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[维生素A及其衍生物的致畸作用]

[Teratogenic effects of vitamin A and its derivates].

作者信息

Guillonneau M, Jacqz-Aigrain E

机构信息

Unité de pharmacologie clinique, hôpital Robert-Debré, Paris, France.

出版信息

Arch Pediatr. 1997 Sep;4(9):867-74. doi: 10.1016/s0929-693x(97)88158-4.

Abstract

Retinoids, the synthetic derivates of vitamin A, have a key role on cellular differentiation and developmental tissue specificity. Their effects are mediated by nuclear receptors which transactivate homeobox genes. They are teratogenic to animals and they all induce similar malformations dependent on the dose and the duration of exposure. This is a review of the teratogenic effects of vitamin A and its synthetic derivates--isotretinoin, acitretine and topical retinoids--in humans. High dose vitamin A have a potent teratogenic effect and are therefore contra-indicated during pregnancy. Isotretinoin is responsible for a syndrome including malformations of the central nervous system, heart and thymus, together with craniofacial defects. The incidence rate is high and comparable to thalidomide (ie, 25%). This high teratogenic potency justifies a strict limitation of such a prescription in women susceptible to become pregnant. Acitretine, which replaces etretinate because of its long half life of 120 days, might also be teratogenic in humans. In addition, it may be back transformed into etretinate, thus contraindicating pregnancy for 2 years after withdrawal. Finally, despite a low percutaneous resorption, available data on the use of retinoids as 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 of their potent teratogenic effect.

摘要

维甲酸是维生素A的合成衍生物,在细胞分化和发育组织特异性方面发挥关键作用。它们的作用由激活同源框基因的核受体介导。它们对动物具有致畸性,并且根据剂量和暴露持续时间,都会诱发相似的畸形。本文综述了维生素A及其合成衍生物——异维甲酸、阿维A和外用维甲酸——对人类的致畸作用。高剂量维生素A具有强大的致畸作用,因此孕期禁用。异维甲酸会导致一种综合征,包括中枢神经系统、心脏和胸腺畸形,以及颅面缺陷。发病率很高,与沙利度胺相当(即25%)。这种高致畸性使得对易孕女性的此类处方必须严格限制。阿维A因其120天的长半衰期而取代了依曲替酯,在人类中也可能具有致畸性。此外,它可能会逆转化为依曲替酯,因此停药后2年内都应避免怀孕。最后,尽管外用维甲酸经皮吸收较少,但关于其使用的现有数据有限,因此不建议在孕期使用。尽管维甲酸对皮肤病有效,但由于其强大的致畸作用,育龄女性对其的使用非常有限。

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