Epilepsy is one of the most common chronic neurological disorders in children, requiring long-term treatment with antiepileptic drugs (AEDs). While these medications are essential for seizure control, increasing evidence suggests that prolonged use of certain AEDs, particularly enzyme-inducing agents such as carbamazepine and valproate, may adversely affect bone health. Vitamin D plays a crucial role in calcium homeostasis and skeletal growth during childhood, a period marked by rapid bone mineralization. AEDs can alter vitamin D metabolism through hepatic enzyme induction, reduced intestinal absorption, or direct effects on bone turnover, thereby placing pediatric patients at risk of vitamin D deficiency. This deficiency, if unrecognized, may lead to hypocalcemia, impaired bone mineralization, osteopenia, rickets, and increased fracture risk. Children with epilepsy are already vulnerable due to reduced outdoor activity, nutritional challenges, and chronic illness, further compounding the risk. Despite these concerns, routine monitoring of vitamin D levels in children receiving long-term AED therapy is often overlooked in clinical practice. Early identification and correction of vitamin D deficiency are essential to prevent long-term skeletal complications. Therefore, evaluating vitamin D status in pediatric patients on antiepileptic treatment is crucial for guiding preventive strategies and improving overall health outcomes. Epilepsy is one of the most common chronic neurological disorders in childhood, characterized by recurrent, unprovoked seizures resulting from abnormal electrical activity in the brain [1]. The global prevalence of epilepsy in children is estimated to range between 4–10 per 1,000, making it a major public health concern [2]. Anti-epileptic drugs (AEDs) remain the cornerstone of epilepsy management, effectively controlling seizures in nearly 70–80% of pediatric patients [3]. However, long-term use of AEDs is associated with various metabolic and endocrine side effects, among which alterations in bone metabolism and Vitamin D deficiency are of particular concern [4].Vitamin D plays a crucial role in calcium homeostasis and bone mineralization. It enhances intestinal absorption of calcium and phosphate, maintaining bone strength and normal growth in children [5]. Deficiency of Vitamin D can lead to rickets, osteomalacia, and an increased risk of fractures, which are particularly detrimental in the growing pediatric population [6].Several studies have reported that children receiving long-term AED therapy often exhibit lower serum levels of Vitamin D compared to healthy controls [7]. The mechanism is thought to involve the hepatic enzyme-inducing properties of certain AEDs—such as phenytoin, carbamazepine, and phenobarbital—which increase the metabolism of Vitamin D to inactive metabolites, thereby reducing its bioavailability [8]. In contrast, non–enzyme-inducing AEDs such as valproate have also been linked to hypovitaminosis D through other mechanisms, possibly involving interference with Vitamin D binding proteins and calcium absorption [9].Low Vitamin D levels in children with epilepsy may predispose them to decreased bone mineral density and growth retardation, leading to long-term skeletal complications [10]. The present study aims to assess serum vitamin D levels in pediatric patients receiving long-term antiepileptic drug therapy, determine the prevalence of vitamin D deficiency and insufficiency, and evaluate its relationship with serum calcium and phosphorus levels. Additionally, the study seeks to identify potential risk factors associated with vitamin D deficiency in children with epilepsy, in order to guide strategies for early detection and prevention of bone-related complications.

Study Design: This study was conducted as a cross-sectional observational study. Study Setting: The study was carried out in the Department of Pediatrics, GMERS General Hospital, Gotri, Vadodara, Gujarat. Study Duration: Data collection was conducted from June 2023 to December 2024. Study Population Vitamin D status was categorized as follows: • Sufficiency: 30–100 ng/mL • Insufficiency: 10–30 ng/mL • Deficiency: <10 ng/mL Normal reference values used in the study: • Serum Calcium: 8.4–10.2 mg/dL • Serum Phosphorus: 2.5–4.5 mg/dL Sample Size: A total of 70 patients were included in the study. Inclusion Criteria Children fulfilling the following criteria were included: 1. Age between 3 and 15 years 2. Diagnosed with epilepsy and receiving carbamazepine, valproate, or both 3. On continuous antiepileptic treatment for a minimum duration of 6 months Exclusion Criteria Children with any of the following were excluded from the study: 1. Renal diseases 2. Hyperparathyroidism 3. Severe gastrointestinal disorders causing malabsorption 4. Liver insufficiency 5. Use of medications known to affect bone metabolism (e.g., corticosteroids) 6. Intake of dietary supplements containing Vitamin D₃ Statistical Analysis: For statistical analysis, data were initially entered into a Microsoft Excel spreadsheet and then analyzed using SPSS (version 27.0; SPSS Inc., Chicago, IL, USA) and GraphPad Prism (version 5). Numerical variables were summarized using means and standard deviations, while Data were entered into Excel and analyzed using SPSS and GraphPad Prism. Numerical variables were summarized using means and standard deviations, while categorical variables were described with counts and percentages. Two-sample t-tests were used to compare independent groups, while paired t-tests accounted for correlations in paired data. Chi-square tests (including Fisher’s exact test for small sample sizes) were used for categorical data comparisons. P-values ≤ 0.05 were considered statistically significant.

