The Fetal Trimethadione Syndrome

Abstract

We describe a family in which seven pregnancies resulted in four infants who died and in three abortions. During these pregnancies the mother took trimethadione (Tridione), as well as other anticonvulsants. Two normal children were born after treatment with all medications were stopped. There have now been 53 reported pregnancies in which the fetuses were exposed to trimethadione or paramethadione; 48 (87%) resulted in fetal loss or a child born with congenital malformations. The most common defects include malformed ears, cleft palate, cardiac defects, urogenital malformations, and skeletal abnormalities. Delayed mental and physical development were also seen. These findings constitute a clinical entity termed the fetal trimethadione syndrome. The malformation rate is believed to be due to the teratogenic effects of trimethadione. Physicians need to be aware of the danger of trimethadione and related drugs during pregnancy and should withhold these medications during this period.

Implementing a trilineage differentiation in the ReproTracker assay for improved teratogenicity assessment

“…Although teratogenic effects of methanol have been detected in rodent studies ( Hansen et al, 2005 ), this compound is not considered to be a reproductive or developmental toxicant in humans due to insufficient human data ( NTP-CERHR Expert Panel et al, 2004 ). Trimethadione, an anticonvulsant, has been shown to be highly teratogenic in mice ( Brown et al, 1979 ) and is a suspected human teratogen ( Feldman et al, 1977 ; Midha et al, 1979 ).…”

Depolarization induces calcium-dependent BMP4 release from mouse embryonic palate mesenchyme

“…Similarly, pentobarbital use during the first trimester increases incidence of cleft lip/palate in humans and in rodents and blocks GABA A receptors, which are ligand-gated Cl - ion channels ( 19, 89 ). In addition, Trimethadione, which blocks voltage-dependent T-type Ca ## channels, significantly increases the incidence of cleft palate, ear defects, and limb defects in the children of women who took the medication during the first trimester of pregnancy ( 18, 90, 91 ). We identify many previously uncharacterized ion channels expressed within the palatal mesenchyme that are targets of Pharmacologics (Fig.…”

DDREL: From drug-drug relationships to drug repurposing

“…It is withdrawn from the market [89]. Trimethadione was one of the first drug used in in petit mal epilepsies, but later it was found teratogen [90, 91, 92]. The example shows the problem with the ATC categories.…”