Epilepsy drug behind up to 4,100 'severe birth defects' in France

April 20, 2017

The epilepsy medication valproate is responsible for "severe malformations" in 2,150 to 4,100 children in France since the drug was first marketed in the country in 1967, according to a preliminary study by French health authorities.

Women who took the drug during pregnancy to treat epilepsy were four times more likely to give birth to babies with congenital malformations, said the report, jointly issued by the French National Agency for the Safety of Medicines (ANSM) and the national health insurance administration.

"The study confirms the highly teratogenic"—that is, capable of causing birth defects —- "nature of valproate," said Mahmoud Zureik, scientific director of ANSM and a co-author of the report.

"The figure of about 3,000 severe malformations is very high," he told AFP.

The types of birth defects attributed to the drug included spina bifida—a condition in which the spinal cord does not form properly, and can protrude through the skin—as well as defects of the heart and genital organs.

The risk of autism and developmental problems was also found to be higher, and will be quantified in a follow-up report later this year.

An earlier estimate suggested that 30 to 40 percent of children exposed in the womb could suffer such disorders.

Risks known since 1980s

From 1967 to 2016, between 64,100 and 100,000 pregnancies in France were exposed to valproate, resulting in 41,200 to 75,300 live births, according to the report.

The vast majority of the birth defects occurred for women under treatment for epilepsy.

But starting in the late 1970s, valproate—marketed around the world as Depakine, Depakote, Stavzor and other trade names—was also prescribed in France to treat bi-polar disorder.

Bi-polar women taking the drug were twice as likely to give birth to children with major birth defects, the study found.

The lower risk compared with women treated for epilepsy probably stems from the fact that—for pregnant bi-polar women—doctors stopped prescribing valproate early in the pregnancy, Zureik said.

"The risk of severe malformation is limited to the first two trimesters of pregnancy," said Alain Weill, a researcher at the French health insurance administration and a co-author of the report.

The risk of birth defects associated with valproate has been known since the 1980s, especially for spina bifida, which occurs 20 times more frequently in foetuses exposed to the medication.

But the drug can still be prescribed to pregnant women when all other forms of treatment for epilepsy fail. That ruling, however, was put in place only in 2015.

Valproate is sold in France under the brand name Depakine by pharmaceutical giant Sanofi, but is also available in generic forms.

Inadequate warnings?

Some French families of children with birth defects born to women who took the drug while pregnant—grouped under an umbrella association called APESAC—have sued the company, claiming that it did not adequately warn about the risks.

"The number of victims is potentially huge," said APESAC president Marine Martin, who says two of her children—a girl and a boy—suffered physical defects brought on by valproate.

"We need to take into account children with malformations and autism, as well as families that lost a baby due to treatment during pregnancy," she told AFP.

Her association estimates a total of 30,000 to 50,000 victims—children and families included.

Gerard Bapt, a deputy in France's national assembly and a board member of ANSM, welcomed the report.

"It now appears fundamental that valproate in all its forms should not be prescribed for women of child-bearing age," he said in a statement. Medically necessary exceptions, he added, should be rare and accompanied by "mandatory contraceptive use".

In a statement, Sanofi said it had been "totally transparent with health authorities."

"We are aware of the painful situation confronting the families of children showing difficulties that may have a link with the anti-epileptic treatment of their mother during pregnancy," the drugmaker said.

France was last hit by a major drug scandal in 2010, when it was revealed that the off-label use of a diabetes drug called Mediator for weight-loss could cause fatal heart problems.

The legal fallout from that episode is still unfolding.

Explore further: 450 cases of birth defects from anti-epilepsy drug in France: health officials

Related Stories

450 cases of birth defects from anti-epilepsy drug in France: health officials

February 23, 2016
A common drug used to treat epilepsy has caused congenital defects in around 450 babies in France who were exposed to the medication before birth in the uterus, according to an estimate by health authorities published Tuesday.

France's Sanofi faces class action suit over epilepsy drug

December 13, 2016
An association of French women who took an epilepsy drug during pregnancy said Tuesday they would launch a class action against its maker, Sanofi.

Prescriptions for valproate not decreasing despite birth defect-causing concerns

July 24, 2013
A recent study shows that prescriptions for the antiepileptic drug valproate have not decreased in recent years even though the drug is known to cause severe birth defects and brain damage. A new study indicates that women ...

France moves to suspend Vitamin D supplement after baby dies

January 4, 2017
France has moved to suspend sales of a vitamin D medication following the death of a baby who suffocated after being given the liquid supplement, health authorities said Wednesday.

French govt denies hiding drug-related birth defects study

August 10, 2016
French health authorities are denying claims they concealed a study on a drug used to treat epilepsy that caused birth defects.

Task force offers recommendations on epilepsy treatments in women and girls

May 19, 2015
The anti-epilespy drug valproate should be avoided whenever possible in women who may become pregnant due to a high risk of malformations and developmental problems in babies who are exposed to the drug before birth.

Recommended for you

Mind-body therapies immediately reduce unmanageable pain in hospital patients

July 25, 2017
Mindfulness training and hypnotic suggestion significantly reduced acute pain experienced by hospital patients, according to a new study published in the Journal of General Internal Medicine.

Study suggests ending opioid epidemic will take years

July 20, 2017
The question of how to stem the nation's opioid epidemic now has a major detailed response. A new study chaired by University of Virginia School of Law Professor Richard Bonnie provides extensive recommendations for curbing ...

Team-based model reduces prescription opioid use among patients with chronic pain by 40 percent

July 17, 2017
A new, team-based, primary care model is decreasing prescription opioid use among patients with chronic pain by 40 percent, according to a new study out of Boston Medical Center's Grayken Center for Addiction Medicine, which ...

Private clinics' peddling of unproven stem cell treatments is unsafe and unethical

July 7, 2017
Stem cell science is an area of medical research that continues to offer great promise. But as this week's paper in Science Translational Medicine highlights, a growing number of clinics around the globe, including in Australia, ...

Popular heartburn drugs linked to higher death risk

July 4, 2017
Popular heartburn drugs called proton pump inhibitors (PPIs) have been linked to a variety of health problems, including serious kidney damage, bone fractures and dementia. Now, a new study from Washington University School ...

Most reproductive-age women using opioids also use another substance

June 30, 2017
The majority of reproductive-age and pregnant women who use opioids for non-medical purposes also use at least one other substance, ranging from nicotine or alcohol to cocaine, according to a University of Pittsburgh Graduate ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.