"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," responded the drug’s manufacturer, Sanofi, which said it had been "transparent with health authorities".
Very high risks of birth defects
Sodium valproate was first introduced in France in 1967 and soon became one of the most effective and widely prescribed drugs globally. While in the UK, thousands of pregnant women are believed to have taken valproate since its sale in 1973.
According to a joint report by the French National Agency for Medicines and Health Products Safety (ANSM) and the national health insurance body, sodium valproate was taken by up to 100,000 pregnant women between 1967 and 2016. During that period, about 2,150 to 4,100 children were born with at least one major congenital disorder.
"The study confirms the highly teratogenic (capable of causing birth defects) nature of valproate," said Mahmoud Zureik, ANSM's scientific director and co-author of the report.
"The figure of about 3,000 severe malformations is very high."
Besides, the preliminary study found that mothers treated with sodium valproate for epilepsy had up to four times likelihood of giving birth to a malformed child. On the other hand, women treated for bipolar disorder had a lower risk but was still twice as likely to give birth to children with major birth defects.
“The lower risk for bipolar women was probably because doctors tended to stop prescribing the drug earlier in the pregnancy,” said Zureik.
Lawsuit ensued and action taken
Despite the risks to foetuses known in the early 1980s, the French government and the manufacturer did not give warnings about the drug’s side effects in time, according to the parents of the children affected.
Women who took the drug while pregnant and gave birth to children with birth defects, under an umbrella association known as Association for the Support of Parents with Anti-convulsant Syndrome (APESAC), are suing the pharmaceutical company for not warning them adequately of the risks.
“As scientific knowledge has improved regarding the risks associated with use of sodium valproate, particularly during pregnancy, Sanofi has been fully transparent with health authorities and initiated the updating of product medical information for doctors and patients,” according to Sanofi.
Last year, Dominique Martin, director-general of the ANSM acknowledged on French television that “there was a delay in informing mothers and families.”
Meanwhile, France had issued warnings in 2014, whereas the National Health Service (NHS) issued an alert in the UK earlier this month to advise that valproate should only be given to girls and women of childbearing age under specialist supervision, and only when other medications do not work.
"It now appears fundamental that valproate in all its forms should not be prescribed for women of childbearing age," said French MP Gerard Bapt who welcomed the report.
“Medically necessary exceptions should be rare and accompanied by mandatory contraceptive use,” he added. MIMS
What the pharmaceutical industry needs: Transparency and rigorous monitoring
Hundreds of women to take legal action on NHS over vaginal mesh implants
Online tool reveals up to 100% of research trials are never disclosed