UK Valproate Restrictions in Men Justified? New Data
A large Danish cohort study showed no significant increase in neurodevelopmental disorders (NDDs) among children fathered by men taking valproate during spermatogenesis, challenging earlier safety concerns and current UK restrictions on valproate use in men.
As previously reported by Medscape Medical News , the decision to restrict the drug in women and in men younger than 55 years was made in January 2024, after the UK Medicines and Healthcare products Regulatory Agency issued new guidance on the drug's use.
'Paternal exposure to antiseizure medication in association with conception is unlikely to pose any major risk for the offspring,' the investigators led by Jakob Christensen, DrMedSci, consultant neurologist at Aarhus University Hospital and professor at Aarhus University, Aarhus, Denmark, noted.
The study was published online on May 22 in JAMA Network Open .
Unnecessary Precaution?
In the US and Europe, there is strong guidance about avoiding valproate in pregnant women and women of childbearing age due to an elevated risk for birth defects and other developmental problems.
In January 2024, the European Medicines Agency's (EMA's) safety committee (Pharmacovigilance Risk Assessment Committee [PRAC]) expanded precautionary measures on valproate use to men considering fatherhood. The advisory was fueled largely by an observational study by the contract research organization IQVIA.
The study showed that about 5 out of 100 children had an NDD when born to fathers taking valproate during the 3 months before conception compared with about 3 out of 100 when born to fathers treated with lamotrigine or levetiracetam.
Last summer, Christensen and colleagues were unable to replicate the IQVIA results in a study using a subset of the same IQVIA data. However, at the time, only limited information about the IQVIA study was publicly available.
Once additional information from the IQVIA study became available, the researchers tried again to replicate the findings, aligning their methods more closely with the IQVIA study.
Despite using the same methodology and incorporating additional data, they were still unable to replicate the IQVIA findings. Their conclusion remained unchanged — there was no statistically significant increased risk for NDDs.
Specifically, among 961 children exposed to paternal valproate monotherapy and 1401 exposed to lamotrigine or levetiracetam, there was no significant increase in risk for NDDs (adjusted hazard ratio [aHR], 1.02; 95% CI, 0.67-1.54).
'This finding remained robust across analyses of specific NDDs, analyses of valproate dose, analyses accounting for time trends, analyses allowing for polytherapy, analyses expanding the definition of NDDs, analyses restricted to fathers with epilepsy, and analyses with a restricted exposure window,' Christensen and colleagues reported.
Restricting analyses to fathers with epilepsy of unknown cause yielded a higher risk (aHR, 2.48; 95% CI, 1.13-5.44), but this association was no longer significant in analyses matched on birth year (aHR, 2.33; 95% CI, 1.00-5.44).
Additional sensitivity analyses (restricting exposure window, excluding children with epilepsy or maternal epilepsy, and accounting for polytherapy) consistently showed no elevated risk for NDDs associated with paternal valproate exposure.
'We've examined this issue from many angles and still find no evidence supporting the concern behind EMA's recommendations,' Christensen said in a news release.
Will the EMA Reconsider?
Reached for comment, Aatif Husain, MD, epileptologist, neurologist, and sleep medicine specialist at DukeHealth, Durham, North Carolina, said, 'There seems to be a fair amount of literature' suggesting no increased risk for NDDs in children whose fathers use valproate.
'A recent systematic review that included 10 other studies came to this same conclusion,' said Husain, who wasn't involved in the Danish study.
Taken together, the data 'would probably move EMA to relook at their guidance to see if it needs to be modified,' he said.
Medscape Medical News reached out to the EMA press office for comment and received the following response.
'As with every medicine authorized in the EU, EMA continues monitoring and supervising the safety of these medicines. This includes monitoring information from various sources, such as spontaneous reports, clinical studies, scientific literature, and management of safety signals, which consists of a set of activities to determine whether there are new risks associated with an active substance or a medicine or whether known risks have changed. Should there be any updates, EMA will communicate them via the PRAC Highlights.'
Husain told Medscape Medical News that neither the FDA nor the American Epilepsy Society has issued guidance on valproate use in men 'because the data has not been strong enough.'
