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PEDIATRICS Vol. 103 No. 3 March 1999, pp. 588-593

The Effects of Valproate, Carbamazepine, and Oxcarbazepine on Growth and Sexual Maturation in Girls With Epilepsy

Received May 5, 1998; accepted Sep 8, 1998.

Johanna Rättyä*, Leena VainionpääDagger , Mikael KnipDagger , Peter Lanning§, and Jouko I. T. Isojärvi*

From the Departments of * Neurology, Dagger  Pediatrics, and § Radiology, University of Oulu, Oulu, Finland.

Objective.  Antiepileptic drugs (AEDs) have endocrine effects that may interfere with growth and sexual maturation in children. The aim of this study was to evaluate the effects of AEDs on growth and pubertal development in girls with epilepsy.

Study Design.  Forty girls taking valproate (VPA), 19 girls taking carbamazepine (CBZ), and 18 girls taking oxcarbazepine (OXC) for epilepsy and 49 healthy control girls participated in the study, which included a cross-sectional clinical examination when the girls were 8 to 18 years old and a longitudinal growth analysis from the age of 1 year.

Results.  VPA, CBZ, or OXC did not affect linear growth or pubertal development in girls with epilepsy. However, the patients taking VPA gained weight, and an increase in relative weight was seen in girls who started their medication before as well as during puberty. The body mass index of the VPA-treated girls (19.8 ± 4.8 kg/m2) was higher than that of the control girls (18.0 ± 2.5 kg/m2) at clinical examination. The weight of the girls taking CBZ or OXC for epilepsy was similar to that of the control girls. Plasma insulin-like growth factor-I (IGF-I) levels were higher in girls treated with CBZ and OXC than in the control girls, but AEDs did not affect fasting serum insulin, IGF-binding protein-1, or IGF-binding protein-3 concentrations in girls on VPA, CBZ, or OXC medication during the period of exposure (average 2.8, 4.1, and 1.9 years, respectively) in this study.

Conclusions.  AEDs do not seem to have any adverse effects on linear growth or sexual maturation in girls with epilepsy. VPA-related weight gain can be seen already in prepuberty and it is not associated with hyperinsulinemia in these young patients. The clinical significance of high circulating concentrations of IGF-I in patients taking CBZ or OXC remains to be defined.  Key words:  girls, epilepsy, antiepileptic drugs, growth, sexual maturation, insulin, insulin-like growth factor-I, insulin-like growth factor binding proteins -1 and -3.




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