Sodium Valproate

Pregnant-woman-1024x680

Sodium Valproate has been on the Market and prescribed in the UK since 1973, with the Teratogenic effects (effects on foetus during pregnancy) noted by the UK Government at the time and the drug company in 1974.

valproate picture

“On the evidence before them the Sub-Committee recommended variation of the product licence to delete the ‘requirement regarding monitoring on the condition that the indication for use reads as follows”
“for use in generalised, focal or other epilepsy but only to be used in severe or resistant cases in women of child bearing age.
And that the following warnings is included in all literature issued about this product”
“Women of Child Bearing Age
This compound has been shown to be teratogenic in animals. Any benefit which may be expected from its use should be weighed against the hazard suggested by these findings”
Somethings which was only reported to the public following the European Review on Valproate in 2014/2015 following the request for a review by INFACT.
Over the years, through research we know that Valproate causes numerous problems for the fetus and to varying degrees:

Valproate Complications for Baby:

Unusual (Dysmorphic) facial features

facial features

Developmental problems:
Speech & Languages developmental
Low Verbal IQ
Hearing
Vision
Fine & Gross Motor Control
Hypotonia
Short term Memory
Inguial Hernia
Autism
ADHD
Aspergers Syndrome
Dyspraxia

In Boys:
Hypospadia
Undescended Testes

Major Malformations

Gastroesophageal Reflux
Bowel & Bladder
Kidney Malformations
Heart Malformations
Cleft Lip/Palate
Spina Bifida & Rib Fusion
Radial Short or absent radius in the arm
Talipes
Polydactyly (Extra) fingers and/or toes
Clinodactyly (Curvature of) fingers and/or toes
Craniostenosis

Since 2013 there have been a number of research papers which have stated the relation between Valproate in pregnancy and all the above disabilities:

• The Prevalence of Neurodevelopmental Disorders in Chidlren Prenatally Exposed to Antiepileptic Drugs: Rebecca Bromley et al. J Neurol, Neurosurg Psychiatry 2013; 0: 1-7

Exposure to Valpraote in Pregnancy Figures :

Approximation Figures:
These figures have been calculated using the Summary of Live Birth Statistics from the Office of National Statistics (ONS) for England and Wales from 1996 – 2011 and the Man et al paper ‘Antiepileptic Drugs during Pregnancy in Primary Care: A UK Population Based Study’ (2012)
The figures from the documents together show the year, number of births for each year and the percentage of pregnancies where Valproate was taken. The calculations show that:

Column 1 = Year
Column 2 = ONS Births in this year
Column 3 = % of births where Valproate taken
Column 4 = Number of babies exposed to Valproate

1996649.4850.1%649
1997643,0950.25%1607
1998635,9010.2%1271
1999621,8720.2%1243
2000604,4410.2%1208
2001594,6340.1%594
2002596,1220.15%894
2003621,4690.1%621
2004639,7210.1%639
2005645,8350.1%645
2006669,5310.05%334
2007690,0130.1%690
2008708,7110.1%708
2009706,2840.1%706
2010723,9130.1%723
2011723,1650.1%723

Therefore between 1996 – 2011 the approximate number of babies born to women taking Sodium Valproate is 12,047.

It has been noted that approx 40% of those exposed to Valproate in pregnancy with have significant cognitive and/or physical disabilities. (Bromley et al 2013, Meador et al, 2013)
Scientific data demonstrates that 11% of children exposed to Valproate in pregnancy will be born with a major congenital malformation (Bromley et al 2013, 2014, Cochrane Review)
Applying these figures 4,818 of the 12,047 exposed children between 1996 – 2011 are likely to have been significantly affected in some way with Neurodevelopmental problems, reduced life changes, long term employment and care issues, and a heath/educational/social care cost to the tax payer.

Bearing in mind that Valproate has been licenced since 1973.

In the recent journal papers Bromley et al 2013, 2014, Man et al: 2012 and the Cochrane Review we know that 40% of those exposed to Valproate in pregnancy are affected by neurodevelopmental problems such as Autism etc.. with a further 11% affected by Major Malformations such as Spina Bifida, Cleft Lip/Palate, Kidney & Heart Malformations. That’s 51% actually affected by Valproate when taken in pregnancy. The question is:

Is this an acceptable risk?

Minister for Life Sciences Statement taken from
Clinical Practice Research Datalink covering only 7-8% of the population:

• It has recently been reported that between 30,000 – 40,000 women become pregnant every year in the UK between the ages of 14-45yrs old.
• Only (0.08%) are prescribed Valproate.

When calculated into General Population figures this means:
• 336 babies are exposed to Valproate every year
• 175 actually affected by Valproate every year
• Around 28 babies per month are exposed to Valproate
• Around 14 per month are harmed by Valproate.
• Since Valproate came onto the Market in the UK in 1973, around 14,448 have been exposed to the drug in pregnancy
• 7,386 have been affected by Valproate since 1973.

This drug is still prescribed today due to its useful effects on Epilepsy, yet it is now also prescribed for Bipolar and off-label for Migraine and as a pain relief drug.

It is important that the New Valproate Toolkit, released on the 8th February 2016 is used to its full potential alongside the Patient cards given at the pharmacist on collection of a Valproate prescription.

https://www.gov.uk/government/publications/toolkit-on-the-risks-of-valproate-medicines-in-female-patients

In June-July we are aware that the Sanofi boxes for Valproate and its Patient Information Leaflets are to change with the warning also being shown on the outside of the box.
The questions are:
• How many women actually received the Purple Sanofi box when they collected their last prescription.
• How many women received a Patient Information Leaflet with the white box.

We hope all topics have been covered on this page, if you have any questions please contact INFACT/FACSA and we’ll help all we can.

Supporting Evidence (Journal Papers)

The Prevalence of Neuro Developmental Disorders of children exposed to Anti Epilepsy Drugs http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115188/ – The prevalence of neurodevelopmental disorders in children prenatally exposed to antiepileptic drugs

Does Folic Acid use decrease the risk for Spina Bifida ? http://www.ncbi.nlm.nih.gov/pubmed/20680999 – Does folic acid use decrease the risk for spina bifida after in utero exposure to valproic acid?

Folic Acid Use and Major Congenital Malformations in children of women with Epilepsy http://www.ncbi.nlm.nih.gov/pubmed/18977812 – Folic acid use and major congenital malformations in offspring of women with epilepsy: a prospective study from the UK Epilepsy and Pregnancy Register.