Hashtags
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
Yahoo
2 hours ago
- Yahoo
Toxic 'forever chemical' showing up in European food and wine
A team of researchers has found "alarmingly high" levels of trifluoroacetic acid (TFA), a so-called forever chemical, in dozens of organic and non-organic pastas, baked goods and breakfast cereals from Europe, as well as in wine. "In conventional grain products, the average levels were so high that a health risk to children can no longer be ruled out," said Helmut Burtscher-Schaden, an environmental chemist part of the Brussels-based Pesticide Action Network (PAN) Europe, which describes TFA as a "product of PFAS pesticides and industrial chemicals." Forever chemicals, also known as PFAS, are thousands of long-lasting substances used in household and everyday products since the middle of the 20th century but which have been found to be difficult to remove from the environment and from human bodies. The latest research points to 'widespread contamination from PFAS (per- and poly-fluoroalkyl substances) pesticides," PAN Europe said, warning that TFA tends to build up in water and farmland. The amount of TFA in the food items was found to be three times that recorded in a similar study eight years ago, according to PAN Europe, which in April warned of "dramatic rise" of TFA in wine. In a report covering wines from Austria, Belgium, Croatia, France, Germany, Greece, Hungary, Italy, Luxembourg and Spain, PAN Europe found that while pre-1988 vintages do not contain any such contamination, there has been a "sharp increase" in pesticide and chemical residues in wine bottled since 2010. Such a "steep accumulation" should be "a red flag that calls for decisive action," according to Michael Müller, a professor of pharmaceutical and medicinal chemistry at the University of Freiburg. The European Chemicals Agency has warned that TFA "may cause harm to the unborn child" and "may impair fertility."
Fox News
3 hours ago
- Fox News
First-known puberty blocker patient says 'insulting' youth gender movement makes mockery of true dysphoria
The first known patient to take puberty blockers to treat gender dysphoria sharply rebuked the modern youth gender identity movement as "insulting" in a podcast interview with the New York Times published last week. The Times spoke with "FG," a patient in adolescent transgender medicine from the Netherlands, who was the first known person given puberty blockers at 13years-old in the 1980s to stop female development. "FG" explained dealing with anger issues as a child and feeling uncomfortable living as a girl. The fear of going through puberty led the teen to express suicidal thoughts in a letter and eventually seek out medical treatment to stop normal development, as well as cross-sex hormones and gender reassignment surgery later on. Now, living as a man decades later with no regrets, "FG" believes puberty blockers "saved my life." Despite being a proponent of these medical interventions, "FG" was not supportive of the modern gender diversity movement. "So many of the young people now want to visibly challenge the binary," New York Times reporter Azeen Ghorayshi told "FG," asking, "What do you make of that? And what do you make of what that means for getting the medical treatment that you pioneered?" "I find that it's gone — it's gone a bit extreme to the other side," "FG" replied. "So it makes a laughingstock of what it's really about. Or at least, it seems to be a fashion statement nowadays." "FG" equated the current gender climate to other youth rebellion movements of the past where young people forged their identities "to stand out," saying gender seemed to be another forum for that today. "And for the group that is pure, like proper transsexuals, this flirting with pronouns and gender identity — it's insulting," "FG" continued. "FG", who works in the medical field and asked to stay anonymous out of a desperate desire to fit in as a man, said it seemed like young people now treat their gender identity as a fad. "Because like I said, we spend all our time trying to just fit in or be able to live the life that we feel we should have had. And it's not a great help when you've got people shouting from the barricades and trying to give you a different position, a third sex or whatever, and then talk about things that we don't want you to talk about, so that they can identify you," "FG" added. "I don't take a lot of these people that seriously, because it does seem to be a bit of a fashion statement." Shortly after taking office for his second term, President Donald Trump signed an executive order cutting off federal funding for institutions who engage in "chemical and surgical" sex-change procedures for minors. "Across the country today, medical professionals are maiming and sterilizing a growing number of impressionable children under the radical and false claim that adults can change a child's sex through a series of irreversible medical interventions," the order, titled "Protecting Children from Chemical and Surgical Mutilation," states. "This dangerous trend will be a stain on our Nation's history, and it must end." A number of hospitals nationwide challenged the order earlier this year, with some vowing to continue providing these medical interventions for minors.
