Abstract
Objective: Prenatal exposure to antiepileptic drugs (AEDs) and in particular valproate (VPA) has been shown to impair intellectual and language development in children, but the impact on memory functioning has not been thoroughly investigated. This study aimed to evaluate memory skills in school-age children who were exposed to AEDs prenatally. Method: The sample comprised of 105 children aged 6 to 8 years. Information on AED exposure, maternal epilepsy, pregnancy, and medical history was prospectively obtained. Children completed a neuropsychological assessment including measures of verbal and nonverbal memory. Results: Children exposed to VPA performed lower than expected on list learning, story recall, and figure recall tasks. Those exposed to VPA in a polytherapy regime achieved poorer verbal memory scores compared with other drug exposure groups. VPA dose was negatively correlated with both verbal and nonverbal memory measures. Language ability predicted performance on all verbal memory measures and VPA dose was an additional predictor of retroactive interference on the list learning task. Performance on figure recall was predicted by exposure to VPA in polytherapy. Children exposed to carbamazepine (CBZ) also showed a higher rate of impairment on nonverbal memory measures. Conclusion: Both verbal and nonverbal memory skills are at risk in children exposed prenatally to VPA, particularly in those exposed to higher VPA doses. There may also be a selective vulnerability of the medial temporal lobe to VPA exposure. Our data highlight the possibility that nonverbal memory may also be affected in children exposed to CBZ. These findings have significant implications for the provision of cognitive and educational strategies to children exposed to AEDs in utero.
| Original language | English |
|---|---|
| Pages (from-to) | 784-796 |
| Number of pages | 13 |
| Journal | Neuropsychology |
| Volume | 32 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 1 Oct 2018 |
Funding
This research was supported by the Murdoch Children’s Research Institute, the Royal Children’s Hospital, Department of Paediatrics at The University of Melbourne, and the Victorian Government’s Operational Infrastructure Support Program. It was supported by grants from the Australian Research Council (LP0669648), Apex Foundation, and Pearson Plc. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, the writing of the report, or in the decision to submit the article for publication. Amanda G. Wood had full access to all the data in the study and had final responsibility for the decision to submit for publication. Sarah Barton and Caroline Nadebaum were supported by Australian Postgraduate Award scholarships, and Amanda G. Wood was supported by a NHMRC postdoctoral fellowship grant (251755) and Postdoctoral Research Funding from Australian Rotary Health. The study would not have been possible without the efforts of Janet Graham and Alison Hitchcock from the Australian Pregnancy Register for Women with Epilepsy and Allied Disorders, whose work in identifying and liaising with the participants has been invaluable. The Australian Pregnancy Register is grateful for financial support for its operations from the NHMRC, Epilepsy Society of Australia, Epilepsy Action, and the Royal Melbourne Neuroscience Foundation as well as pharmaceutical industry, including Sanofi-Synthelabo, UCB Pharma, Janssen Cilag, Novartis, Esai, SciGen, and Pfizer, and past support from Glaxo. We also thank all of the families who gave so generously of their time to participate in this research. The information in this article and the manuscript itself has never been published either electronically or in print.
Keywords
- antiepileptic drugs
- children
- memory
- prenatal exposure
- valproate