Our lovely colleague in New Zealand Denise Astill, has finally hit the media about the topic of FACS. She has taken her families story to the media and it has finally been acknowledged. Well done Denise, INFACT & FACSA are so proud of you, showing that a mothers love is everything in an industry where speaking up against Health Professionals is frowned upon
Any mother would be shocked to discover her children were disabled. For Denise Astill, it was not just shock but also guilt.
When her twin daughters, Jazmyn and Natasha, were diagnosed with foetal valproate syndrome (FVS) at the age of four, she discovered the likely cause was a drug she had taken during pregnancy. “I was in tears for days and days after the diagnosis and couldn’t believe that I had done this to my daughters. After everything we had been through to conceive them – and then this happens.”
Epilim is an anti-epilepsy drug manufactured by pharmaceuticals giant Sanofi.
Since the emergence of new research in 2009, Ministry of Health regulator MedSafe has published a warning on its website: “Like most medicines of this kind, Epilim may affect your developing baby if taken in the first trimester of pregnancy, as it is suspected of causing an increased risk of malformations in the exposed foetus. Also, children born to mothers who take Epilim throughout their pregnancy may be at risk of impaired cognitive development or withdrawal syndrome.”
But even before 2009, there was clear evidence of the drug’s dangers – evidence that parents say was not passed on to young women considering starting families.
Denise and her husband, Cameron, adore Jazmyn and Natasha but wish they had been told more about the risk of having babies with birth defects caused by Epilim. The girls have developmental and physical problems and will need support for the rest of their lives.
Sodium valproate – trade name Epilim – is an anti-epileptic drug also used for other conditions such as bipolar disorder, pain and migraines.
It has been compared to thalidomide after studies showed women on high doses have around a 20 per cent chance of having a baby with a range of defects such as different-looking facial features, neurodevelopmental delays including autism, a lower IQ and physical disabilities. These defects are recognised clinically as FVS.
The figures come from the Australian Pregnancy Register (New Zealand has no formal register) and its data shows 6 per cent of women on a low dose will have a baby with birth defects. The risk increases to 50 per cent in a woman taking Epilim if she already has a child with birth defects.
The syndrome is causing so much concern worldwide that the European Medicines Agency is reviewing all data on the benefits versus risks of using Epilim in pregnant women.
The responsibility to inform women about these potential birth defects lies with the doctor who prescribes it, but there is concern that women who have been taking the medication long-term may not have been told of the risk when younger, or have not fully understood the seriousness of the warning. There’s also a fear that some doctors are not emphasising enough the potentially lifelong effects of Epilim on foetuses.
Now, medical specialists and some parents of children who have the syndrome are urging health authorities to put blunt warnings on all the packets, and include a brief and easy-to-read patient information sheet.
An estimated 8000 women of child-bearing age are taking medication for epilepsy in New Zealand, and others for different reasons.
Since 2005, ACC has accepted 11 FVS claims for children younger than four years old because it is considered a treatment injury and so far has cost more than $1 million to treat. These children will be under ACC care for the rest of their lives. It’s likely more people are receiving ACC support for this syndrome, but before 2005 it was categorised under medical misadventure and was not recognised as FVS so the figures are not available.
The number of ACC claims for this syndrome is expected to increase as more cases are diagnosed, says Denise Astill. “I regularly hear of new babies with symptoms and it shouldn’t be happening. These pregnant women aren’t being fully informed and something needs to change.”
UK parents took legal action against Sanofi, on behalf of more than 100 children whose mothers allege they suffered birth defects because the drug was taken during pregnancy.
The case was publicly funded by legal aid through the Legal Services Commission, and the lawyers claimed they had evidence proving Sanofi was responsible for the injuries, and was liable for compensation. Claimants alleged that if Sanofi had adequately warned them about the drug’s risks, they would have chosen other treatment options.
But public legal aid funding was withdrawn on the grounds it was available only in a small number of personal injury cases and, as a result, the claimants had to withdraw their case.
In the United States, Epilim is sold under the brand name Depakote. There, the drug company Abbott Laboratories paid more than US$1 billion ($1.27b) to settle the charges of alleged illegal marketing of Depakote to paediatric and geriatric patients. The company is now facing hundreds of personal injury lawsuits filed by families who have had a child born with birth defects after Depakote use during pregnancy.
Astill was a teenager when she was diagnosed with epilepsy. In her mid-20s she went through IVF to conceive children. Before getting pregnant, Astill says she asked her neurologist whether the medication could affect unborn babies. “The neurologist said it could cause neural tube defects or spina-bifida but taking more folic acid would counteract that.”
He told her that not taking the medication during pregnancy could result in a seizure, which could reduce the flow of oxygen to her babies through the umbilical cord, so she thought staying on Epilim was the safest option since no other type of medication was offered. “We then went to see a maternal medicine specialist and he said the same thing – so we thought, two specialists can’t get it wrong. How wrong we all were.”