Associated Press
3 hours ago
- Associated Press
Cryptobiotix Announces Its Next Evolutionary Step with Its Biobank Initiative to Accelerate Microbiome Innovation
06/10/2025, Ghent, Belgium // PRODIGY: Feature Story // Cryptobiotix, a next-generation preclinical research organization pioneering microbiome modeling through its proprietary SIFR platform, announces the launch of its biobank, marking the next phase in its continuous evolution. Co-founders Aurélien Baudot and Dr. Pieter Van den Abbeele founded Cryptobiotix to solve a critical gap in the field: the dreaded Valley of Death. Traditional preclinical testing is still slow or inaccurate, this could lead not only to delays but ultimately threaten the overall product development and launch. Now, with the launch of its biobank, the company is not just optimizing that core mission. It's redefining what's possible in microbiome research. 'We've always focused on delivering actionable insights, with the highest standards of scientific integrity, all while keeping to the tight deadlines our clients require,' says Baudot. 'We already had a streamlined process, but the biobank takes it to the next level. It's a small internal improvement, but one that has an exponential impact on our clients' workflows.' The Cryptobiotix biobank is more than just a freezer. It is a storage solution where cryo-stabilized gut microbiome samples are sourced, characterized, and stored under proprietary conditions that preserve both structure and function. This allows clients to build or tap into pre-qualified, pre-characterized microbiome samples instantly, bypassing weeks (sometimes months) of sourcing delays. In typical studies, donor sourcing can extend project timelines by two to eight weeks. But now, with tailored microbiome 'vaults' built to client specifications, those timelines shrink dramatically. Beyond speed, the biobank dramatically improves data granularity. Instead of working with random microbiomes, Cryptobiotix clients can now access specific metadata, such as diet, delivery method, age, country of origin, and more, to correlate clinical results to individual microbiome traits. 'It gives us immediate access to not just a 'baby microbiome,'' explains Dr. Van den Abbeele. 'It provides us access to a C-section baby, breastfed, and born in a specific country. This kind of clarity allows our partners to refine their experiment to the specific needs of their own business.' This opens the door for better responder/non-responder analysis and more refined product design, all essential for consumer health companies, nutrition innovators, and pharma organizations. The biobank fits seamlessly into Cryptobiotix's ex vivo modular SIFR platform, which simulates the entire gastrointestinal tract to understand the interplay between test products and the gut microbiome across individuals. By combining high throughput with validated predictivity, the company reduces development time and risk for clients worldwide. Cryptobiotix's research and development have also expanded into disease-rate simulation, including antibiotic-induced dysbiosis, acute infections, and Clostridium difficile modeling, helping therapeutic developers understand how interventions behave in both healthy and disrupted microbiomes. The company's precision is unmatched, wherein clients get a clearer view of how interventions truly behave in humans. While the launch of the biobank is an exciting milestone for the Cryptobiotix team, it is a natural, incremental evolution in its long-term strategy. 'For us, this is a stepping stone,' the founders say. 'We're already leveraging the data generated to train smarter analytics because the real future lies in making sense of complex microbiome datasets in ways the industry hasn't seen before.' Cryptobiotix is already exploring how its biobank can support longitudinal sample tracking, enabling comparisons of the same microbiome over time, even as donors' diets or health statuses change. This could offer clients unprecedented insights into microbiome stability, intervention reproducibility, and formulation refinements. With its cryo-stabilization method, perfected through hundreds of iterations, Cryptobiotix ensures the microbiome samples stored in its biobank retain their identity, empowering clients to revisit, reuse, and retest on demand. Media Contact Name: Cryptobiotix Team Email: [email protected] There is no offer to sell, no solicitation of an offer to buy, and no recommendation of any security or any other product or service in this article. Moreover, nothing contained in this should be construed as a recommendation to buy, sell, or hold any investment or security, or to engage in any investment strategy or transaction. It is your responsibility to determine whether any investment, investment strategy, security, or related transaction is appropriate for you based on your investment objectives, financial circumstances, and risk tolerance. Consult your business advisor, attorney, or tax advisor regarding your specific business, legal, or tax situation.
