UK class action lawsuit over Sodium Valproate birth defects

[drarvindr]

Generalized tonic clonic seizures during pregnancy can lead to increased maternal trauma. If the maternal trauma involves the abdomen, a theoretical risk of abruption exists, possibly leading to fetal hypoxia or death. Furthermore, the risk of maternal aspiration can lead to maternal hypoxia, which can also lead to fetal hypoxia. Evidence indicates seizure frequency increases during 17-33% of pregnancies.

At least , this is the prevailing medical opinion as of now.Tonic clonics are the major concern since the other forms are not as dangerous to the fetus , but any seizure disorder can move toward tonic clonics if you are off anti-epileptic drugs long enough. I went into status epilepticus (tonic clonic) when i behaved like a moron and stopped my meds for 3 months even though i normally get only myoclonic seizures. Seizure frequency sky rockets in pregnancy bcoz estrogen is epileptogenic in pregnancy ( it lowers the efficacy of anti-epileptic drugs by metabolising them faster).The body deals with emergencies by looking out for number one. Since , in a pregnant woman , there are two people and the body prioritises toward the mother.If she had gone into full blooded status epilepticus it could have been life threatening for your child. It is a complex risk benefit ratio thing. In your case , you were well trained over several years to deal with seizures. If she had aspirated or choked during a seizure , there was a chance of injury to your son. The current regimens advocate that anti-epileptic drugs be continued in pregnancy , but obviously changed so as not to harm the developing fetus. (different anti-epileptic drugs are bad at different trimesters)

Overall , doctors feel that given a choice between anti-epileptic drugs and status epilepticus , they choose anti-epileptic drugs. It is not an easy choice but better given the options. Of course , everyone is different and responds differently to anti-epileptic drug therapy , and there are chances of problems in pregnancies even with anti-epileptic drugs , and sometimes because of them.The risks of seizures in pregnancy are not "overblown" in my opinion , because not taking measures to remove a preventable risk of anything more than 1% would be unacceptable to me if it was my baby.

[Bernard]

... The risks of seizures in pregnancy are not "overblown" in my opinion , because not taking measures to remove a preventable risk of anything more than 1% would be unacceptable to me if it was my baby.

I was curious if anyone had been able to establish that the risk of problems to the child (from tonic clonic seizure activity) was more than 1%. With many anti-epileptic drugs, the increased risks for birth defects is more than 1% IIRC (anywhere from 2.7% to 7.3% if I'm reading this right).

...

I did some searching and found this study which describes a single case study showing a change in fetal heart rate during a complex partial seizure. The study has some footnotes, one of which is Management issues for women with epilepsy : A review of the literature (emphasis mine):

...
Avoidance of seizures during pregnancy is desirable for psychosocial and socioeconomic reasons as well as for the physical well-being of WWE. Potential mechanisms for fetal injury after an isolated generalized seizure include physical damage due to maternal abdominal trauma as well as hypoxic-ischemic injury due to decreased placental perfusion or maternal hypoxia. Sustained changes in fetal heart rate have been documented during maternal generalized seizures. There are rare case reports of intrauterine death after single seizures. The effects of partial complex seizures and absence seizures on the fetus are unknown and the potential long-term effects of an isolated tonic-clonic seizure on the cognitive development of the fetus have not been studied.
...
Two studies have reported outcomes for infants born in the last 10 years. Infants of WWE remain at risk despite changing management patterns. Jick and Terris reported a 3.4% malformation rate for infants of treated WWE with a control rate of 1%. Waters et al. reported a 10.7% rate of adverse outcomes compared with 3.4% in controls, but included neonatal death and major and minor malformations. The pattern of birth defects in the offspring of WWE may be changing with newer management strategies. King et al. compared a 1967 to 1980 cohort with a 1981 to 1992 cohort. Results indicated increased risk for orofacial clefts in the earlier group with a trend toward neural tube defects in the latter. This information may reflect increasing use of valproic acid and carbamazepine, which have been implicated in the development of neural tube defects in infants of WWE.

