European Journal of Cardiovascular Medicine

Epilepsy is one of the most common neurological disorders in childhood, characterized by recurrent unprovoked seizures. Long-term use of anti-epileptic drugs (AEDs), especially enzyme-inducing agents such as phenytoin, carbamazepine, and phenobarbital, has been associated with vitamin D deficiency due to increased hepatic metabolism.(1) (2)Vitamin D is crucial for bone health and calcium-phosphate balance, and its deficiency may lead to osteopenia, osteoporosis, or rickets.(3) The current study is to assess the possible metabolic impact of long-term treatment.

AIMS AND OBJECTIVES OF THE STUDY

• To determine the serum vitamin D levels in children with first episode of unprovoked seizures in the age group 2-18 years, started on antiepileptic drug therapy.
• To compare the serum vitamin D levels between 2-18 years of age children requiring antiepileptics in first episode of unprovoked seizures and children on antiepileptics for seizure disorder for more than 12 months.

This cross-sectional comparative study was conducted in the Department of Paediatrics, Hassan Institute of Medical Sciences, Karnataka. A total of 100 children aged 2–18 years were included: Group A (first-episode unprovoked seizures) and Group B (on AED therapy for >12 months). Children with cerebral palsy, renal or hepatic disease, or known disorders of vitamin D metabolism were excluded. Serum vitamin D, calcium, phosphorus, and alkaline phosphatase (ALP) levels were measured using standard biochemical methods. Data were analyzed using SPSS software with t-tests and chi-square tests applied. Significance was set at p<0.05.

The study population included 55% males and 45% females, with a mean age of 9.1 ± 5.0 years. There were no significant differences in age, gender, BMI, or vital parameters between the groups. Mean serum vitamin D levels were comparable (Group A: 30.28 ± 5.94 ng/mL; Group B: 31.00 ± 6.15 ng/mL; p=0.55). Serum calcium, phosphorus, and ALP values showed no significant difference. Levetiracetam was the most prescribed AED in Group A (82%), while phenytoin predominated in Group B (84%). Total leukocyte count was significantly higher in Group A (p=0.001), indicating postictal physiological stress. No other laboratory parameters differed significantly.

Table 1: Comparison of Bone Metabolism Markers

Graph 1: Comparison of Bone Metabolism Markers between both groups.

Table 2: Differential Leukocyte Count

Graph 2: Differential Leukocyte Count comparison showing relative distribution of cell types in both groups.

This study found no significant association between long-term AED therapy and reduced serum vitamin D levels in children. Although earlier studies have reported hypovitaminosis D in patients using enzyme-inducing AEDs, regional factors such as sunlight exposure, diet, and supplementation practices may mitigate these effects. The findings are similar to  Ala-Houhala et al(5). and Ginige et al(6)., who found no significant vitamin D depletion with AED use. The elevated leukocyte count in first-episode seizure patients likely reflects a transient stress response rather than a chronic metabolic effect. Regular monitoring of vitamin D remains advisable, particularly in children on long-term polytherapy or those with limited sunlight exposure.

Long-term AED therapy did not significantly affect serum vitamin D or bone metabolism markers in this study. Current AED regimens appear metabolically safe in pediatric populations, though continued monitoring for vitamin D deficiency is recommended for optimal bone health and seizure control.

1. Offermann G, Pinto V, Kruse R. Antiepileptic drugs and vitamin D supplementation. Epilepsia. 1979;20(1):3–15.

2. Fong CY et al. Prevalence and risk factors for vitamin D deficiency in children with epilepsy. Epilepsy Res. 2014;108(8):1352–1356.

3. Yildiz E et al. Potential risk factors for vitamin D levels in long-term AED use. Acta Neurol Belg. 2017;117:447–453.

4. Dong N et al. Serum vitamin D levels in children with epilepsy: comparison with healthy controls. Front Neurol. 2022;13:876543.

5. Ala-Houhala M et al. Vitamin D metabolites in epileptic patients on long-term anticonvulsant therapy. Eur J Pediatr. 1988;147:573–576.

6. Ginige N, de Silva KH, Wanigasinghe JK, Gunawardane NS, Munasinghe TJ. Effects of long term anti epileptic drugs on serum vitamin D levels and bone profile in a cohort of Sri Lankan children. International journal of pediatric endocrinology. 2015 Jan 1;2015(Suppl 1):P66.