Article Text
PDF
Abstract
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.
Data availability statement
Data are available upon reasonable request.
Statistics from Altmetric.com
Data availability statement
Data are available upon reasonable request.
Footnotes
PP and EP are joint senior authors.
Contributors EH, PP and EP conceived and designed the systematic review. EH, GR, CBM, PP, FV, TOB and EP contributed to the conception and development of the study protocol. EH drafted the protocol and registered it on PROSPERO. EH, EP, and PP contributed to the data acquisition, analysis, and interpretation. EH is the first author and guarantor, PP is the corresponding author of the review. All authors reviewed, edited, and approved the final manuscript.
Funding EH is supported by an Australian Government Research Training Program (RTP) Scholarship. PP is supported by an Emerging Leadership Investigator Grant from the Australian National Health and Medical Research Council (APP2017651), the University of Melbourne, Monash University, the Austin Medical Research Foundation, and the Norman Beischer Medical Research Foundation.
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.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
Linked Articles
- Editorial commentary