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
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Neurodevelopmental Effects of Fetal Antiepileptic Drug Exposure
TL;DR: Overall, children exposed to polytherapy prenatally appear to have worse cognitive and behavioral outcomes compared withChildren exposed to monotherapy, and with the unexposed, but most information available suggests that major poor cognitive outcomes should not be attributed to this medication.
Journal ArticleDOI
Use of Antiepileptic Drugs During Pregnancy: Evolving Concepts
TL;DR: Knowledge of these key principles enhances the ability to make treatment recommendations with resultant improved maternal and child outcomes and further define the risk–benefit ratio across a variety of medications, dosing strategies, and neuropsychiatric disorders.
Journal ArticleDOI
Valproate-Induced Neurodevelopmental Deficits in Xenopus laevis Tadpoles
Eric J. James,Jenny Gu,Carolina M Ramirez-Vizcarrondo,Mashfiq Hasan,Torrey L.S. Truszkowski,Yuqi Tan,Phouangmaly M. Oupravanh,Arseny S. Khakhalin,Arseny S. Khakhalin,Carlos D. Aizenman +9 more
TL;DR: The findings indicate that the effects of VPA are remarkably conserved across vertebrate species and that changes in neural circuitry resulting from abnormal developmental pruning can cascade into higher-level behavioral deficits.
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Searching for the gut microbial contributing factors to social behavior in rodent models of autism spectrum disorder
TL;DR: Investigation of intestinal microbiota and host social behavior will unveil any bidirectional communication between the gut and brain and provide alternative therapeutic targets for ASD.
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Social behavior, neuroimmune markers and glutamic acid decarboxylase levels in a rat model of valproic acid-induced autism.
TL;DR: The results indicate that developmental exposure to VPA affects the social behavior in rats by modulating the expression levels of social behavior-related genes and inflammatory mediators accompanied with changes in GABA enzyme in the hippocampus.
References
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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.
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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.
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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.