ABSTRACT

Vitamin A and its bioactive metabolite, retinoic acid, are vital to mammalian embryogenesis. It has been well established through studies in animals that large doses of vitamin A and its related compounds are teratogenic. As many women of childbearing age are prescribed retinoids, concern regarding teratogenic effects has led to the implementation of registry and pregnancy prevention programs. The molecular pathways involved in retinoic acid-induced teratogenesis remain an area of active research. While all systemic retinoids are considered teratogenic, studies regarding the comparative teratogenicity of retinoids have suggested differences in teratogenic potential. While topical all-trans-retinoic acid has been shown to undergo minimal systemic absorption and negligibly increases endogenous levels, the question of whether topical retinoids are teratogenic has remained a subject of debate. The teratogenic effects of isotretinoin were well known from animal research, so Roche released the drug with warnings and brochures for patients.