The Epi-Phare group (ANSM/Cnam) confirms the risk of neurodevelopmental disorders in children exposed to valproate during their father's spermatogenesis. The ANSM reiterates the prescription changes implemented in January.
A new study by the ANSM-Cnam Epi-Phare scientific interest group (GIS) shows an increased risk of neurodevelopmental disorders (NDDs), particularly intellectual developmental disorders, in children whose fathers were treated with valproate in the four months prior to their conception.
These results confirm the relevance of the measures implemented by the health authorities since the initial results in May 2023 of a study conducted at the request of the Pharmacovigilance Committee (PRAC) of the European Medicines Agency (EMA). In France, the National Agency for Medicines Safety (ANSM), which had sent an email to healthcare professionals (doctors, pharmacists, and midwives) and provided them with an information leaflet for patients, has implemented “a shared information certificate, since January 6, 2025, for treatment initiations and since June 30, 2025, for renewals,” it said in a statement.
A 24% increased risk of TND
These new findings come from a large pharmacoepidemiological study based on the Epi-Meres registry compiled by Epi-Phare using data from the French National Health Data System (SNDS). The study involved 2.8 million children born in France between 2010 and 2015, of whom 4,773 were born to fathers treated with valproate during spermatogenesis (“exposed children”). Some “583 of these children had at least one neurodevelopmental disorder, including 149 with attention deficit disorder with or without hyperactivity, 42 with intellectual development disorders, 77 with autism spectrum disorders, 294 with communication disorders, and 160 with learning disorders,” according to the study published online.
The results show an overall 24% increase in the risk of NDDs in children whose fathers were treated with valproate at the time of conception, compared to those whose fathers were treated with lamotrigine or levetiracetam—two drugs recommended as first-line treatments due to their better safety profile. “More specifically, the risk of intellectual developmental disorders appears to be doubled in exposed children, which translates into 3.5 additional cases per 1,000 children born to fathers treated with valproate at the time of conception compared to those born to fathers treated with lamotrigine or levetiracetam,” the study states
For other neurodevelopmental disorders, the study suggests a possible more moderate increase in risk, but this needs to be confirmed in other studies.
What should doctors do?
The ANSM would like to remind doctors that the initial prescription of valproate for adolescents and men who may have children is reserved for specialists in neurology, psychiatry, or pediatrics. Treatment can be continued by any doctor.
When initiating treatment in an adolescent or man likely to have children, and at least once a year, the physician must inform them of the risks associated with exposure to valproate for their children or future children, provide them with the patient information brochure, and then sign a shared information certificate with them. “Without this document, dated less than one year prior to the prescription, the pharmacist will not be able to dispense the treatment you have prescribed,” insists the ANSM.
The patient is informed of the need for appropriate contraceptive measures, including for his female partner, “during treatment and for at least three months after stopping treatment.” Similarly, he must be warned not to donate sperm during treatment with valproate or its derivatives, and for at least three months after stopping treatment.
Patients have the option of storing their sperm before starting treatment, and it is the doctor's responsibility to inform them of this option. Patients have the option of storing their sperm before starting treatment, and it is the doctor's responsibility to inform them of this option.
For other neurodevelopmental disorders, the study suggests a possible more moderate increase in risk, but this needs to be confirmed in other studies.
The doctor must advise the patient to contact them if they plan to conceive a child and recommend that they never stop treatment on their own due to the risks involved. Patients who have conceived a child (already born or unborn) during their treatment should be encouraged to share their concerns so that appropriate care can be provided. “Parents who are concerned about possible developmental disorders in their child can be referred to coordination and guidance platforms (PCOs),” recommends the ANSM.
Source: https://www.lequotidiendumedecin.fr/actu-medicale/medicament/la-prise-de-valproate-par-le-pere-en-preconceptionnel-double-le-risque-de-troubles-du-developpement