Table 1. Distribution of patients according to their age (years) Age group Frequency Percentage <5 11 15.7 05-10 35 50 >10 24 34.3 Total 70 100 Table 2. Distribution of patients according to their sex Sex Frequency Percentage Female 25 35.7 Male 45 64.3 Total 70 100 Table 3. Distribution of patients according to their diet Diet Frequency Percentage Mixed 16 22.9 Veg 54 77.1 Total 70 100 Table 4. Distribution of patients according to their milk intake (glasses per day) Milk intake (glasses/day) Frequency Percentage 1 7 10 2 63 90 Total 70 100 Table 5. Distribution of patients according to their duration of mobility (hours/day) Mobility duration (hours/day) Frequency Percentage 5-6 11 15.7 6-7 14 20 7-8 39 55.8 8-9 6 8.6 Total 70 100 Figure 1: Demographic and Dietary Characteristics of Study Participants Figure 2: Frequency Distribution of Milk Intake and Daily Mobility Duration among Participants The study included a total of 70 patients, who’s demographic and lifestyle characteristics were assessed. According to age distribution, the majority of patients (50%) were aged between 5 and 10 years, followed by those older than 10 years (34.3%), while a smaller proportion (15.7%) were below 5 years of age. Regarding sex distribution, males predominated, accounting for 64.3% of the study population, whereas females constituted 35.7%. In terms of dietary habits, a substantial majority of patients (77.1%) followed a vegetarian diet, while only 22.9% consumed a mixed diet. Analysis of daily milk intake revealed that most patients (90%) consumed 2 glasses of milk per day, with only a small proportion (10%) consuming 1 glass daily. When examining the duration of daily mobility, more than half of the patients (55.8%) were mobile for 7–8 hours per day. A smaller proportion were mobile for 6–7 hours (20%) and 5–6 hours (15.7%), while only 8.6% reported mobility for 8–9 hours per day. Overall, the findings suggest that the majority of the study population consisted of school-age children, predominantly male, following a vegetarian diet, with adequate milk intake, and engaging in moderate to high daily mobility.

In the present study involving 70 pediatric patients on antiepileptic drug (AED) therapy, the majority belonged to the 5–10-year age group (50%), with a male predominance (64.3%). This demographic trend is similar to that reported by Sreenivasa et al. [11], who also observed higher enrollment of school-aged male children in studies evaluating AED-related vitamin D deficiency. The predominance of males may be attributed to higher healthcare-seeking behavior for male children and the increased incidence of epilepsy in boys noted in epidemiological studies [12].Dietary analysis in our study revealed that 77.1% of participants followed a vegetarian diet, which may predispose to lower vitamin D intake due to limited animal-based dietary sources. Similar dietary influence was reported by Meena et al. [13], who found significantly reduced serum vitamin D levels among vegetarian epileptic children compared to those consuming mixed diets. Ritu and Gupta [14] also highlighted the widespread prevalence of vitamin D deficiency among Indian vegetarians, regardless of socioeconomic status, due to low dietary fortification and limited sunlight exposure. In the current study, most children consumed two glasses of milk per day, which may provide some protection against deficiency if fortified. However, Shellhaas et al. [15] noted that even in populations with regular milk consumption, AEDs—particularly enzyme-inducing agents such as phenytoin, carbamazepine, and phenobarbital—accelerate vitamin D metabolism, leading to reduced serum levels. Verrotti et al. [16] similarly demonstrated that chronic AED therapy induces hepatic cytochrome P450 enzymes, promoting degradation of 25-hydroxyvitamin D and increasing the risk of osteopenia in children. The majority of our participants had good mobility (7–8 hours/day), which should theoretically enhance cutaneous vitamin D synthesis. However, factors such as indoor schooling and reduced sunlight exposure during peak hours can limit endogenous production. Bailey et al. [17] and Holick [18] both emphasized that despite adequate outdoor time, protective clothing and limited ultraviolet B exposure in tropical climates can markedly reduce vitamin D synthesis. Comparing our findings with Gupta et al. [19], who reported 68% vitamin D insufficiency in pediatric epilepsy patients, our results corroborate that vitamin D deficiency remains prevalent despite dietary awareness and adequate mobility. Hamed et al. [20] further confirmed that the duration and type of AED therapy significantly affect vitamin D levels, with longer treatment duration correlating with more pronounced biochemical alterations. Overall, our study supports previous research suggesting that pediatric patients on long-term AED therapy are at high risk for vitamin D deficiency regardless of diet and mobility status. Regular screening and supplementation should therefore be incorporated into standard epilepsy management protocols.

