RETINOIC ACID EMBRYOPATHY
RETINOIC ACID EMBRYOPATHY
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DOI：
10.1056/nejm198510033131401
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发表时间：
1985-01-01
影响因子：
158.5
通讯作者：
SUN, SC
中科院分区：
文献类型：
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作者：
LAMMER, EJ;CHEN, DT;SUN, SC
众所周知，维甲酸是维生素A的类似物，在实验室动物中具有致畸作用，最近在一些临床病例报告中也发现了这一点。为了研究这种药物对人类的致畸性，我们调查了154例胎儿暴露于异维A酸（一种用于治疗严重顽固性囊性痤疮的维甲酸）的人类妊娠。结果为95例选择性流产，26例无严重畸形的婴儿，12例自然流产，21例畸形婴儿。对154例妊娠中的36例进行了前瞻性观察。该队列的结局为8例自然流产，23例正常婴儿和5例畸形婴儿。暴露于异维甲酸与一组选定的主要畸形的异常高的相对风险相关（相对风险= 25.6; 95%置信区间，11.4至57.5）。在21例畸形儿中，我们发现了一种特征性的畸形模式，涉及颅面、心脏、胸腺和中枢神经系统结构。畸形包括小耳畸形/无耳畸形（15例）、小颌畸形（6例）、腭裂（3例）、圆锥干心脏缺陷和弓状动脉畸形（8例）、胸腺缺陷（7例）、视网膜或视神经异常（4例）和中枢神经系统畸形（18例）。畸形的模式非常相似，在动物研究中产生的类维生素A致畸。异维A酸致畸作用的主要机制可能是对头神经嵴细胞活性的有害影响，导致观察到的颅面、心脏和胸腺畸形。
Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively. The outcomes in this cohort were 8 spontaneous abortions, 23 normal infants, and 5 malformed infants. Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5). Among the 21 malformed infants we found a characteristic pattern of malformation involving craniofacial, cardiac, thymic, and central nervous system structures. The malformations included microtia/anotia (15 infants), micrognathia (6), cleft palate (3), conotruncal heart defects and aortic-arch abnormalities (8), thymic defects (7), retinal or optic-nerve abnormalities (4), and central nervous system malformations (18). The pattern of malformation closely resembled that produced in animal studies of retinoid teratogenesis. It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations.