E. et al. Unplanned pregnancies and reproductive health among women with bipolar disorder. J Affect Disord. 2015 Jun 1;178:201-5.

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Balon R, & Riba M (2016). Should women of childbearing potential be prescribed valproate? a call to action. The Journal of clinical psychiatry, 77 (4), 525-6 PMID: 27137420