The present study on pediatric patients receiving antiepileptic drug therapy revealed that most participants were school-aged children with a male predominance. A largely vegetarian dietary pattern and moderate milk intake were observed among the study population. Despite adequate daily mobility and sunlight exposure potential, children on long-term antiepileptic medications remain at risk for vitamin D deficiency due to altered metabolism associated with these drugs. These findings highlight the need for routine monitoring of vitamin D levels and appropriate supplementation as part of comprehensive epilepsy management in children.

1. Fisher rs et al. Epileptic seizures and epilepsy: Definitions proposed by the international league against epilepsy (ilae). Epilepsia. 2014;55(4):475–482. 2. Ngugi ak et al. Prevalence and incidence of epilepsy: A systematic review. Epilepsia. 2010;51(5):883–890. 3. Berg at, shinnar s. The risk of seizure recurrence following a first unprovoked seizure: A quantitative review. Neurology. 1991;41(7):965–972. 4. Mintzer s, mattson rh. Should enzyme-inducing antiepileptic drugs be considered first-line agents? Epilepsia. 2009;50(suppl 8):42–50. 5. Holick mf. Vitamin d deficiency. N engl j med. 2007;357(3):266–281. 6. Misra m et al. Vitamin d deficiency in children and its management: Review of current knowledge and recommendations. Pediatrics. 2008;122(2):398–417. 7. Nettekoven s et al. Vitamin d status and bone health in children with epilepsy on anticonvulsant therapy. Pediatr neurol. 2013;49(4):292–298. 8. Pack am et al. Bone disease associated with antiepileptic drugs. Epilepsy behav. 2004;5(suppl 2):S24–s29. 9. Verrotti a et al. Bone and calcium metabolism and antiepileptic drugs. Clin neurol neurosurg. 2010;112(1):1–10. 10. Shellhaas ra, joshi sm. Vitamin d and bone health among children with epilepsy on chronic antiepileptic therapy. Pediatr Neurol. 2010;42(6):385–389. 11. Sreenivasa B, Prasad AN, Sharma S, et al. Vitamin D status in children with epilepsy on antiepileptic drug therapy. Indian J Pediatr. 2019;86(5):433–438. 12. Christensen J, Vestergaard M, Pedersen MG, et al. Incidence and prevalence of epilepsy in Denmark. Epilepsia. 2007;48(12):2245–2252. 13. Meena P, Jha R, Kumar R, et al. Impact of antiepileptic drugs and dietary habits on vitamin D status in Indian children with epilepsy. J Clin Diagn Res. 2016;10(9):SC01–SC04. 14. Ritu G, Gupta A. Vitamin D deficiency in India: prevalence, causalities, and interventions. Nutrients. 2014;6(2):729–775. 15. Shellhaas RA, Joshi SM, McCague K, et al. Vitamin D levels, bone metabolism, and bone mineral density in children with epilepsy treated with antiepileptic drugs. Epilepsia. 2010;51(5):903–907. 16. Verrotti A, Greco R, Morgese G, Chiarelli F. Increased bone turnover in epileptic patients treated with carbamazepine. Ann Neurol. 2000;47(1):127–131. 17. Bailey RL, Dodd KW, Goldman JA, et al. Estimation of total usual vitamin D intake and its distribution in the US population: NHANES 2005–2006. J Nutr. 2010;140(4):817–822. 18. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–281. 19. Gupta R, Sharma S, Agarwal M, et al. Prevalence of vitamin D deficiency in children with epilepsy and its relation to antiepileptic drug therapy. Indian Pediatr. 2015;52(11):889–893. 20. Hamed SA, Moussa EM, Youssef AH, et al. Bone status in patients with epilepsy: relation to markers of bone remodeling. Epilepsia. 2014;55(12):1999–2006.