Astill did not have any seizures during her pregnancy but had high blood pressure and the twins were born six weeks early. “There were questions early on as they were slow to walk and talk, had socialising difficulties as well as eyesight and hearing problems. It wasn’t until the girls were four that we had their diagnosis confirmed by a geneticist – that they both have foetal valproate syndrome, but different characteristics of it.”
Natasha has autistic traits such as needing to stick to a routine, being frightened of loud noises and struggling to make eye contact. “She has a wide nose that doesn’t have a bridge and a bigger forehead and thin upper lip. Natasha also has a rare heart murmur as it is on both sides of her heart. She has had surgery on six of her toes for what is called ‘hammer toe’ so they needed to be released to sit naturally. Natasha also has other characteristics of FVS and will need assistance to be able to live independently when she is older.”
Jazmyn has more physical disabilities such as low muscle tone and co-ordination problems, says her mother. “Meanwhile, they both have learning difficulties and are missing some teeth, and the list goes on.”
She believes their disabilities could have been avoided, and wants to prevent it happening to others. “It has a huge impact on our lives. I had to totally change my life and of course there are ongoing medical appointments. I think the girls have enriched my life but their ‘normal’ is a different sort of normal.”
Last year Astill complained to the health and disability commissioner about the advice she received from her specialists and asked for warnings to be put on the packets. However, her complaint was turned down.
The commissioner ruled that she had been fully informed of the significant risks of more seizures if she changed her medication, and the final decision about what anti-epileptic drugs to take during her pregnancy was up to her. In a letter to Astill, deputy commissioner Theo Baker said she was sympathetic but the information provided to Astill was adequate.
Astill is now setting up a charity called Foetal Anti Convulsant Syndrome NZ, focusing on support, education, awareness and prevention.
She’s calling for a patient information sheet to be put in every box of Epilim and a warning on the outside, and for more information about the high risk of birth defects to be provided to prescribers of Epilim.
“That could be through education sessions by the pharmaceutical company that manufactures it, Sanofi,” she says.
“Despite the specialists saying I was aware of the risks . . . I was not.”
Astill does not understand why health authorities are not more proactive about a syndrome which causes disabilities that are debilitating and often expensive to care for. “I believe it has caused more birth defects in New Zealand than thalidomide and that there are many people with disabilities caused by Epilim, but aren’t aware that’s the reason.”
Astill’s story is not an isolated one. Tanya McLaren and her husband, Rodney, live in Oamaru with their two children. Tanya also has epilepsy and, after conception issues, they adopted their son nine years ago, who has developmental problems. “Because of that we were extremely focused on doing all we could to make sure that any future child would be as healthy as possible, and started our IVF journey.”
Four-and-a-half years ago their daughter, Mia, was born and has since been diagnosed with FVS. “She is on the autistic scale, has dysmorphic facial features such as a thin upper lip, eyes that look a little like Down syndrome, a broad forehead and a small chin.
“Mia’s developmental milestones have all been delayed – not learning to walk until she was about two and she has just learnt to run this year.”
Mia also has a heart murmur and respiratory problems such as struggling to get rid of phlegm in her chest. “She picks up every cold and bug that’s going around. Mia has regular meltdowns, and floppy joints along with quite a bit of pain.”
Tanya says she no longer trusts most doctors. When they were about to start IVF the couple went to a neurologist and asked about pregnancy and the Epilim she was taking. “We were warned that when pregnant my seizures may increase but that I can use meds to control it. He said Epilim was quite safe as long as you increase your folic acid. He did mention there was a chance of spina-bifida or cleft palate being the worst-case scenario, but said the folic acid would negate that. He said there was a 1 to 2 per cent chance of our child having a birth defect.
“We always knew if I went off the meds there would be more danger to the child. But I wasn’t given the choice to change medication. We just remember thinking ‘if I take folic acid everything should be fine’.”
ACC has accepted Mia’s claim and now provides a physiotherapist, occupational therapist, speech therapist and behavioural psychologist to support her. Her mum believes there are more children with this syndrome than health authorities realise. “There is another case here in town that hasn’t been diagnosed yet. The mother with epilepsy has three children with symptoms, and I know of another mum who has a teenage boy with autism.
“I was never told about potential birth defects with Epilim and I have been taking it for years. If they think they are informing women in their reproductive years – they are not.”
Dr Elizabeth Walker, an Auckland neurologist who specialises in epilepsy, says a relatively small number of women are on Epilim. It is preferable to start on an alternative drug, Walker says, but some women have a certain type of epilepsy that only Epilim can control.
Medication changes can often be made before considering pregnancy to minimise the risk, she adds. “The risk of a major foetal malformation is increased for all anti-convulsant agents. It is only within the last decade that enough statistical data about the higher risk of FVS has been collected. I now don’t know of anyone who would prescribe a high dose of Epilim to a pregnant woman.”
However, she says, sometimes women are stuck between a rock and a hard place. “I do still prescribe it reluctantly to women after discussing it and trying all other appropriate medications.”