Studies also have examined seizure occurrence during pregnancy. Seizures during pregnancy are not linked to increased risk for malformations in infants of WWE in several major studies. An exception is Lindhout et al.'s report of a 12.3% malformation rate in WWE experiencing first trimester seizures compared with 4% in women without first trimester seizures.

It doesn't appear to me that there is a strong scientific basis for evaluating the risks.

[drarvindr]

Find a study that says women with status epilepticus in pregnancy had a better outcome without drugs , and i'll concede the point. Untill then , i still feel anti-epileptic drugs are better. "Adverse outcome" does not just mean for the fetus (malformations) , but for the mother as well , including complications faced during labor , cesareans , etc.
From your study :

Obstetric complications that have been reported to occur with increased frequency in WWE in various surveys include vaginal bleeding, hyperemesis gravidarium, ectopic pregnancy, spontaneous abortion, premature labor and preterm delivery, forceps or vacuum assisted delivery, cesarean section, stillbirth, and neonatal death. The adverse obstetric outcomes reported most consistently as increased for WWE are stillbirth and neonatal death.42,43 One study suggests that there has been a decline in perinatal deaths with current seizure management patterns. The rate for WWE in a 1977 to 1981 cohort was 4.7% (control, 1.5%) with the rate decreasing in the 1987 to 1991 cohort to 2.1% (control, 0.9%).44

Also,

long-term effects of an isolated tonic-clonic seizure on the cognitive development of the fetus have not been studied.

I wasn't talking about ISOLATED tonic clonics , i was referring to the increased risk from multiple tonic clonics as well as from status epilepticus (which is the larger worry).

In one study, medication noncompliance occurred in 68% of those WWE with worsened seizure control.45

Seizures during pregnancy are not linked to increased risk for malformations in infants of WWE in several major studies.

- i never said they were. I still say that they are a risk for IUGR(intra uterine growth retardation) and fetal loss (stillbirths and the like)

Nulman et al. reported a twofold increase in anomalies in children of WWE treated with phenytoin and carbamazepine, but also in the children of untreated WWE.64

If they are going to get malformations anyway , why have less seizure control and increase the obstetric risk and other risks from IUGR?

Malformations will always be more common with drugs , i agree with what you've said. Dead babies/ small and weak babies are more common if they don't get oxygen , which could likely happen in a state of status. Everyone knows that valproate and CMZ cause neural tube defects and should not be used in the first trimester.The neural tube is formed in the first month of pregnancy , when many women don't even know they are pregnant and keep taking these drugs unknowingly, which increases the likelihood of malformations due to these drugs and it is therefore not really proving anything, in my opinion to judge the outcome of changing managements in pregnancy unless everyone in the sample is a pre-planned pregnancy and they have been taking superdoses of folic acid before conception (shoddy science strikes again!). Ideally WWE should be told all of this by their neuros (which was my point to begin with - sue the doctors who neglected to mention all of this) and take these precautions when they are trying to conceive.I realise that this may sound offensive or patronising , but this is the only recourse since ALL anti-epileptic drugs cause some malformation or other at some point in the pregnancy. Once the neural tube is formed (or deformed , as the case may be) , there is nothing you can do to reverse the process in utero, which is why valproate can be given after the first trimester.My point is , given that people who suddenly stop their meds tend to go into status epilepticus ( i am (fortunately)living proof) , it is still a better deal to take meds (albeit with a reduced dosage) during pregnancy. Given that there is a 10-15% risk of mortality (and this is assuming you are young (figures are higher with increasing age)and not pregnant (the risk of getting seizures increases with pregnancy) for the mother and by extension ,a bit more for the fetus from status epilepticus , and also considering that the treatment of status involves pumping you full of anti-epileptic drugs which could harm the baby, isn't it better to have a smaller dosage of your drugs and avoid dire consequences ?

P.S. Bernard you really need to look into new spell check software. everything that i write in British spellings is underlined in red. i don't usually uze American spellingz ( )

[Bernard]

Thanks doc. It's an issue that I had not explored previously. I appreciate your comments. Food for thought for sure.

