Valproate and Foetal Anticonvulsant Syndrome

Liz McInnes Excerpts

Thursday 19th October 2017 Commons Chamber

[Liz McInnes (Heywood and Middleton) (Lab)]

I am pleased that we are having this important debate, and I pay tribute to the right hon. Member for North Norfolk (Norman Lamb) for securing it and for setting out so clearly the issues involved.

My career before I was elected was as an NHS clinical scientist. Working in a biochemistry laboratory, I was very familiar with sodium valproate as part of the battery of anticonvulsant drugs for which we regularly tested patients to help their clinicians better monitor their treatment and ensure that their dosage was at the optimum level. Until I met Emma Murphy, however, and became aware of her campaign, I was not aware of what appeared to be a systematic failure to inform women of the potentially damaging effects of taking valproate during pregnancy.

Only after watching a television programme about foetal anticonvulsant syndrome did Emma herself became aware that her own children’s health problems were probably attributable to the anti-epileptic drugs she had taken while pregnant, which had been prescribed to her from the age of 12. Like everyone in the House, I pay tribute to Emma Murphy and Janet Williams for their great campaigning work.

The damage to the developing foetus is thought to be caused in the first trimester of pregnancy when the anti-epileptic drug crosses the placenta into the foetus, and the effects depend upon the dosage and the drug. Sodium valproate, or Epilim, is indicated in 80% of cases of foetal anticonvulsant syndrome. Experts such as Dr Peter Turnpenny, clinical geneticist at the Royal Devon and Exeter Hospital, say that Epilim may affect about 560 babies every year. He adds:

“About 10% of foetuses exposed to sodium valproate will have a major congenital malformation such as cleft palate. 12% are likely to be diagnosed with a neurodevelopmental disorder.”

Reports linking valproate to birth defects started to appear, most notably, in 1981, with a paper by H. Nau entitled “Valproic Acid and its Metabolites”. In 1983, the British Medical Journal published an article in which the Royal Liverpool Hospital cited two cases suggesting a link between birth defects and valproate taken during pregnancy. The American Journal of Medical Genetics cited seven cases in 1984 of children born with malformations to mothers taking valproate, and the Journal of Paediatrics cited 26 cases in 1986. The list goes on. It would appear that the evidence was steadily building up with the publication of more and more cases linking valproate to birth defects. The Committee on Safety of Medicines and the Medicines and Healthcare Products Regulatory Agency noted those reports, and, I hope, monitored the use of valproate, particularly during pregnancy.

[Dr Whitford]

We have heard about various scandals. In the case of Vioxx, which was mentioned by the hon. Member for Newport West (Paul Flynn), trials did not show a problem but real-world use did. Does the hon. Lady think that we need some kind of reform of the reporting system? There is something that we call a yellow card, and patients can now fill it in themselves, but many of them do not realise that. I feel that there is not enough “flagging up” when patients suspect that they are suffering from side-effects.

[Liz McInnes]

The hon. Lady is absolutely right. She and I are well aware of the yellow card system, because we have both worked in the NHS, but how many people out there know that they can report side-effects of drugs, or even suspected side-effects? We really have a job to do in conveying that message to the general public, and we also need people to collate the information and act on it.

A definitive paper stating that there was a clear link between valproate taken during pregnancy and birth defects was published in 1995. It was entitled “Foetal Valproate Syndrome”, and was written by geneticists at St Mary’s Hospital, Manchester. It is clear that the evidence has been building up for a long time, so why does it appear that women were not warned about the potential dangers of taking the drug in pregnancy?

[Fiona Bruce]

That 1995 report concluded that the “risk” of foetal valproate syndrome when babies were exposed to valproate was “significant”.

[Liz McInnes]

That was probably the first research paper to suggest that it was not just coincidence and that there was a causal relationship, which is why it is seen as definitive.

The pharmaceutical company Sanofi, which many Members have mentioned, has stated that it has kept in line with scientific knowledge when reporting side-effects in a foetus. However, from as early as 1983 the CSM and the MHRA reported the problems caused by taking sodium valproate in pregnancy, but did not insist that Sanofi issue warnings in the form of a patient information leaflet.

Even now, to this day, epilepsy charities report that women are not aware of the potential risks when taking the drug in pregnancy. A survey has shown—I know it has already been mentioned, but it does no harm to reinforce these findings—that 18% of women taking sodium valproate were not aware of the risks during pregnancy, and 28% said that they had not been informed of any risks. That is despite the production by the MHRA of a valproate toolkit designed to help healthcare professionals to talk to women with epilepsy about the risks of taking valproate during pregnancy.

[Norman Lamb]

The hon. Lady is making an incredibly valuable contribution to the debate. Does she agree that if it is clear during a period of time that the amount of a drug that is being prescribed is significantly more than the guidance suggests is appropriate, it is not acceptable for the drug company, the regulator and the Government simply to be passive and to allow that to continue? If we knew that this drug was being over-prescribed, which appears to be the case, why on earth was action not taken?

[Liz McInnes]

That is a very good point, and if we manage to establish an inquiry, it should look into the issue of over-prescribing.

I want to mention other agencies. The European Medicines Agency has also recommended a strengthening of measures to reduce the risk of harm to babies born to mothers taking valproate. Information from the House of Commons Library outlines a situation in France, which has already been referred to, with an estimate that between 425 and 450 children were affected by birth defects attributable to valproate from 2006 to 2014. The French Parliament this year voted to set aside €10 million for claims related to valproate. The Health Minister, Marisol Touraine, described this as a “starting point” and stated that compensation would ultimately be paid by those deemed responsible:

“I regret that Sanofi didn’t seek an amicable settlement as a matter of principle. I hope Sanofi will change its position.”

Sanofi had no comment to make on the Minister’s remark. A class action has also been brought by the French association for people affected by sodium valproate against Sanofi.

In the UK, in 2004 a class action was brought by a group of families under the Consumer Protection Act 1987, which was expected to go to trial in 2011, but the litigation was discontinued prior to this after the Legal Services Commission withdrew funding. It is disappointing that this Government have said that there are no current plans to introduce a compensation fund similar to that in France, and I urge them to reconsider.

I fully support the remedial steps outlined in the motion, including the call for an inquiry, and this Government must bring forward a care plan and financial assistance for the victims of this national scandal.