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孕期暴露于霉酚酸酯导致新生儿先天性食管闭锁和小耳畸形:一例报告及文献复习

Congenital Esophageal Atresia and Microtia in a Newborn Secondary to Mycophenolate Mofetil Exposure During Pregnancy: A Case Report and Review of the Literature.

作者信息

Alsebayel Musaed Mohammed, Abaalkhail Faisal Abdulrahman, Alsebayel Faisal Mohammed, Alissa Dema A, Al-Jedai Ahmed Hamdan, Elsiesy Hussien

机构信息

College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

Department of Liver and Small Bowel Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

出版信息

Am J Case Rep. 2018 May 3;19:523-526. doi: 10.12659/AJCR.908433.

Abstract

BACKGROUND Mycophenolate mofetil (MMF) is one of the most commonly prescribed drugs to prevent organ transplant rejection in combination with calcineurin inhibitors and steroids. It has a different toxicity profile than tacrolimus and cyclosporine.  Gastrointestinal tract disturbances are the most common adverse effects. The use of MMF in pregnant women, however, holds great risk of miscarriage and fetal development defects such as external ear malformation, ocular anomalies, cleft lip and palate, and abnormality of distal limbs, heart, esophagus, and kidneys. Based on post-marketing studies, its pregnancy category was reclassified as category D by the US FDA in 2007. CASE REPORT A 20-year-old woman received a deceased-donor liver transplant for end-stage liver disease secondary to autoimmune hepatitis. She had 3 miscarriages while on MMF. In her fourth pregnancy she was exposed to MMF in the first trimester, which was stopped by week 20 of the pregnancy. Obstetric ultrasound suggested a cephalic presentation fetus with abdominal circumference. Her pregnancy resulted in an infant with tracheoesophageal fistula, esophageal atresia, and a bilateral ear canal atresia (microtia) with normal sensorineural conduction. There were no other congenital abnormalities. Thoracoscopic ligation of fistula and thoracotomy with esophageal repair were performed and a bone-anchored hearing aid for conductive hearing loss was implanted. Here, we report a case of congenital esophageal atresia and microtia secondary to mycophenolate mofetil. CONCLUSIONS MMF should be avoided during pregnancy. Transplanted female patients of reproductive age should receive appropriate counseling.

摘要

背景

霉酚酸酯(MMF)是与钙调神经磷酸酶抑制剂和类固醇联合使用以预防器官移植排斥反应时最常用的药物之一。它具有与他克莫司和环孢素不同的毒性特征。胃肠道紊乱是最常见的不良反应。然而,孕妇使用MMF存在很大的流产风险以及胎儿发育缺陷风险,如外耳畸形、眼部异常、唇腭裂以及远端肢体、心脏、食管和肾脏异常。根据上市后研究,其妊娠分级在2007年被美国食品药品监督管理局重新分类为D级。病例报告:一名20岁女性因自身免疫性肝炎继发终末期肝病接受了已故供体肝脏移植。她在服用MMF期间有3次流产。在她第四次怀孕时,孕早期接触了MMF,在妊娠20周时停用。产科超声提示胎儿头先露,腹围正常。她的妊娠产下一名患有气管食管瘘、食管闭锁以及双侧耳道闭锁(小耳畸形)但感觉神经传导正常的婴儿。没有其他先天性异常。进行了胸腔镜下瘘管结扎和开胸食管修复手术,并植入了用于传导性听力损失的骨锚式助听器。在此,我们报告一例因霉酚酸酯导致先天性食管闭锁和小耳畸形的病例。结论:孕期应避免使用MMF。育龄期移植女性患者应接受适当的咨询。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92d3/5952718/a8aa2af53452/amjcaserep-19-523-g001.jpg

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