Piggott Kurt D, Sorbello Andrea, Riddle Elise, DeCampli William
Congenital Heart Institute, Arnold Palmer Hospital for Children, 50 W. Sturtevant St., Orlando, FL 32806, USA.
Pediatr Cardiol. 2011 Apr;32(4):518-20. doi: 10.1007/s00246-011-9913-z. Epub 2011 Feb 17.
Folate antagonist are chemotherapeutic agents used in many neoplastic, autoimmune, and inflammatory disorders. The first suggestions that folic acid antagonists were teratogenic in humans were based on reports of failed terminations in mothers given aminopterin in the first trimester. Newborns who survived after aminopterin exposure were noted for years to have defects of the neural tube, skull, or limbs. There is now a well-defined syndrome of congenital anomalies associated with the use of aminopterin. The aminopterin syndrome consists of cranial dysostosis, hypertelorism, anomalies of the external ears, micrognathia, limb anomalies, and cleft palate. The use of aminopterin has now fallen out of favor. Methotrexate is a folate antagonist that is now used more frequently. A similar pattern of malformations has been found in fetuses exposed to methotrexate. If used during pregnancy, it can cause congenital malformations or fetal death. A consistent association between methotrexate exposure and cardiac, renal, or gastrointestinal malformations has not been reported. We report two patients who presented with classic features of aminopterin syndrome combined with significant congenital cardiac malformations after first-trimester in utero methotrexate exposure. Both of these patients survived to undergo corrective cardiac surgery.
叶酸拮抗剂是用于多种肿瘤、自身免疫性和炎症性疾病的化疗药物。关于叶酸拮抗剂对人类具有致畸性的最初提示，是基于头三个月接受氨甲蝶呤治疗的母亲终止妊娠失败的报告。多年来，人们注意到暴露于氨甲蝶呤后存活下来的新生儿存在神经管、颅骨或四肢缺陷。现在有一种与使用氨甲蝶呤相关的明确的先天性异常综合征。氨甲蝶呤综合征包括颅骨发育不全、眼距过宽、外耳异常、小颌畸形、肢体异常和腭裂。如今，氨甲蝶呤已不再常用。甲氨蝶呤是一种叶酸拮抗剂，现在使用更为频繁。在暴露于甲氨蝶呤的胎儿中也发现了类似的畸形模式。如果在怀孕期间使用，它会导致先天性畸形或胎儿死亡。尚未有关于甲氨蝶呤暴露与心脏、肾脏或胃肠道畸形之间存在一致关联的报告。我们报告了两名患者，他们在孕期头三个月宫内暴露于甲氨蝶呤后，出现了氨甲蝶呤综合征的典型特征，并伴有严重的先天性心脏畸形。这两名患者均存活下来并接受了心脏矫正手术。
