The prevalence of neurodevelopmental disorders in children prenatally exposed to antiepileptic drugs
Rebecca Bromley,George E. Mawer,Maria Briggs,Christopher P Cheyne,Jill Clayton-Smith,Marta García-Fiñana,Rachel Kneen,S. B. Lucas,Rebekah Shallcross,Gus A. Baker +9 more
TLDR
An accumulation of evidence demonstrates that the risks associated with prenatal sodium VPA exposure include an increased prevalence of neurodevelopmental disorders, whether such disorders are discrete or represent the severe end of a continuum of altered neuro developmental functioning requires further investigation.Abstract:
The aim of this study was to compare the prevalence of diagnosed neurodevelopmental disorders in children exposed, in utero, to different antiepileptic drug treatments. A prospective cohort of women with epilepsy and a control group of women without epilepsy were recruited from antenatal clinics. The children of this cohort were followed longitudinally until 6 years of age (n=415). Diagnosis of a neurodevelopmental disorder was made independently of the research team. Multiple logistic regression analysis revealed an increase in risk of neurodevelopmental disorders in children exposed to monotherapy sodium valproate (VPA) (6/50, 12.0%; aOR 6.05, 95%CI 1.65 to 24.53, p=0.007) and in those exposed to polytherapy with sodium VPA (3/20, 15.0%; aOR 9.97, 95% CI 1.82 to 49.40, p=0.005) compared with control children (4/214; 1.87%). Autistic spectrum disorder was the most frequent diagnosis. No significant increase was found among children exposed to carbamazepine (1/50) or lamotrigine (2/30). An accumulation of evidence demonstrates that the risks associated with prenatal sodium VPA exposure include an increased prevalence of neurodevelopmental disorders. Whether such disorders are discrete or represent the severe end of a continuum of altered neurodevelopmental functioning requires further investigation. Replication and extension of this research is required to investigate the mechanism(s) underpinning the relationship. Finally, the increased likelihood of neurodevelopmental disorders should be communicated to women for whom sodium VPA is a treatment option.read more
Citations
More filters
Journal ArticleDOI
In Utero Exposure to Valproic Acid Induces Neocortical Dysgenesis via Dysregulation of Neural Progenitor Cell Proliferation/Differentiation.
TL;DR: It is shown that VPA decreases the probability of differentiation of the neural progenitor cells (NPCs) in mice, resulting in an abnormally increased number of projection neurons in the superficial layers of the neocortex.
Journal ArticleDOI
The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs.
TL;DR: The severity of the neurodevelopmental deficits associated with prenatal exposure to valproate highlight the critical need to consider neuro developmental outcomes as a central aspect of teratological research.
Journal ArticleDOI
Behavioral improvements in a valproic acid rat model of autism following vitamin D supplementation.
TL;DR: Early vitamin D supplementation in infant rat with ASD induced by VPA significantly improved development and behavior of rats related with ASD.
Journal ArticleDOI
Tactile stimulation improves neuroanatomical pathology but not behavior in rats prenatally exposed to valproic acid.
TL;DR: The results suggest that postnatal TS, during a critical period in development, acts as a powerful reorganization tool that can ameliorate the neuroanatomical consequences of prenatal VPA exposure.
Journal ArticleDOI
Using Zebrafish to Model Autism Spectrum Disorder: A Comparison of ASD Risk Genes Between Zebrafish and Their Mammalian Counterparts.
Victoria Rea,Terence J. Van Raay +1 more
TL;DR: What is known about those 12 ASD risk genes in human, mice and zebrafish and several non-genetic models including pharmacological and gnotobiotic models that are used in zebra fish to study ASD are described.
References
More filters
Journal ArticleDOI
The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial.
Anthony G Marson,Asya M Al-Kharusi,Muna Alwaidh,Richard Appleton,Gus A. Baker,David Chadwick,Celia Cramp,Oliver C Cockerell,PN Cooper,Julie Doughty,Barbara Eaton,Carrol Gamble,Peter Goulding,Stephen Howell,Adrian Hughes,Margaret Jackson,Ann Jacoby,Mark Kellett,G. R. Lawson,John Paul Leach,Paola Nicolaides,Richard C. Roberts,Phil Shackley,Jing Shen,David F. Smith,Philip E. M. Smith,Catrin Tudur Smith,Alessandr a Vanoli,Paula R Williamson +28 more
TL;DR: Valproate is better tolerated than topiramate and more efficacious than lamotrigine, and should remain the drug of first choice for many patients with generalised and unclassified epilepsies, and because of known potential adverse effects of valproate during pregnancy, the benefits for seizure control in women of childbearing years should be considered.
Journal ArticleDOI
Maternal lifestyle factors in pregnancy risk of attention deficit hyperactivity disorder and associated behaviors: Review of the current evidence
Karen Markussen Linnet,Søren Dalsgaard,Carsten Obel,Kirsten Wisborg,Tine Brink Henriksen,Alina Rodriguez,Arto J. Kotimaa,Irma Moilanen,Per Hove Thomsen,Jørn Olsen,Marjo-Riitta Järvelin +10 more
TL;DR: Exposure to tobacco smoke in utero is suspected to be associated with ADHD and ADHD symptoms in children and other maternal lifestyle factors during pregnancy may also beassociated with these disorders.
Journal ArticleDOI
Cognitive Function at 3 Years of Age after Fetal Exposure to Antiepileptic Drugs
Kimford J. Meador,Gus A. Baker,Nancy Browning,Jill Clayton-Smith,Deborah T. Combs-Cantrell,Morris J. Cohen,Laura A. Kalayjian,Andres M. Kanner,Joyce Liporace,Page B. Pennell,Michael Privitera,David W. Loring +11 more
TL;DR: In utero exposure to valproate, as compared with other commonly used antiepileptic drugs, is associated with an increased risk of impaired cognitive function at 3 years of age, and this finding supports a recommendation thatValproate not be used as a first-choice drug in women of childbearing potential.
Journal ArticleDOI
Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry.
Torbjörn Tomson,Dina Battino,Erminio Bonizzoni,John Craig,Dick Lindhout,Anne Sabers,Emilio Perucca,Frank J.E. Vajda +7 more
TL;DR: The risk of major congenital malformations is influenced not only by type of antiepileptic drug, but also by dose and other variables, which should be taken into account in the management of epilepsy in women of childbearing potential.
Journal ArticleDOI
Searching for ways out of the autism maze: genetic, epigenetic and environmental clues
TL;DR: Takeaway is that a unifying view of complex pathogenetic pathways that are likely to lead to autism spectrum disorders through altered neurite morphology, synaptogenesis and cell migration is provided.