Prenatal valproate exposure and brains

The paper by Amanda Wood and colleagues [1] (open-access) makes a potentially very important contribution to the growing literature looking at how prenatal exposure to sodium valproate (VPA) may affect some children. Authors reported on: "regional structural cortical brain changes in humans exposed to VPA in utero" and specifically, increased cortical thickness in the left inferior frontal gyrus.

Lightning and lava @ Oliver Spalt @ Wikipedia 

In case you need any background on the story behind pregnancy exposure to VPA, I would direct you to a few previous posts where the topic has been covered on this blog (see here and see here) with an autism slant. You might also read my small contribution to a more formal article on this topic here.

Outside of any reported elevated risk of offspring autism or autistic traits associated with prenatal VPA exposure, I'm also minded to bring in some interesting work on intestinal inflammation being reported in a VPA mouse model (see here) to further highlight that important gut-brain axis which I seem to be a little obsessed with.

The Wood paper is open-access and has some accompanying media coverage but a few pointers might be useful...

• Following other work by the authors on this topic [2] the idea behind this latest research was to apply the science of neuroimaging to a participant group comprising 16 children exposed to VPA in-utero compared with age- and sex-matched children not exposed to such pharmaceutics prenatally.
• MRI scans were taken and analysed and "whole brain group differences" assessed. 
• Results: well, as discussed, there were some findings in terms of cortical thickness but also specifically with language skills in mind. To quote again: "Asymmetry of cortical thickness in the inferior frontal lobes was seen in controls but not cases". I understand that this finding might have some relevance to language processing [3] although set my non-expert stall out on such matters. As per that previous link [2] and other evidence [4], language functions in VPA exposed children tend to poorer compared to controls and to those exposed to other anti-convulsant medication during the nine months that made us. This last point on different medications potentially carrying different risk profiles [5] is something equally interesting.

Allowing for the relatively small participant groups studied and the lack of any other research parameter such as looking at accompanying brain chemistry which may be important [6], the Wood paper offers some intriguing insights into how pregnancy VPA use might affect infant brain development. The very important detail of analysis being based on real human children and not rat offspring also invites some further examination of previous results based on rodents [7]. Rats are rats, children are children.

I'm going to leave you with a quote from the authors about their study: "VPA remains an important medication for people with epilepsy. What this study really tells us is that further research is required so that all women with epilepsy can make informed decisions about their medication use during pregnancy". I couldn't agree more, and as per the Treating for Two initiative, I'm not the only one.

Music then... HRH Gaga and Just Dance.

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[1] Wood AG. et al. Altered cortical thickness following prenatal sodium valproate exposure. Annals of Clinical and Translational Neurology. 2014. July 3. doi: 10.1002/acn3.74

[2] Nadebaum C. et al. Language skills of school-aged children prenatally exposed to antiepileptic drugs. Neurology. 2011 Feb 22;76(8):719-26.

[3] Powell HWR. et al. Hemispheric asymmetries in language-related pathways: A combined functional MRI and tractography study. NeuroImage. 2006; 32: 388-399.

[4] Shallcross R. et al. In utero exposure to levetiracetam vs valproate: development and language at 3 years of age. Neurology. 2014 Jan 21;82(3):213-21.

[5] Vajda FJE. et al. The teratogenicity of the newer antiepileptic drugs – an update. Acta Neurol Scand. 2014. July 18

[6] Almeida LE. et al. Increased BDNF expression in fetal brain in the valproic acid model of autism. Mol Cell Neurosci. 2014 Mar;59:57-62.

[7] Mychasiuk R. et al. Effects of rat prenatal exposure to valproic acid on behaviour and neuro-anatomy. Dev Neurosci. 2012;34(2-3):268-76.

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Wood, A., Chen, J., Barton, S., Nadebaum, C., Anderson, V., Catroppa, C., Reutens, D., O'Brien, T., & Vajda, F. (2014). Altered cortical thickness following prenatal sodium valproate exposure Annals of Clinical and Translational Neurology DOI: 10.1002/acn3.74