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
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Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism.
Jakob Christensen,Therese Koops Grønborg,Merete Juul Sørensen,Diana Schendel,Erik T. Parner,Lars Pedersen,Mogens Vestergaard +6 more
TL;DR: Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy.
Journal ArticleDOI
The Changing Epidemiology of Autism Spectrum Disorders
Kristen Lyall,Lisa A. Croen,Julie L. Daniels,M. Daniele Fallin,Christine Ladd-Acosta,Brian K. Lee,Brian K. Lee,Bo Y. Park,Nathaniel W. Snyder,Diana Schendel,Diana Schendel,Heather E. Volk,Gayle C. Windham,Craig J. Newschaffer +13 more
TL;DR: Eviologic investigations focused on nongenetic factors have established advanced parental age and preterm birth as ASD risk factors, indicated that prenatal exposure to air pollution and short interpregnancy interval are potentialrisk factors, and suggested the need for further exploration of certain prenatal nutrients, metabolic conditions, and exposure to endocrine-disrupting chemicals.
Journal ArticleDOI
The consequences of refractory epilepsy and its treatment
Kenneth D. Laxer,Eugen Trinka,Lawrence J. Hirsch,Fernando Cendes,John T. Langfitt,Norman Delanty,Trevor Resnick,Selim R. Benbadis +7 more
TL;DR: This critical review summarizes known risks associated with refractory epilepsy, provides practical clinical recommendations, and indicates areas for future research.
Journal ArticleDOI
The bowel and beyond: the enteric nervous system in neurological disorders
Meenakshi Rao,Michael D. Gershon +1 more
TL;DR: Evidence for ENS dysfunction is reviewed in the aetiopathogenesis of autism spectrum disorder, amyotrophic lateral sclerosis, transmissible spongiform encephalopathies, Parkinson disease and Alzheimer disease, and animal models suggest that common pathophysiological mechanisms account for the frequency of gastrointestinal comorbidity in these conditions.
Journal ArticleDOI
The valproic acid-induced rodent model of autism.
TL;DR: The VPA model provides a valuable tool to investigate the neurobiology underlying autistic behavior and to screen for novel therapeutics, highlighting its importance and reliability as an environmentally-induced animal model of autism.
References
More filters
Journal ArticleDOI
Maternal alcohol use disorder and offspring ADHD: disentangling genetic and environmental effects using a children-of-twins design.
Valerie S. Knopik,Andrew C. Heath,Theodore Jacob,Wendy S. Slutske,Kathleen K. Bucholz,Pamela A. F. Madden,Mary Waldron,Nicholas G. Martin +7 more
TL;DR: Offspring of twins with a history of AUD, as well as offspring of non-AUD monozygotic twins whose co-twin had AUD, were significantly more likely to exhibit ADHD than offspring of controls, consistent with a genetic explanation for the association between maternal AUD and increased offspring risk of ADHD.
Journal ArticleDOI
A Clinical Study of 57 Children With Fetal Anticonvulsant Syndromes
Susan J Moore,Peter D. Turnpenny,A. Quinn,S. Glover,David J. Lloyd,Tara Montgomery,John Dean +6 more
TL;DR: Speech delay, joint laxity, glue ear, and myopia are common in the fetal anticonvulsant syndromes and autistic features and hyperactivity form part of the behavioural phenotype.
Journal ArticleDOI
Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy.
Frank J.E. Vajda,Terence J. O'Brien,Alison A. Hitchcock,Janet Graham,Mark J. Cook,Cecilie M. Lander,Mervyn J. Eadie +6 more
TL;DR: There is a dose-effect relationship for FM and exposure to VPA during the first trimester of pregnancy, with higher doses of VPA associated with a significantly greater risk than with lower doses or with other AEDs.
Journal ArticleDOI
A male with fetal valproate syndrome and autism.
P G Williams,Joseph H. Hersh +1 more
TL;DR: A patient who has a clinical phenotype compatible with both FVS and autism is reported on, suggesting that a relation between this known teratogen and autism may exist.
Journal ArticleDOI
Foetal Antiepileptic Drug Exposure and Verbal versus Non-Verbal Abilities at Three Years of Age.
Kimford J. Meador,Gus A. Baker,Nancy Browning,Morris J. Cohen,Jill Clayton-Smith,Laura A. Kalayjian,Andres M. Kanner,Joyce Liporace,Page B. Pennell,Michael Privitera,David W. Loring +10 more
TL;DR: A dose-dependent relationship is present for both lower verbal and non-verbal abilities with valproate and for lower verbal abilities with carbamazepine and preconceptional folate may improve cognitive outcomes.