Valproic acid effect on neural tube defects is not prevented by concomitant folic acid supplementation: Early chick embryo model pilot study.

BACKGROUND: Neural tube defect is one of the most prevalent congenital malformations and it involves a variety of malformations ranging from anencephaly to spina bifida. Folic acid supplementation during pregnancy is known to reduce risk of neural tube defects. Antiepileptic drugs have been associated with neural tube defects, one of which is valproic acid. Protective effect of folic acid on congenital malformations in patients using valproic acid or other antiepileptic medicines during pregnancy has not clearly been delineated uniformly in previous clinical series. In this experimental animal study of early chick embryo model, we would like to determine if there is any dose-response relationship between VA and NTDs and if there is any protective effect of FA on this relationship in early chick embryo period. METHODS: One hundred twenty-two fertile leghorn type chicken eggs were used in this study. Six groups, each of which composed of 20 fertilized eggs, were categorized as: group A-control, group B- folic acid, group C-low-dose valproic acid, group D-high-dose valproic acid, group E-low-dose valproic acid + folic acid, group F-high-dose valproic acid + folic acid. Eggs were hatched for 24 h and injected with destined solutions and hatched till 72th hour. RESULTS: No neural tube defect was observed in group A and B. High dose valproic acid led to significantly higher number of embryos with neural tube defects compared to low-dose valproic acid (p = 0.018). This significant difference was also present between low-dose and high dose valproic acid combined with folic acid (p = 0.031). When effect of folic acid was evaluated no significant difference observed between groups. CONCLUSIONS: Even though number of embryos with neural tube defects decreased with concomitant folic acid administration, this difference could not reach a statistical level. More experimental animal and large-scaled prospective clinical studies are in need to detect folic acid mechanism in inhibiting antiepileptic drugs, if any present.