Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism

Abstract

NTIEPILEPTIC DRUG EXPOsure during pregnancy has been associated with an increased risk for congenital malformations and delayed cognitive development in the offspring, 1-3 but little is known about the risk of other serious neuropsychiatric disorders. Autistic symptoms have been described in case series of children exposed in utero to valproic acid, 4-7 and it has been suggested that valproate given to animals during pregnancy may constitute an experimental model of autism. 8-10 Genes play a significant role in the risk of autism, and disease-related genes may be identified in up to 25% of children with autism. 11 However, a variety of environmental factors may increase the risk of autism, 12 and prenatal valproate exposure would be a modifiable environmental exposure. Autism spectrum disorders are characterized by social and communication difficulties and by stereotyped or repetitive behaviors and interests. 13 The autism spectrum disorders include childhood autism (autistic disorder), Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders. We analyzed the risks associated with all autism spec-For editorial comment see p 1730.

Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records

“…Exposure to valproate was identified via linkage to their mothers' records during pregnancy from the Danish Prescription Register, which holds information on all prescriptions filled since 1996. 61 The Danish study suggested a substantial increase in diagnoses of autism spectrum disorder (adjusted hazard ratios 2.9, 95% CI 1.7 to 4.9) as well as childhood autism (adjusted hazard ratios 5.2, 95% CI 2.7 to 10.0) in comparison with children of 'healthy mothers'. 61 The association persisted when comparisons were made with women who discontinued treatment before pregnancy.…”

“…An American study based on Florida Medicaid beneficiaries suggested that use of valproate in pregnancy has declined for women with epilepsy over the period 1999 -2009, but not for other indications 60 and a Danish registry study suggested that dispensing of lamotrigine has been sharply rising during pregnancy in the period 1996-2006 (the time period of the study). 61 Future investigations should monitor the impact of these guidelines on prescribing.…”

“…18,61,106 Thus, a Danish registry study 61 identified 655,615 children born from 1996 through to 2006, of which 5437 were identified with autism spectrum disorder, including 2067 with childhood autism. Exposure to valproate was identified via linkage to their mothers' records during pregnancy from the Danish Prescription Register, which holds information on all prescriptions filled since 1996.…”

Vitamin D deficiency and autism; a review on recent findings

“…Vitamin D enhances glutathione in the brain, proposing a role of the hormone in brain detoxification pathways (50,51). Depakote is associated with autism in children born of mothers taking this drug during pregnancy (52). Depakote is capable of reducing vitamin D values (53).…”

“…This hormone presents immunomodulation, neuroprotection and antiepileptic properties (47). Prenatal, postnatal and even and neonatal vitamin D supplementation is imperative for ordinary brain activities (47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). The noticeable rise in the frequency of autism across the last 20 years is due to an increase in medical cautions to avoid the sun exposure because of its increasing of skin cancers.…”