Paternal antiseizure meds have little impact on offspring

Men who take antiseizure medications for epilepsy have higher rates of psychiatric comorbidities and erectile dysfunction, but do not face a higher risk of adverse birth outcomes or conceiving a child with neurodevelopmental disorders, according to a study out of the Icahn School of Medicine at Mount Sinai, New York.

“Notably, about 18% of children born to fathers on antiseizure medications experienced neurodevelopmental delays, compared with 2% of controls. However, although there was a trend, this was not statistically significant,” reported Nicolas Lemus, MD, first author of the study, at the virtual meeting of the American Academy of Neurology.

“There was no statistically significant differences in the rates of [low birth] weight, time for conception, or prematurity,” he added.

The single-center, retrospective, questionnaire-based analysis included men recruited from a general neurology clinic – 110 of whom did not have epilepsy and 110 of whom were taking antiseizure medications for epilepsy.

Men who had children were asked about the health of their offspring, while all participants were asked about erectile dysfunction and psychiatric comorbidities.

A total of 7 out of 38 (18.42%) children whose fathers were on antiseizure medications at the time of conception had developmental delays, compared with 1 (2.63%) out of the same number of children from age-matched fathers who did not have epilepsy (P = .056).

In addition, among men taking antiseizure medications there was “a higher rate of psychiatric comorbidities such as major depressive disorder, bipolar disorder, and suicidal ideation when compared to the control group,” reported Dr. Lemus (42.27% vs. 20.91%, P < .001).

And a higher rate of men on antiseizure medications reported erectile dysfunction, compared with men without epilepsy (17.27% vs. 6.36%, P = .0202).

“There is extensive data regarding side effects of antiseizure medication in women – particularly teratogenicity and offspring neurodevelopmental disorders,” but comparatively “few studies which evaluate the effect of antiseizure medications on men’s sexual function, and the offspring of men who use antiseizure medications during conception,” noted Dr. Lemus.

Levetiracetam was the antiseizure medications used by most study participants (47.27%), followed by lamotrigine (21.82%).

Other evidence

In contrast to the small Mount Sinai study, a large Swedish registry study suggests no link between paternal antiepileptic medication and adverse outcomes in offspring.

That study included 1,144,795 births to 741,726 fathers without epilepsy and 4,544 births to 2,955 fathers with epilepsy.

Just under half of the babies born to fathers with epilepsy (n = 2,087) had been conceived while their fathers were taking antiepileptic drugs. Compared with babies whose fathers had epilepsy but were not taking antiepileptic drugs they had no greater  risk of major congenital malformations (adjusted odds ratio, 0.9; 95% confidence interval, 0.7-1.2), autism (adjusted hazard ratio; 0.9; 95% CI, 0.5-1.7), ADHD (aHR, 1.1; 95% CI, 0.7-1.9), or intellectual disability (aHR, 1.3; 95% CI, 0.6-2.8).

Although valproate monotherapy was linked to slightly higher rates of autism and intellectual disability, this did not reach statistical significance in the propensity score–adjusted analyses.