The impact of the use of antiepileptic drugs on the growth of children

Abstract

Background: This study investigated whether long-term treatment with antiepileptic drugs (AEDs) had negative effects on statural growth and serum calcium levels in children with epilepsy in Taiwan.

Methods: Children with epilepsy treated with one prescription of AEDs (monotherapy) for at least 1 year were selected. The AEDs included valproic acid (VPA; Deparkin) in 27 children (11 boys and 16 girls) aged 4-18 years, oxcarbazepine (Trileptal) in 30 children (15 boys and 15 girls) aged 5-18 years, topiramate (Topamax) in 19 children (10 boys and 9 girls) aged 6-18 years, and lamotrigine (Lamicta) in eight children (5 boys and 3 girls) aged 5-13 years. Patients with a history of febrile convulsions were selected as the controls.

Results: One year of VPA treatment significantly impaired the statural growth of pediatric patients with epilepsy (p < 0.005) compared with the control group. The underlying mechanism may have been due to the direct effect of VPA on the proliferation of growth plate chondrocytes rather than alterations of serum calcium.

Conclusions: These results raise serious concerns about the growth of pediatric epilepsy patients who use AEDs, and potentially the need to closely monitor growth in children with epilepsy and adolescents under AED treatment, especially VPA.

Figure 1

VPA significantly affected growth of children with epilepsy. Comparison of changes in body height among the control group and children with epilepsy treated for 1 year with AEDs, including VPA, OXA, TPM, and LTG. The bars represent means, and the whiskers represent standard errors. Significant differences (**, p < 0.005) were found between the control group and the group with VPA treatment.

Figure 2

AEDs did not affect the level of calcium in children with epilepsy. Comparison in the changes of serum total (A) and ionized (B) calcium concentration among the control group and children with epilepsy treated for 1 year with AED, including VPA, OXA, TPM, and LTG. The bars represent means, and the whiskers represent standard errors.

Figure 3

VPA significantly reduced the proliferation of rat growth-plate chondrocytes. The influence of vehicle (0.1% DMSO) and AEDs, including VPA, OXA, LEV, LTG, and TPM on chondrocytes of rat growth-plate proliferation in MEM:HAM-F12 (1 : 1) medium with 10% FBS, expressed as cell growth percentages. The mean values are presented on top of the bars with the standard error value. (**, p < 0.005).