P.S. Bernard you really need to look into new spell check software. everything that i write in British spellings is underlined in red. i don't usually uze American spellingz ( )

There's a spell check?

You might be the only one using it.

[Aodan]

Everyone knows that valproate and CMZ cause neural tube defects and should not be used in the first trimester.The neural tube is formed in the first month of pregnancy , . sue the doctors who neglected to mention all of this[/B]) and take these precautions when they are trying to conceive.

drarvindr

Spoken like a true neurologist!!

One who has too much malpractice insurance, too many patients, too much money, and no warm human emotions!!!

"Everyone" does NOT know Valproate causes neural tube defects. Unfortunately there are far too many uninformed women going to their neurologists, and general practitioner for meds. These woman hang off every word that comes out of those doctors mouthes. "He's my doctor-why wouldn't he tell me something I needed to know". I've heard it far too many times-its sickening. If they are anywhere in the child-bearing age, their dr should step up and give them this information, not assume they know. You are reiterating pharma. inserts. "if the benefit outweighs the risk".

FYI: Depakote can also cause defects at the end of the second term, during the increased, organ, brain, and body growth.

Due to the way the UK system is set up, there is no recourse against the dr.'s. This info is from speaking with Body.

After 11 years of living, and researching, Depakote and its' in utero effects and working on such studies, it can do a lot of damage. Fetal Valproate Syndrome is a difficult and challenging condition for a child to live with.

[Aodan]

SKILLEFER

Let's face it....as my neurologist said, "There's no such thing as a safe anti-epileptic drug. They all have risks."

Is this very nonchalant attitude, toward the D/A article?

Sounds as though your neurologist has given up interest in his profession, which is sad.

Living with seizures myself, and a child with Fetal Valproate Syndrome (affected with Autism and a plethora of other conditions), it appears this kind of thinking from some in the general public, dr's, the FDA and pharmaceutical companies, is what has led to the problems resulting from Depakote.

ABBOTT spent the minimum amount on studies for FDA approval not for safety and toxicology. Their recourse for any human malformations is simple, "studies were not conducted on humans". And that my friend, sad though it makes me, comes straight from someone I spoke with at the FDA.

What is this world coming to?

[epileric]

SKILLEFER


Is this very nonchalant attitude, toward the D/A article?

Sounds as though your neurologist has given up interest in his profession, which is sad.

I actually see it as very responsible. I was often told that I can't live without meds & that I had no choice but to live with side-effects. I see acknowledging the fact that they all have side-effects to be more honest & gives the client the choice.

[drarvindr]

OK , Aodan ,
i havent replied thus far because i really don't get what you're accusing me of.
1) Let me reiterate (that means i say again, implying that this is what i meant) : I believe that it is the neurologists ' job to tell their patients that taking valproate may cause malformations.
2) by everyone , i implied everyone with a degree in medicine. not EVERYONE everyone. pardon the grammar .
3) You seem to have taken me out of context and the "quote " makes no sense.
4) I hope i spoke like a true neurologist. you flatter me .
5) sorry if i seem to be sniping but i've had a rough week changing upto 20 dressings a day and handling preops. its been hell :eyeroll:.

[Bernard]

In line with our discussion here:

New research suggests that it is largely the drugs used to treat epilepsy and not the condition itself that increase the risk of adverse pregnancy and birth outcomes.

"Epilepsy is the most common maternal neurologic disorder requiring medical treatment during pregnancy," Dr. Gyri Veiby, of Haukeland University Hospital, Bergen, Norway, and colleagues write. "Risks associated with medical treatment during pregnancy must be weighed against the risk for fetal or maternal complications due to epileptic seizures."

Using data from the population-based Medical Birth Registry of Norway, the researchers examined pregnancy and birth outcome in an unselected population of women with both treated and untreated epilepsy. The study included all births recorded from December 1, 1998, through 2005. The team compared 2861 deliveries by women with epilepsy to 369,267 non-epilepsy deliveries.

