1043-3155 Pediatr Neurol Briefs pedneurbriefs Pediatr Neurol Briefs Pediatric Neurology Briefs Pediatr Neurol Briefs 2166-6482 1043-3155 2166-3155 Pediatric Neurology Briefs Publishers Chicago, IL, USA PNB-6-61-b 10.15844/pedneurbriefs-6-8-7 Seizure Disorders Neurology Pediatrics Nervous System Diseases Child Development Brain Diseases Neurosurgery Child Infant Valproate-Induced Pubertal Arrest http://orcid.org/0000-0002-0173-7931 Millichap J. Gordon MD 1 2 * Division of Neurology, Children's Memorial Hospital, Chicago, IL Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL Correspondence: Dr. J. Gordon Millichap, E-mail: jgmillichap@northwestern.edu 08 1992 01 07 2016 6 8 61 62 Copyright: © 1992 The Author(s) 1992 This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Pubertal arrest associated with valproic acid therapy

A 12-year-old girl with complex partial seizures who had pubertal arrest of both growth and secondary sexual development while receiving VPA is reported from the Department of Pediatrics, Wright State University, Dayton, OH and the University of Iowa, Iowa City, IA.

 Valproate Pubertal Arrest Fetal Spina Bifida

A 12-year-old girl with complex partial seizures who had pubertal arrest of both growth and secondary sexual development while receiving VPA is reported from the Department of Pediatrics, Wright State University, Dayton, OH and the University of Iowa, Iowa City, IA. She had received Depakote from 10 years 7 months of age in doses ranging from 750 mg/day (17 mg/kg/day) to 1,500 mg/day (36 mg/kg/day) and a maximum VPA level of 135.5 ug/dl. Her growth rate during treatment decreased to 1.9 cm/yr compared to 4.9 cm/yr prior to treatment. When treatment was discontinued, normal pubertal growth and maturation resumed with a growth rate of 10 cm/yr. Cranial MRI with gadolinium and CT were normal. [1]

COMMENT. The authors recommend that children and adolescents on VPA therapy should have height, weight and Tanner staging of genitalia and pubic hair assessed at each clinic visit to detect arrest of growth and development.

A causal association between maternal use of VPA and fetal spina bifida has been reported [2]. Of 261 pregnant women receiving antiepileptic drugs, 6.3% of fetuses with VPA exposure had spina bifida aperta, whereas other antiepileptic drugs were not implicated in this developmental abnormality. High serum levels of VPA in the mother may have increased the risk which might be diminished by reduction of the daily dose.

 Cook JS Bale JF Hoffman RP Pubertal arrest associated with valproic acid therapy Pediatr Neurol 1992 May-Jun 8 3 229 231 10.1016/0887-8994(92)90075-A 1622523 Omtzigt JGC Los FJ Grobbee DE Pijpers L Jahoda MG Brandenburg H The risk of spina bifida aperta after first-trimester exposure to valproate in a prenatal cohort Neurology 1992 Apr 42 4 Suppl 5 119 125 1574165