Risks of In Utero Exposure to Valproate

Abstract

Antiepileptic medications are among the most commonly prescribed teratogenic drugs among women of childbearing potential. However, determining the exact number of women of childbearing age exposed to antiepileptic medications is difficult. One estimate, based on data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, suggests that from 2005-2007, there were 7 900 000 annual prescriptions for antiepileptic medications among girls and women aged 15 to 44 years, including 926 000 for valproate (12% of all antiepileptic medication prescriptions, irrespective of indication). 1 For those treated for epilepsy or seizures, there were 989 000 annual prescriptions, of which 177 000 were for valproate (18% of all prescriptions of antiepileptic medications for epilepsy or seizures). 1

Smell of autism: Synthetic fragrances and cause for allergies, asthma, cancer and autism

“…We hypothesize that one of the major reasons for the alarming rise in autism and autism spectrum disorder is the rise in use of fragrances 2 . It should be noted that autism used to be a relatively rare diseases at the turn of the 20th century [2][3][4][5][6][22][23][24] , but it has now been found that 1 out 88 children is suffering from ASD; again, this may be an underestimate. Since a neonate's brain is still developing after birth, we should expect a rise in other neurological but related conditions (e.g.…”

“…Since a neonate's brain is still developing after birth, we should expect a rise in other neurological but related conditions (e.g. attention de icit hyperactive disorder [ADHD], regressive autism; for example, a child is born normal but begins to show signs of autism after 18 months or later) [21][22][23][24] . ASD is a developmental condition characterized by de icits in social interaction, verbal and nonverbal communication and obsessive/stereotyped patterns of behaviour.…”

Using a mouse model to investigate male bias in autism spectrum disorder incidence.

“…Valproic acid (aka 2-propylpentanoic acid, valproate, or VPA), used both to treat epilepsy and as a mood stabilizer in those with bipolar disorder (Roullet, Lai, & Foster, 2013), is a known teratogen, with multiple pregnancy registries confirming an increased risk of major congenital malformations and correlations to reduced cognitive abilities following fetal exposure (Meador & Loring, 2013 and childhood autism (absolute risk, 2.50%; adjusted hazard ratio, 5.2 [95% CI, 2.7-10.0]) among the 508 children exposed to VPA (Christensen et al, 2013). Given the connection between ASD and epilepsy (reported in approximately 1/3 of autism cases) (Muhle et al, 2004;Tuchman, Cuccaro, & Alessandri, 2010), it is noteworthy that the increased risk remained significant after adjusting for parental psychiatric disease and epilepsy (Christensen et al, 2013;Meador & Loring, 2013).…”

“…Given the connection between ASD and epilepsy (reported in approximately 1/3 of autism cases) (Muhle et al, 2004;Tuchman, Cuccaro, & Alessandri, 2010), it is noteworthy that the increased risk remained significant after adjusting for parental psychiatric disease and epilepsy (Christensen et al, 2013;Meador & Loring, 2013).…”

“…Fetal exposure to valproic acid (VPA, 2-propyl-pentanoic acid), a drug used in the treatment of epilepsy and bipolar disorder (Roullet et al, 2013), was found to increase risk of major congenital malformations and reduce cognitive abilities (Meador & Loring, 2013), as well as increase risk of ASD (Christensen et al, 2013). VPA acts to increase gamma-aminobutyric acid synthesis and availability (Dufour-Rainfray et al, 2010;Loscher, 1999) and as a histone deacetylase inhibitor, providing a mechanism to influence gene expression (Dufour-Rainfray et al, 2010).…”