Rebecca L Bromley1, Gus A Baker2. 1. Division of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK; Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. Electronic address: Rebecca.bromley@manchester.ac.uk. 2. Department of Molecular and Clinical Pharmacology, University of Liverpool, UK.
Abstract
PURPOSE: Data highlighting valproate as a human teratogen put in context the need to balance both maternal and fetal needs; maximising maternal health whilst minimising fetal risk. This led to increased research efforts to understand the associated risks with AED treatments. METHODS: A review of currently published literature was undertaken. RESULTS: In utero exposure to valproate was associated with a range of poorer neurodevelopmental outcomes when compared to control children and children exposed to other antiepileptic drugs (AEDs). Children exposed to carbamazepine were not found by the majority of studies to have poorer early development, although there is a lack of evidence regarding specific cognitive skills later in childhood and adolescence. Research regarding lamotrigine was limited to a small number of studies but suggests early global development or school aged IQ does not differ from control children, but less is known about specific cognitive skills. Evidence for the other AEDs including levetiracetam and topiramate were significantly limited. CONCLUSIONS: Despite an improvement in momentum the evidence remains incomplete for neurodevelopmental outcomes and this limits evidence-based decision making. Further efforts are required to enhance the treatment of women by giving them the confidence that both the risks and the benefits of commonly used AEDs are known. Future research should also seek to increase our understanding of the children who experience neurodevelopmental difficulties in the context of exposure in the womb to AEDs and what interventions may be successful in maximising the outcome of these children.
PURPOSE: Data highlighting valproate as a human teratogen put in context the need to balance both maternal and fetal needs; maximising maternal health whilst minimising fetal risk. This led to increased research efforts to understand the associated risks with AED treatments. METHODS: A review of currently published literature was undertaken. RESULTS: In utero exposure to valproate was associated with a range of poorer neurodevelopmental outcomes when compared to control children and children exposed to other antiepileptic drugs (AEDs). Children exposed to carbamazepine were not found by the majority of studies to have poorer early development, although there is a lack of evidence regarding specific cognitive skills later in childhood and adolescence. Research regarding lamotrigine was limited to a small number of studies but suggests early global development or school aged IQ does not differ from control children, but less is known about specific cognitive skills. Evidence for the other AEDs including levetiracetam and topiramate were significantly limited. CONCLUSIONS: Despite an improvement in momentum the evidence remains incomplete for neurodevelopmental outcomes and this limits evidence-based decision making. Further efforts are required to enhance the treatment of women by giving them the confidence that both the risks and the benefits of commonly used AEDs are known. Future research should also seek to increase our understanding of the children who experience neurodevelopmental difficulties in the context of exposure in the womb to AEDs and what interventions may be successful in maximising the outcome of these children.
Authors: Elisabeth Synnøve Nilsen Husebye; Nils Erik Gilhus; Bettina Riedel; Olav Spigset; Anne Kjersti Daltveit; Marte Helene Bjørk Journal: Neurology Date: 2018-08-01 Impact factor: 9.910
Authors: Andrea V Margulis; Sonia Hernandez-Diaz; Thomas McElrath; Kenneth J Rothman; Estel Plana; Catarina Almqvist; Brian M D'Onofrio; Anna Sara Oberg Journal: PLoS One Date: 2019-08-05 Impact factor: 3.240