Vaux Keith K, Kahole Nathanial C O, Jones Kenneth Lyons
University of California San Diego, Department of Pediatrics, San Diego, California 92103-8446, USA.
Birth Defects Res A Clin Mol Teratol. 2003 Jun;67(6):403-8. doi: 10.1002/bdra.10060.
Cyclophosphamide (CP) is an alkylating agent primarily used for the treatment of autoimmune disease and cancer. The purpose of this article is two-fold: first, to indicate that CP is a recognized human teratogen based on the features seen in a child prenatally exposed to this agent, as well as features seen in the previously reported cases; second, to suggest a common pathway to explain the similarity in the pattern of malformation seen in infants prenatally exposed to CP, in infants prenatally exposed to methotrexate (MTX), and in infants prenatally exposed to cytosine arabinoside (CA).
Case report and review of the literature of an infant prenatally exposed to CP during the first trimester with a specific pattern of malformation. Features are compared to seven previous reports.
A common pattern of malformation is delineated including growth deficiency, hypoplasia of the calvarial and facial bones, and oligodactyly.
The finding of a similar pattern of malformation among eight infants prenatally exposed to CP suggests that CP is a human teratogen. MTX and CA produce similar patterns of malformation in prenatally exposed infants despite very different pharmocologic profiles and metabolism. We speculate that the phenotype is a consequence of apoptosis in certain cells which are susceptible to the effects of the teratogen at specific stages of development.
环磷酰胺（CP）是一种烷化剂，主要用于治疗自身免疫性疾病和癌症。本文目的有两个：其一，基于产前接触该药物的一名儿童所表现出的特征以及先前报道病例中的特征，表明CP是一种公认的人类致畸剂；其二，提出一条共同途径，用以解释产前接触CP的婴儿、产前接触甲氨蝶呤（MTX）的婴儿以及产前接触阿糖胞苷（CA）的婴儿中所见到的畸形模式的相似性。
对一名在孕早期产前接触CP且具有特定畸形模式的婴儿进行病例报告及文献回顾。将其特征与之前的七份报告进行比较。
描绘出一种常见的畸形模式，包括生长发育迟缓、颅骨和面部骨骼发育不全以及多指（趾）畸形。
在八名产前接触CP的婴儿中发现相似的畸形模式表明CP是一种人类致畸剂。尽管MTX和CA的药理特性及代谢情况差异很大，但它们在产前接触的婴儿中会产生相似的畸形模式。我们推测这种表型是某些细胞在发育特定阶段易受致畸剂影响而发生凋亡的结果。
