Valproate and Foetal Anticonvulsant Syndrome

Philippa Whitford Excerpts

Thursday 19th October 2017 Commons Chamber

[Norman Lamb]

I thank the right hon. Gentleman for that, and he is right in what he says; I, too, feel that there is a sense of inertia. For goodness’ sake, for as long as women are not getting told about this, more such babies are being born. That is the awful horror of this.

[Dr Philippa Whitford (Central Ayrshire) (SNP)]

Many of us in the House have been approached by constituents or groups about several of these drug scandals, which represent a paternalistic time, when the patient was not part of a team in an open discussion with the doctor. I am sure there are many of these, so should they be looked at together, as the principles of them all are the same?

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[Paul Flynn (Newport West) (Lab)]

It was heartbreaking and infuriating to read the news that 68% of the women who are taking valproate today were not aware of the risks. That is a failure for all of us. We debated this issue in March 2013, and we have put down early-day motions. There was a television programme, chaired by Huw Edwards, in which the victims took part. We thought we had cracked it: we thought we had advertised enough so that no one, after 2013, could be in the position of not realising the terrible risks caused by taking valproate in pregnancy.

I am not making any criticism of anyone, except the MHRA, and we must look at our relationship with the regulatory body. The former Minister, the right hon. Member for North Norfolk (Norman Lamb), did all he could. He has a great and honourable record as a compassionate campaigner on many issues. It is a shock to all of us in that we did not expect there to be compensation, but it should now be coming along. It is not compensation in any serious way, but it is some admission that a terrible mistake has been made—not by the mothers, but by the system.

It is helpful to look back at what happened with thalidomide, which I remember vividly. There were 2,000 cases of birth defects in the United Kingdom; there were 20 in the United States. Why? The reason is that we went on prescribing Destobel for a year after the birth defects were suspected, because the drug company was adamant about it. It had tested the drug on animals, including pregnant animals—pregnant rabbits, even—and only when it went back to do another test of a particular strain of the drug on pregnant rabbits were the birth defects reproduced. That shows the limits of animal testing. The real difference was that the regulatory body in the United States would not accept thalidomide in that form, and its use produced a very small number of cases: 20 compared with 2,000.

We have had the effect of a drug called Vioxx for arthritis sufferers. According to the Food and Drug Administration in America, it caused 60,000 deaths; imagine it—60,000 deaths. How many bad reactions did the MHRA have in this country? About six. We would still be using it if the FDA had not discovered that death was one of the side effects of the drug, which was taken by millions.

GlaxoSmithKline in America has been fined—it is hard to believe—$3.5 billion. What was the fine for? It had suppressed the evidence of the trials it had carried out. It did not publish any of the negative results of the trials it carried out, and only the ones that were neutral or favourable. Drugs that were killing people were getting on to the market—this is a British company. What did the MHRA do in this country? Nothing! I wrote to them saying, “For goodness’ sake, you have to act against GlaxoSmithKline.” It is no coincidence that the person who chaired the regulatory body for more than a decade was a previous employee of that company. I am not saying that in this instance the body did absolutely nothing; it did produce the tools and provided advice, but that clearly did not work—how could it have done if 68% of the women still taking the drug did not know?

This issue applies to all Governments; it has been raised many times before. What we need is a regulatory body that is not paid for or controlled by the pharmaceutical industry but is independent and controlled nationally. Some years ago in Italy, the system changed. The pharmaceutical industry still pays for running the body, but for the past 20 years each Government have said that they would not have a fully independent body because they did not want to pay for it, although it was fine if the burden was taken by the pharmaceutical industry itself.

I do not want to say that we are all against the pharmaceutical industry, which has produced miraculous results this century. Valproate is a very good drug: everyone I have spoken to who has used it says that it is very effective and that it reduces seizures, epileptic fits and the incidence of bipolar disorders. We do not want to stop its use at all and we want to appreciate its quality, but after these four years, when the evidence from parents who have suffered has been there, clearly nothing has worked. We must look to reform our regulatory system, appreciating the value of the drug but at least setting up a fund that can express the sorrow of the country and the regret that we have not sorted this matter out or given warnings to future parents. We must make sure that the reforms suggested by the right hon. Member for North Norfolk proceed as a matter of great urgency.

[Dr Whitford]

Will the hon. Gentleman give way?

[Mr Deputy Speaker (Mr Lindsay Hoyle)]

He has finished.

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[Dr Whitford]

I come back to the point I made earlier. We seem to see these themes. Rather than having multiple separate inquiries, should we consider issues such as Primodos and valproate together? Common learnings need to come out of them.

[Mims Davies]

I absolutely agree. I hope to pull that issue together as I go on with my remarks. It is really important that we raise the case of sodium valproate, which, as we have heard, is still in use. All of these issues need to be looked at.

Common to this debate—and in all such cases, including Primodos—are the hidden, missing and lost documents, along with a delay in education and information. That was raised again today by the right hon. Member for North Norfolk. I pay tribute to Sky News for its exposés on valproate and Primodos, because this really matters to the families affected.

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[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?

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[Dr Philippa Whitford (Central Ayrshire) (SNP)]

I, too, pay tribute to the right hon. Member for North Norfolk (Norman Lamb) for securing this debate and trying to air this issue again. Epilepsy affects 1% of the population—600,000 people—and it is not a trivial condition. It is dangerous. As we have heard, 1,200 people a year die due to epilepsy, and we must not diminish that fact. At the lowest level, someone who has a fit after being well controlled suddenly cannot drive again, which can have quite a big impact, but at the other end of it there is death. We therefore must be careful not to send out a message that anti-epileptic drugs are bad, or even that Epilim is. It works really well, and it is one of the drugs that often can control the most dangerous seizure—the tonic-clonic or grand mal, as it used to be called—without the use of other drugs.

Almost all anti-epileptic drugs carry risk. Sodium valproate is the worst by far, but all the ones we have heard of in the past—phenytoin, phenobarbital, primidone and carbamazepine—carry some risk. We therefore have to recognise that it is not just as though the doctors prescribed the wrong drug. This condition is really hard to deal with, and we need people to have specialist input. We are really asking that from when girls reach puberty until they reach menopause or get into their 50s—when there is no risk of them having children—decisions are made with them by specialists.

As we have heard, there was obviously a recognition right back in the ’70s that sodium valproate could bring about congenital abnormalities, but what appears to have changed is the scale. If we look back, we see that people used to discuss a 2% risk of malformation and “some possibility” of developmental delay. We are now talking about 10% of children having a birth defect, which might be something like a minor cleft palate that can be dealt with, right through to spina bifida, meaning the child faces major physical disability. On a much worse scale, some 40%—almost half—of children face some form of developmental delay, which might mean an autistic spectrum disorder, learning difficulty or ADHD. That is a big change.

We heard earlier about the 1995 paper that started to bring these cases together. Before that, there were predominantly case reports—someone saying, “Oh, this is odd; I’ll write it up”—but we needed someone to bring things together. When we hear that 400 affected babies have been born in the year since the recent attempt to deal with this issue, we realise that had the yellow-card reporting system been working when we had perhaps 500, 600 or 700 cases a year, the situation would have been spotted much more quickly.

The system utterly failed to recognise a pattern and has to be reformed. If a woman gives birth to a child with a birth defect, or there is in the very early years recognition of some kind of major developmental delay, and she is on a drug, that should be reported, and I do not care what the drug is. Her GP may never have seen such a thing before and might not recognise that there could be an association, but someone sitting in the MHRA who is receiving 400 or 500 reports certainly ought to.

The obvious question is how to tackle this issue. The toolkit was put out in February 2016, because we have recently recognised the huge scale of the problem—the change is the recognition of the scale. It is therefore shocking and incredibly disappointing to hear that more than two thirds of women have not received any part of it. It is great that there is now some marking on packaging, but perhaps more of that needs to be combined, because we then do not have to depend on people remembering to hand something out or to pick something up. We would be empowering women to say, “Oh, what’s that? You’ve never talked to me about that,” and both sides would have the chance to have a discussion.

We have predominantly focused on the results of using sodium valproate during pregnancy but, as the hon. Member for—

[Norman Lamb]

Strangford.

[Dr Whitford]

Sorry. I am not doing very well today. Six hundred and fifty names is hard enough; adding another 650 constituencies just does my head in!

As the hon. Member for Strangford (Jim Shannon) mentioned, by the time a women is pregnant—crucially, by the time she knows she is pregnant—it is too late, because these abnormalities happen in the first trimester: those first two months when the brain and spinal cord are forming and the arches of the face are combining. That is why we particularly see neural tube defects, brain function abnormalities and cleft palate. Many women who lead hectic lives may already be two months pregnant by the time they finally know, and that means it is too late. That is why the annual review is important.

Epilim is perfectly fine for a girl to use if it gives good control for grand mal seizures, but we need to flag up the fact that when she is expected to be approaching puberty, discussions need to start with her and her family. Family planning is important for all women, but for women on these kinds of drugs, which must be stopped in pregnancy, it is crucial. We need to have that discussion so that the alternatives can be considered. I echo the comment that if a woman is pregnant and did not plan for that, she should not stop the drug on her own. She should have emergency access to a specialist who is able to look at her type of epilepsy and discuss the options with her, such as whether it would be safe to take nothing or if it would be better to change to something else. It should be recognised that uncontrolled seizures in pregnancy can cause the loss of the mother and the baby. We must not have any kind of irresponsibility by not flagging that up.

We had a debate in this Chamber last week on baby loss. It was a very powerful cross-party debate on the anguish that people face, whether it is due to early miscarriage, stillbirth or neonatal loss. We talked about that loss and bereavement, but any of us—male and female—who have had children know of the expectation and joy that comes from waiting for a child. There is still exactly that bereavement when we know that our child will face a life of physical and mental difficulties, and of learning disabilities. We know that a child with a marked learning disability has only a 7% chance of working. For the parents, there is the stress of knowing that there will come a point when they are not there, and of wondering how their child—perhaps now a young adult—will actually survive facing a harsh world.

Financial support is absolutely crucial to give families peace of mind. We need an inquiry, but rather than holding multiple inquiries, we should recognise that bringing some of these common themes together into one would be a much more powerful way to get people to understand that we are talking about relentlessly repeating patterns. Let us try to reform the things that allowed this to happen and to ensure that we support the families and the children to whom, sadly, it has happened.