Paternal exposure to antiseizure medications and offspring outcomes: a systematic review.

BACKGROUND

Concerns have recently been raised about risks to the fetus resulting from paternal exposure to antiseizure medications (ASMs). To address these concerns, we conducted a systematic review of the literature to assess neurodevelopmental and anatomical outcomes in offspring born to fathers taking ASMs at the time of conception.

METHODS

Electronic searches of MEDLINE, PsycINFO, and Embase were conducted to identify human studies published in English that reported on outcomes, comprising neurodevelopmental disorders, major congenital malformations, small-for-gestational age or low birth weight, in offspring of fathers taking ASMs at conception. Quality analysis of included studies was undertaken using the Newcastle-Ottawa Scale. A narrative synthesis was used to report study findings.

RESULTS

Of 923 studies identified by the search and screened by title and abstract, 26 underwent full-text review and 10 met eligibility criteria. There was limited evidence available, but there appeared to be no clear evidence for an adverse impact of paternal ASM use on offspring outcomes. Few isolated adverse findings were not replicated by other investigations. Several methodological limitations prevented meta-analysis, including failure by most studies to report outcomes separately for each individual ASM, heterogeneity in measurement and outcome reporting, and small numbers of monotherapy exposures.

CONCLUSIONS

Although there were limited data available, this systematic review provides reassuring evidence that paternal exposure to ASMs at conception is unlikely to pose any major risk of adverse outcomes for the offspring. Further research is needed to examine the relationship between preconception ASM use in males and offspring outcomes at birth and postnatally.

Informations de copyright

© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: CBM has received conference travel support and/or speaker fees from Merck, Novartis, and Biogen. He has received research support from the National Health and Medical Research Council, Multiple Sclerosis Research Australia, the University of Melbourne, the Royal Melbourne Hospital Neuroscience Foundation, and Dementia Australia. TOB has received research support from the Epilepsy Society of Australia, National Health and Medical Research Council, Royal Melbourne Hospital Neuroscience Foundation, Sanofi-Aventis, UCB Pharma, Janssen-Cilag, Novartis, and Sci-Gen. EP received speaker’s or consultancy fees from Eisai, GRIN Therapeutics, Shackelford Pharma, Sintetica, SKL Life Science, Sun Pharma, Takeda, UCB Pharma and Xenon Pharma and royalties from Wiley, Elsevier, and Wolters Kluwers. He is also on the board of EURAP-International Registry of Antiepileptic Drugs and Pregnancy, a non-profit organization which received financial support from Accord, Angelini, Bial, EcuPharma, Eisai, Glenmark, GW Pharma, GlaxoSmithKline, Sanofi, SF Group, Teva, UCB, and Zentiva. PP has received speaker honoraria or consultancy fees to his institution from Chiesi, Eisai, LivaNova, Novartis, Sun Pharma, Supernus, and UCB Pharma, outside of the submitted work. He is an Associate Editor for Epilepsia Open. He is also on the board of EURAP-International Registry of Antiepileptic Drugs and Pregnancy, a non-profit organization which received financial support from Accord, Angelini, Bial, EcuPharma, Eisai, Glenmark, GW Pharma, GlaxoSmithKline, Sanofi, SF Group, Teva, UCB, and Zentiva. GR has received speaker honoraria from Liva Nova. FV has received research support for the Australian Pregnancy Register from the Epilepsy Society of Australia, National Health and Medical Research Council, Royal Melbourne Hospital Neuroscience Foundation, Epilepsy Action Australia, Sanofi-Aventis, UCB Pharma, Janssen-Cilag, Novartis, and Sci-Gen. He is also on the board of EURAP-International Registry of Antiepileptic Drugs and Pregnancy, a non-profit organization which received financial support from Accord, Angelini, Bial, EcuPharma, Eisai, Glenmark, GW Pharma, GlaxoSmithKline, Sanofi, SF Group, Teva, UCB, and Zentiva. EH does not have any conflicts of interest to disclose.