Effect of Folic Acid Supplementation on Seizure Control in Epileptic Children Receiving Long Term Antiepileptic Therapy
To evaluate the effect of folic acid supplementation on seizure control in folate deficient children receiving long term antiepileptic therapy.
In a prospective interventional study, 140 children between age group 6 mo to 180 mo fulfilling the inclusion criteria were enrolled in study group, from October 2015 through November 2016. On the basis of serum folate, study group was divided into two subgroups by non randomization: Group A (<10 ng/ml) given folic acid supplementation for 3 mo and Group B (>10 ng/ml) was not supplemented. Response to folic acid supplementation in group A was compared with group B in terms of change in blood folate levels, frequency and duration of seizures after three months.
Mean age of study group was 73.58 ± 46.89 mo (72.14% boys and 27.85% girls). 67.85% children were in group A and 32.14% in group B. On 3 mo follow up, children supplemented with folic acid (Group A) had significant fall in mean seizure frequency while in non-supplemented children (Group B), no significant change was seen (p value <0.05). Similar reduction in duration of seizure episode was seen in group A as compared to group B. Serum and RBC folate levels improved from baseline in group A, while in group B there was significant fall in folate levels.
Folate deficiency is common in epileptic children on long term antiepileptic drugs (AEDs), contributes to poor seizure control and should be considered in the etiologic differentials of drug resistant epilepsy. Folate supplementation improves seizure control in these children.
KeywordsChildhood epilepsy Folic acid Seizure Refractory
The authors thank Dr. Pramod Sharma, Head of the Department, Dr. S. N. Medical College, Jodhpur for his support and guidance.
BD and MP conceived and designed the study. BD, MP, PD,VP, KC, AP, SS and DP reviewed the literature, analyzed and interpreted data, drafted and prepared the manuscript. MP will act as the guarantor of the study. The final manuscript was approved by all authors.
Compliance with Ethical Standards
Conflict of Interest
- 5.Nayyar AS, Nataraju B, Subhas GT. Phenytoin-folate interactions : how far is safe folate supplementation in phenytoin treated epileptic patients? J Appl Pharm Sci. 2012;02:230–5.Google Scholar
- 9.Ramaekers VT, Sequeira JM, Blau N, Quadros EV. A milk-free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome. Dev Med Child Neurol. 2008;50:346–52.Google Scholar
- 11.World Health Organization (2012). Serum and red blood cell folate concentrations for assessing folate status in populations. Vitamin and Mineral Nutrition Information System. Geneva: World Health Organization; Available at: http://apps.who.int/iris/bitstream/10665/75584/1/WHO_NMH_NHD_EPG_12.1_eng.pdf. Accessed 15 Jan 2013.
- 14.Karabiber H, Sonmezgoz E, Ozerol E, Yakinci C, Otlu B, Yologlu S. Effects of valproate and carbamazepine on serum levels of homocysteine, vitamin B12, and folic acid. Brain Dev. 2003;25:113–5.Google Scholar
- 15.Mohamad A. Mikati, Hani AJ. Seizure in childhood, 1st South Asia ed. South Asia: Reed Elsevier India Pvt. Ltd.; 2016.Google Scholar
- 16.Pérez-Dueñas B, Ormazábal A, Toma C, et al. Cerebral folate deficiency syndromes in childhood: clinical, analytical, and etiologic aspects. Arch Neurol. 2011;68:615–21.Google Scholar
- 17.Opladen T, Blau N, Ramaekers VT. Effect of antiepileptic drugs and reactive oxygen species on folate receptor 1 (FOLR1)-dependent 5-methyltetrahydrofolate transport. Mol Genet Metabol. 2010;101:48–54.Google Scholar
- 19.Eldeen ON, Eldayem SMA, Shatla RH, Omara NA, Elgammal SS. Homocysteine, folic acid and vitamin B12 levels in serum of epileptic children. Egyptian J Med Hum Genet. 2012;13:275–80.Google Scholar
- 20.Geda G, Caksen H, Icagasioglu D. Serum lipids, vitamin B12 and folic acid levels in children receiving long-term valproate therapy. Acta Neurol Belg. 2002;102:122–6.Google Scholar
- 21.Huemer M, Ausserer B, Graninger G, et al. Hyperhomocysteinemia in children treated with antiepileptic drugs is normalized by folic acid supplementation. Epilepsia. 2005;46:1677-83.Google Scholar