Morphological Aspects of Diazepam Induced Teratogenicity in Rats

Abstract

This study was conducted to determine the adverse effects of diazepam on morphology of art embryos. Pregnant rats were administered 0.14mg per kg body weight of diazepam, (therapeutic dose) intraperitoncally during different periods of pregnancy and 280mg per kg body weight (high dose) during the period of organogenesis. Adverse effects observed on the fetuses with therapeutic dose were reduction in number (20%), subdermal haemorrhages (20-25%) and omphalocoele (3%). There was significant reduction in weight and crown-rump length (p>0.05) with the high dose, overall malformation rate was 9.76%, anomalies of thyroid gland (5.6%), cleft lip (2.46%) and digital defects (1.6%) were noted. Reduction in weight and crown rump length was statistically more significant than the therapeutic dose (p>0.01). In addition to increased severity of these adverse effects, maternal mortality (25-50%) was also encountered with high dose in various subgroups. We conclude that as the adverse effects of diazepam were statistically significant, not only with the high dose but also with the therapeutic dose, therefore the possible risk of teratogenesis should be carefully weighted against the therapeutic dose, prescribing this drug in women of child bearing age, specially during pregnancy.