Hyperhomocysteinaemia in children receiving phenytoin and carbamazepine monotherapy: a cross-sectional observational study.
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.
Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Saravanan
S
Chandrasekaran
Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Sooraj
S
Patil
Unit of Pediatric Neurology and Neurodevelopment, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Renu
R
Suthar
Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Savita Verma
SV
Attri
Unit of Pediatric Neurology and Neurodevelopment, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Jitendra Kumar
JK
Sahu
Unit of Pediatric Neurology and Neurodevelopment, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Naveen
N
Sankhyan
Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Mini
M
Tageja
Chief unit of Pediatric Neurology and Neurodevelopment, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Pratibha
P
Singhi
D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D006801:Humans; D020138:Hyperhomocysteinemia / Q000139:chemically induced*; D008134:Long-Term Care; D008297:Male; D010672:Phenytoin / Q000009:adverse effects*; D014803:Vitamin B Complex / Q000627:therapeutic use
D000927:Anticonvulsants; D014803:Vitamin B Complex; D002220:Carbamazepine; D010672:Phenytoin; D005492:Folic Acid
Carbamazepine; Epilepsy; Folic Acid; Hyperhomocysteinemia; Phenytoin