Of the 2861 epileptic women, 1900 (66%) did not use antiepileptic drugs during pregnancy. Overall, 961 pregnancies in the epilepsy group were exposed to antiepileptic drugs, mostly as monotherapy. Antiepileptic drugs used included carbamazepine, lamotrigine, valproate, oxcarbazepine, clonazepam, topiramate, phenytoin, phenobarbital, levetiracetam, gabapentin, and vigabatrin.

Infants who were exposed to antiepileptic drugs were more often preterm (p = 0.01), and more often had birth weight <2500 g (p < 0.001), head circumference <2.5 percentile (p < 0.001), and low Apgar score (p = 0.03) compared to non-epilepsy controls, according to the report in the September issue of Epilepsia.

Epilepsy group children were more often transferred to a pediatric ward during the neonatal period. This was especially true in antiepileptic drug-exposed infants. Small-for-gestational-age infants occurred more frequently in infants who were exposed to antiepileptic drugs (p = 0.05) and unexposed infants (p = 0.02) than in controls.

There was no significant difference in the frequency of major congenital malformations between the epilepsy group and the control group (2.8% versus 2.5%, respectively). Significantly higher rates of major congenital malformations and any congenital malformations were found in infants exposed to either valproate or polytherapy.

"Cardiovascular malformations were significantly more common in antiepileptic drug-exposed infants versus controls, and especially for valproate exposure," Dr. Veiby and colleagues explain. "In the untreated epilepsy group there was a higher occurrence of genital malformations."

Neonatal spina bifida was not significantly increased in the epilepsy group compared to the control group. Down syndrome was significantly more common in untreated epilepsy pregnancies compared to controls. Both spina bifida and Down syndrome were major indications for elective pregnancy termination among epileptic women. A higher rate of cesarean section was observed in the epilepsy group, regardless of antiepileptic drug-exposure (p < 0.001).

"Adverse pregnancy and birth outcome in women with epilepsy is mainly confined to antiepileptic drug-exposed pregnancies," the authors conclude, "although some risks are associated also with untreated epilepsy."

Epilepsia 2009;50:2130-2139.

http://www.reuters.com/article/healt...58L2MJ20090922

[Loudmouth]

As most of you know, I lost a baby at the end of last year. I AM on medication (gabapentin), but it has never fully controlled my seizures. I do not have tonic clonic seizures, I have atonic seizures and complex partial seizures. When I was 19 weeks pregnant, I had the longest complex partial seizure I have had before or since, and afterwards I didn't feel the baby move. It IS possible (in rare cases as I keep getting told) to lose a baby through a non-convulsive seizure. There were no congenital malformations in my son, it was deemed that it was lack of oxygen to him that did it. I had done everything I was meant to, being on an anti-epileptic drug with less risks, taking huge doses of folic acid before I conceived, but it still didn't work for me. When I have my seizures under better control, We will be trying for another baby, but until then, the risks are just too great, I couldn't go through that again. Just wanted to make the point that it is not only people who have tonic clonic seizures that this issue can affect. And I wasn't told about the folic acid by the GP or neurologist, it was through my own research and conversations with the volunteer from my local Epilepsy Action group. I am now permanently on high dose folic acid just in case my contraception fails (it has before!)

[Bernard]

Thanks for the sobering lesson Loudmouth. Condolences (again?).

Here in the USA, the FDA issued a reminder warning about Depakote (sodium valproate):

The FDA is reminding health care professionals about the increased risk of neural tube defects and other major birth defects, such as craniofacial defects and cardiovascular malformations, in babies exposed to valproate sodiumand related products (valproic acid and divalproex sodium) during pregnancy. The FDA will be working with the manufacturers of these products to address labeling changes.

Healthcare practitioners should inform women of childbearing potential about these risks, and consider alternative therapies, especially if using valproate to treat migraines or other conditions not usually considered life-threatening.

Women of childbearing potential should only use valproate if it is essential to manage their medical condition. Those who are not actively planning a pregnancy should use effective contraception, as birth defect risks are particularly high during the first trimester, before many women know they are pregnant.

