Effect of sodium phenytoin concentration on neural tube development in the early stages of chicken embryo development.

Animal and human research has shown that anticonvulsants are teratogens and pose a risk of causing fetal malformations. In various studies, the teratogenic effects of sodium phenytoin (PTH) in several systems have been investigated. Toe and finger, renal, and even facial malformations have been described in the literature. However, there is debate about whether the true risk of teratogenesis is lower or higher than previously reported for PTH. There is also little published information on the effect of this agent on neural tube closure in an embryological model. In this study, 0.1 mL of three different concentrations of PTH solution (mg/mL: 1, 3, 5) or vehicle was applied under the embryonic disc of specific pathogen-free Leghorn chicken embryos after 24 hours' incubation. Incubation was continued until 72 hours of maturation. At 72 hours, all embryos were evaluated macroscopically and microscopically. There were serious neural tube closure defects in the embryos administered large amounts (0.5 mg) of PTH, but doses of 0.1 mg (subtherapeutic concentration for humans) and 0.3mg (therapeutic concentration for humans) produced no statistically significant defects (p=0.05). The difference between the defects in the high concentration group and the other three groups was statistically significant. In our study PTH administered in a strict concentration regimen produced a lower level of neural tube closure-related defects than previously reported.