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Hyperhomocysteinaemia in children receiving phenytoin and carbamazepine monotherapy: a cross-sectional observational study
  1. Saravanan Chandrasekaran1,
  2. Sooraj Patil1,
  3. Renu Suthar2,
  4. Savita Verma Attri1,
  5. Jitendra Kumar Sahu2,
  6. Naveen Sankhyan2,
  7. Mini Tageja1,
  8. Pratibha Singhi3
  1. 1Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
  2. 2Unit of Pediatric Neurology and Neurodevelopment, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
  3. 3Chief unit of Pediatric Neurology and Neurodevelopment, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India
  1. Correspondence to Dr Savita Verma Attri, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India; attrisavi{at}yahoo.co.in

Abstract

Objective Long-term therapy with phenytoin and carbamazepine is known to cause hyperhomocysteinaemia. We evaluated the prevalence of hyperhomocysteinaemia in North Indian children receiving phenytoin or carbamazepine monotherapy for >6 months duration and the effect of folic acid supplementation on plasma homocysteine.

Methods In this cross-sectional observational study we enrolled consecutive children aged 2–12 years with epilepsy who had received phenytoin or carbamazepine monotherapy for >6 months. Plasma total homocysteine, folic acid, vitamin B12 and antiepileptic drug concentrations were measured. Healthy age- and sex-matched controls were recruited. Children with homocysteine >10.4 µmol/L received folic acid supplementation for 1 month and homocysteine and folic acid concentrations were measured after 1 month follow-up.

Results A total of 112 children receiving antiepileptic monotherapy for >6 months were enrolled. Hyperhomocysteinaemia was present in 54 children (90%) receiving phenytoin, 45 children (90%) receiving carbamazepine therapy and 17 (34%) controls (p<0.05). Mean plasma homocysteine concentrations were significantly higher (18.9±10.2 vs 9.1±3 µmol/L) and serum folic acid concentrations (10.04±8.5 ng/ml vs 12.6±4.8 p<0.001) and vitamin B12 concentrations (365±155 pg/mL vs 474±332 pg/mL, p=0.02) were significantly lower in the study group compared with the control group. Duration of antiepileptic drug therapy correlated significantly with elevated homocysteine and reduced folic acid concentrations (p<0.05). Supplementation with folic acid for 1 month led to a reduction in plasma homocysteine concentrations in the study group (from 20.9±10.3 µmol/L to 14.2±8.2 µmol/L, p<0.05).

Conclusions Phenytoin or carbamazepine monotherapy for >6 months duration is associated with hyperhomocysteinaemia in 90% of North Indian children. Elevated homocysteine concentrations were normalised in these children with folic acid supplementation.

  • Phenytoin
  • Carbamazepine
  • Epilepsy
  • Hyperhomocysteinemia
  • Folic Acid

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Footnotes

  • Contributors SC and SP: helped in data collection. RS: Written manuscript, data interpretation and data analysis, and preparation of manuscript. SVA: concept and design of the study, critical review of the manuscript for important intellectual content and final approval of the version to be published. JKS: patient management, critical review of the manuscript for important intellectual content. NS: patient management, critical review of the manuscript for important intellectual content. MT: biochemical analysis of samples. PS: clinician-in-charge, critical review of manuscript for important intellectual content.

  • Competing interests None declared.

  • Ethics approval Ethics approval was obtained from the PGIMER Institute Ethic Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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