So what about women who did seek advice but say they weren’t fully informed about potential birth defects? Walker says some may be falling through the cracks: “The GP may not have had time to go through the risks if they prescribe it. The paediatrician who originally prescribed the drug may have done it when [the patient was] young so didn’t discuss birth defects, and for maternal doctors, there could be the presumption that another doctor has already told them. The patient may have got ‘lost’ between doctors.”
Despite this, Walker is sceptical about warnings on packets, saying it may lead to women suddenly stopping their medication without consulting a doctor. “Patients can die from uncontrolled epilepsy.”
Dunedin-based anaesthetist Dr David Jones, who has prescribed Epilim to dozens of patients for neuropathic pain, is one of the specialists who does believe more direct warnings may help.
“If a woman was in the child-bearing age range they were always warned about the potential for birth defects and it is definitely a prescriber’s responsibility to do so. They must be made aware.”
Jones says it is sometimes difficult to know if the patients have really listened. “I think it would be extremely useful to have some sort of warning printed on every drug packet as studies have shown that patients take in less than one-third of the information we may talk about with them. Giving them a brief and easy-to-read information sheet could also be beneficial but I am sceptical about whether every patient would have a look. I think the current information provided in many medication packets is in such small print and so detailed that it is useless.”
He wouldn’t oppose such large and blunt warnings as those on cigarette packets. “Having the message constantly in the person’s face would be better than one warning from a specialist.”
Jones chooses not to prescribe Epilim any more for two reasons – there are better neuropathic pain medicines available, and because of the risk of birth defects. “I’m fortunate to now have the luxury of using other effective drugs for pain relief whereas for some people who have epilepsy, this may be the only medication that helps control their seizures.”
MedSafe believes the risks around Epilim are being adequately managed – that women of child-bearing age are being given the information they need to make an informed decision.
MedSafe group manager Dr Stewart Jessamine says: “Epilim has been available here since 1975 and we have been informed of only about 13 cases of congenital abnormalities. As far as we are aware doctors are communicating the risks to their patients. It’s not perfect but it appears to be working.”
Jessamine says well established advice has been given to women about this drug for many years. “If we are not getting a lot of reports to the contrary, then we have to believe the risk is being managed appropriately for women of child-bearing age. We will take reports from specialists, GPs and even families about it.”
He says information is available on the MedSafe website. “In New Zealand the data sheet for Epilim says women who are pregnant or thinking of becoming pregnant should not use Epilim and consult with their specialist as there are risks about changing epilepsy medication. There is also an obligation on doctors to fully inform patients.”
If someone is on a medicine long-term, he says, it’s reasonable to expect there is regular discussion between the doctor and patient. If something in their situation changes, such as becoming pregnant, further advice should be given.
Under the existing Medicines Act, says Jessamine, there’s no requirement for a warning or an information sheet to be included in every medicine packet but that may change. “In the future they may be included in the pack, or there could be a website link on the medicine pack, or the pharmacist can provide it. We will need to find out what is the most effective way to share the drug information. No system is absolutely foolproof and we are not seeing data that is telling us to change what is currently happening.”
Retiring Health Minister Tony Ryall was asked if patient information could be inserted into medication packets, as is required in many countries. In a letter back, he said there was no legislation requiring it. However, he added, the Australian and New Zealand Governments are currently establishing a single therapeutic goods regulatory authority for both countries and under that, patient information will have to be provided with all prescription medicine.
As for Sanofi, the drug company says its data and leaflets for Epilim have been recently reviewed.
Alan Carter, the company’s New Zealand manager, says the information is consistent with the latest medical literature and safety data. “We have proactively ensured that data sheets and consumer medicine information are available on the MedSafe website, as well as the Sanofi website. All risks and benefits of this medication should be discussed between the patient and their doctor.”
Sanofi continues to closely monitor the safety profile of Epilim as more research is conducted, Carter adds.
At home in Howick with her daughters, Denise Astill is unimpressed by Sanofi’s response.
“There is no way I would have continued taking a drug that could cause birth defects, and it looks like some women continue to be unaware of the risks,” she retorts.
“We have children and adults out there who have this syndrome – we need to prevent it continuing to happen.”
BETTER WARNINGS NEEDED
Thalidomide was used in the 1950s and 60s to prevent morning sickness in pregnant women. Throughout the world about 10,000 cases were reported of babies born without arms or legs, or with just stumps. Other effects included deformed eyes and hearts, blindness and deafness. Many babies died and those who lived are now in their 50s.
Aucklander Helena Horswell, who calls herself a thalidomider, was born in 1962 with extremely shortened and malformed arms.
She is disappointed to hear of a medication causing birth defects in today’s world. She believes more explicit warnings would be helpful to prevent further birth defects.
“Warnings such as those on cigarette packs would be a start, but people soon get used to these. I would suggest that its use is only prescribed in females of child-bearing age after a counselling session.”
Horswell believes the responsibility lies with everyone involved in the chain before a pregnant woman swallows Epilim.
“I don’t know how much is being done to prevent misuse, and it will differ from country to country, but it sounds like a lot more could and should be done – not just by the prescribers and dispensers but by and at the cost of the manufacturer.”