Ozkan Hilal, Cetinkaya Merih, Köksal Nilgün, Yapici Senay
Faculty of Medicine, Division of Neonatology, Department of Pediatrics, Uludag University, Bursa, Turkey.
J Matern Fetal Neonatal Med. 2011 Mar;24(3):521-4. doi: 10.3109/14767058.2010.501120.
Valproic acid (VPA) is a teratogenic drug used in pregnant women for the treatment of epilepsy and mood disorders. Fetal valproate syndrome (FVS) is characterized by a number of abnormalities associated with VPA exposure in utero including neural tube defects, congenital heart defects, limb defects, genitourinary defects, brain, eye and respiratory anomalies, and abdominal wall defects. Complex cardiac defect and trigonocephaly have rarely been reported and multicystic dysplastic kidney has never been detected in FVS. We here report a female infant who was born to a mother with a history of low-dose VPA monotherapy (250 mg/day) during pregnancy and who had presented with a combination of unilateral multicystic dysplastic kidney, multicomplex cardiac defect including severe coarctation of aorta, Ebstein anomaly, secundum atrial septal defect, mesocardia along with trigonocephaly due to metopic craniosynostosis, typical facial appearance and limb defects. To our knowledge, this is the first case presented with multicystic dysplastic kidney, complex cardiac defect, trigonocephaly and other limb and facial defects because of exposure to very low-dose VPA monotherapy (250 mg/day) in utero. We conclude that VPA must be used very cautiously in pregnant women even as monotherapy and in low doses to prevent major congenital defects.
丙戊酸（VPA）是一种致畸药物，用于治疗孕妇的癫痫和情绪障碍。胎儿丙戊酸综合征（FVS）的特征是与子宫内接触VPA相关的一系列异常，包括神经管缺陷、先天性心脏缺陷、肢体缺陷、泌尿生殖系统缺陷、脑、眼和呼吸异常以及腹壁缺陷。复杂心脏缺陷和三角头畸形很少被报道，多囊性发育不良肾在FVS中从未被检测到。我们在此报告一名女婴，其母亲在孕期有低剂量VPA单药治疗（250毫克/天）史，该女婴出现了单侧多囊性发育不良肾、复杂心脏缺陷（包括严重主动脉缩窄、埃布斯坦畸形、继发孔房间隔缺损、中位心）以及由于额缝早闭导致的三角头畸形、典型面部外观和肢体缺陷等多种异常。据我们所知，这是首例因子宫内接触极低剂量VPA单药治疗（250毫克/天）而出现多囊性发育不良肾、复杂心脏缺陷、三角头畸形以及其他肢体和面部缺陷的病例。我们得出结论，即使是单药治疗且低剂量使用，孕妇使用VPA时也必须极其谨慎，以预防重大先天性缺陷。