FDA has required a patient Medication Guide for each antiepileptic drug (anti-epileptic drug), including valproate. The valproate Medication Guide will explain the benefits and risks of valproate and encourage patients to discuss options with their healthcare professional.

Valproate sodium is marketed as Depacon. Dilvalproex sodium is marketed as Depakote, Depakote complex partial, Depakote ER. Valproic acid is marketed as Depakene and as Stavzor.

Pregnant women using valproate or other anti-epileptic drugs should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334; www.aedpregnancyregistry.org).

This information reflects FDA's current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available.

To report any unexpected adverse or serious events associated with the use of this drug, please contact the FDA MedWatch program using the information at the bottom of the page.


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Background

FDA first approved Depakene (valproic acid) in 1978 for the treatment of epilepsy. More recently, FDA approved valproate for the treatment of bipolar disorder and migraine headaches. As valproate's indications for use expand, it is critical that all health care professionals caring for women of childbearing potential and taking valproate for any indication be informed that valproate causes an increased risk of major birth defects. Awareness of the therapeutic benefits and risks of valproate and alternative therapies, as well as the risks of untreated disease, is critical for informed prescribing and counseling of all women taking valproate.

Valproate and Birth Defect Risk

Valproate use during pregnancy increases the risk of major malformations, including neural tube defects. In the United States, about 1 in 1500 babies is born with a neural tube defect. The risk of neural tube defects is much higher in babies born to mothers treated with valproate during the first 12 weeks of pregnancy, with the risk increasing to 1 in 20 babies.

Data from the NAAED Pregnancy Registry show that the rate of major malformations in babies born to women with epilepsy taking valproate (monotherapy) is almost 4 times higher than the rate of major malformations in babies born to women with epilepsy taking a different antiepileptic drug. The NAAED Registry reported a major malformation rate of 10.7% (95% C.I. 6.3% – 16.9%) in the offspring of women exposed to an average of 1,000 mg/day of valproic acid monotherapy during pregnancy (dose range 500 – 2000 mg/day). The major malformation rate among the internal comparison group of 1,048 women with epilepsy who received any other antiepileptic drug monotherapy during pregnancy was 2.9% (95% CI 2.0% to 4.1%). Sixteen major malformations occurred in the offspring of 149 women who used valproate during pregnancy, and these malformations included neural tube defects, craniofacial defects, cardiovascular malformations and malformations involving other body systems.

Folic Acid and Neural Tube Defects

Studies in the general population show that folic acid supplementation prior to conception and during early pregnancy reduces the risk of neural tube defects. To ensure adequate folic acid intake, women of childbearing potential should use FDA approved folic acid prescription drugs and not rely on dietary intake or supplements alone.

Considerations for Health Care Professionals

• Valproate use during early pregnancy increases the risk of major malformations in the baby. The rates for neural tube defects in babies exposed to valproate during the first trimester are 30 to 80 times higher than the rate for neural tube defects in the general U.S. population. In pregnant women with epilepsy, valproate monotherapy is associated with a four-fold higher rate of major malformations than other antiepileptic drug monotherapies.
• Women of childbearing potential who are considering valproate therapy or who are taking valproate should be advised of both the risks of their medical condition and the medicines used to manage their condition.
• Healthcare professionals should counsel women of childbearing potential taking valproate about the increased risk of major malformations, including neural tube defects, when valproate is used during pregnancy.Healthcare practitioners should recommend use of effective contraception for women who are not planning a pregnancy and discuss the relative risk and benefits of appropriate alternative therapies.
• Untreated or inadequately treated epilepsy or bipolar disorder during pregnancy increases the risk of complications in both the pregnant mother and her developing baby.
• Healthcare professionals should inform patients that taking folic acid before and during the first trimester of pregnancy can decrease the risk for congenital neural tube defects.
• Available prenatal diagnostic testing to detect neural tube defects and other malformations should be offered to all women who become pregnant while taking valproate.
• Women who become pregnant while taking valproate or other antiepileptic drug (anti-epileptic drugs) are encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll-free number 1-888-233-2334. Information on the registry can also be found at the website www.aedpregnancyregistry.org. This registry gathers information about the effects of antiepileptic drugs during pregnancy.

