Teratogenicity of sodium valproate

Abstract

The teratogenicity of the widely popular antiepileptic drug (AED) and mood stabiliser sodium valproate (also known as valproate, VPA) has been evidenced by previous research; however, these findings have often been limited by a small population sample of exposed women and a retrospective study design. Many factors contribute to the teratogenicity of VPA. These include the number of drugs that are co-administered, drug dosage, differences in maternal and/or infant metabolism, the gestational age of the fetus at exposure, and hereditary susceptibility. VPA has been associated with a variety of major and minor malformations, including a 20-fold increase in neural tube defects, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrinological disorders, limb defects, and autism. It has been suggested that polytherapy treatment in epileptic pregnant women increases the risk of teratogenicity in offspring. Furthermore, there is an established relationship between VPA dose and adverse outcome. Large single doses of VPA potentially cause high peak levels in the fetal serum resulting in deleterious effects. Currently there is an increase in the number of national and international pregnancy registries being formed in an effort to better identify the teratogenic effects of AEDs. These efforts hope to enhance our understanding of AEDs and their associated risks by addressing past study limitations.

Seizure Control by Derivatives of Medium Chain Fatty Acids Associated with the Ketogenic Diet Show Novel Branching-Point Structure for Enhanced Potency

“…Direct inhibition of HDAC by VPA (Göttlicher et al, 2001;Gurvich et al, 2004) is thought to give rise to teratogenicity (Koren et al, 2006;Jentink et al, 2010), causing a variety of major and minor malformations, including neural tube defects, Seizure Control by Medium Chain Fatty Acid Derivatives cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrinological disorders, limb defects, and autism (Alsdorf and Wyszynski, 2005). This biochemical activity provides a crucial side-effect profile to consider in the development of carboxylic acid-based antiepileptic drugs.…”

Epigenetic control of skull morphogenesis by histone deacetylase 8

“…The data from this and other class I Hdac knockout studies indicate that HDAC inhibitors might be teratogenic, and indeed, this has been demonstrated in rodent models (Menegola et al 2006). Craniofacial abnormalities have also been described in children born from mothers treated with the HDAC inhibitor valproic acid (Alsdorf and Wyszynski 2005).…”

Hamile yatan psikiyatrik hastaların teşhis ve tedavi değerlendirmesi

“…Although lithium and valproic acid have a teratogenic effect, in some studies it was seen that these substances did not increase the incidence of major malformations. The negative information previously existing about these drugs was not confirmed by later research (12,13).…”