TERATOGENICITY OF VITAMIN-A AND DERIVATES

Retinoids, the synthetic derivates of vitamin A, have a key role on ce llular differenciation and developmental tissue specificity. Their eff ects are mediated by nuclear receptors which transactivate homeobox ge nes. They are teratogenic to animals and they ail induce similar malfo rmations dependent on the dose and the duration of exposure. This is a review of the teratogenic effects of vitamin A and its synthetic deri vates - isotretinoin, acitretine and topical retinoids - in humans. Hi gh dose vitamin A have a potent teratogenic effect and are therefore c ontra-indicated during pregnancy. Isotretinoin is responsible for a sy ndrome including malformations of the central nervous system, heart an d thymus, together with craniofacial defects. The incidence rate is hi gh and comparable to thalidomide (ie, 25%). This high teratogenic pote ncy justifies a strict limitation of such a prescription in women susc eptible to became pregnant. Acitretin, which replaces etretinate becau se of its long half life of 120 days might also be teratogenic in huma ns. In addition, it may be back transformed into etretinate, thus cont raindicating pregnancy for 2 years after withdrawal. Finally despite a low percutaneous resorption, available data on the use of retinoids a s topicals are limited and their use during pregnancy is therefore not recommended. Although they are efficient in skin diseases, the use of retinoids in women of the child bearing age is very limited because o f their potent teratogenic effect.