Information for Patients:

• Using valproate during pregnancy increases the chance of having a baby with a birth defect. Neural tube defects, such as spina bifida, are the birth defects most often seen with valproate use in early pregnancy.These defects of the brain and spinal cord occur when the developing spinal canal does not close normally.
• For this reason, a woman of childbearing potential should generally not take valproate unless it is considered essential for her treatment. Women of childbearing potential are women who have passed puberty and have not passed through menopause and have not had their uterus or ovaries removed.
• Women of childbearing potential who do take valproate should use effective birth control (contraception) while taking valproate.
• Women who are planning a pregnancy or who become pregnant while taking valproate should contact their healthcare professionals immediately.They should talk to their healthcare professionals about the best way to treat their health conditions before and during pregnancy. Healthcare professionals may discuss other treatment options.
• Valproate should not be stopped without talking to a healthcare professional, even in pregnant women. Stopping valproate suddenly can cause serious problems. Not treating epilepsy or bipolar disorder can be harmful to women and their developing babies.
• Women who become pregnant while taking valproate or other antiepileptic drugs (anti-epileptic drugs) should consider enrolling in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. Women can do this by calling the toll-free number 1-888-233-2334. This pregnancy registry gathers information about the safety of antiepileptic drugs during pregnancy.
• It is important to know that birth defects also occur in babies born to women who are not taking any medicines and who do not have other risk factors, but they occur less often (in about 3 out of every 100 babies).
• Taking folic acid supplements before getting pregnant and during early pregnancy has been shown to lower the chance of having a baby with a neural tube defect.
• Women should tell their healthcare professionals about all the medicines they take, including prescription and non-prescription medicines, vitamins, and herbal supplements, and should not start a new medicine without first talking with a healthcare professional.

http://www.fda.gov/Drugs/DrugSafety/.../ucm192649.htm

[Ruth]

I saw from a commercial on TV from a law firm that their is a class action lawsuit over it in the US. I was pregnant with my last child in 1979. I was on Depakote. After I proudly told my neurologist that I was expecting, he told me to get an abortion. He told me that I was not to get pregnant on Depakote.

He knew I was still of child bearing years and he did not tell me about it when I was first on it. I told him that I was not going to kill my baby. Abortion is murder.

He has a birth defect from that time, that I cannot get the records. I have no idea where the neurologist is, that was 30 years ago. I do not know if I have a lawsuit. I am going to go ask that lawsuit class action lawer anyway.

My proof, Bernard, is that my neurologist told me that it could cause birth defects and that they were serious enough that he recommened that I have an abortion.

[JRuner]

I will be sure to warn any ladies that I and my wife know about this drug. My birth defects are from a drug related to thalidomide but all I know is it starts with the letter "G". They really need to be cautious giving a pregnant woman any drugs period!

John

[Ruth]

I have had two bouts of status epilepticus in my life. Having seizures during pregnancy, could kill a baby. A lot of us have had some hard falls during our tonic clonics.

I would rather be on medications and take my chances. Either way, we are taking chances when we have babies/w/epilepsy.

What about birth defects if it is the father who has epilepsy? The medicine he is on can cause birth defects, too.

Thank you drarvindr for this important information that we all can use. I appreciate your knowledge. we need it here. How long before you become a neurologist?

[Bernard]

I saw from a commercial on TV from a law firm that their is a class action lawsuit over it in the US.

Interesting. Do you remember any details from the commercial (ie. law firm, phone number, etc.)?

I can't find anything on the internet about a class action suit here in the USA, mostly law firms wanting to represent individual cases.

[Bernard]

CWE's newest sponsor is recruiting candidates for depakote lawsuits over birth defects here in the USA. They are pushing for a class action lawsuit.