• Valproate sodium has been implicated in the production of spina bifida in humans; this article reports an animal model. Teratogenicity of valproate sodium was studied by oral administration of single doses of 225, 340, and 560 mg/kg to pregnant CD-1 mice on days 7 through 12 of gestation. All fetuses were examined on day 17. Treated fetuses demonstrated external malformations and a decrease in weight. The incidence of malformations was greater at the higher dosage levels of 340 mg/kg and 560 mg/kg, with a predominance of exencephaly, open eyelids, and gross skeletal defects. There was a significant increase in the resorption rate of the fetuses in the treated groups. There was also a significant increase in the malformations observed per litter and per live fetus population when compared with controls.
Ruth B. Paulson, Martha E. Sucheston, Thomas G. Hayes, George W. Paulson. Teratogenic Effects of Valproate in the CD-1 Mouse Fetus. Arch Neurol. 1985;42(10):980–983. doi:10.1001/archneur.1985.04060090062015