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Neurology India
Medknow Publications on behalf of the Neurological Society of India
ISSN: 0028-3886 EISSN: 1998-4022
Vol. 54, Num. 1, 2006, pp. 47-47

Neurology India, Vol. 54, No. 1, January-March, 2006, pp. 47

Invited Comments

Invited Comments

Hospital for Children and Adolescents, Helsinki University Hospital, P.O.Box 280, 00029 HUS
Correspondence Address:Hospital for Children and Adolescents, Helsinki University Hospital, P.O.Box 280, 00029 HUS,

Code Number: ni06009

Related article: ni06009

An important study reporting the results of one-year follow-up in infants of mothers with epilepsy is published in this issue of Neurology India.[1] The authors enrolled 33 consequtive pregnancies of women all of whom had antiepileptic treatment. Thirty women (91%) participated in the study, together with 30 control women and their infants. Exposure data, including maternal drug treatment, seizures and pregnancy complication were prospectively collected from the first trimester. 18 (60%) of the mothers with epilepsy used phenytoin during pregnancy.

One major malformation (3%) was observed in the case group; this is well in line with what would be expected based on previous research on antiepileptic drug (AED) teratogenicity.[2] Malformation rates observed with prenatal phenytoin exposure have usually varied between 2-9%, depending partly on the definition of major malformation used in the study. Valproate exposure, especially in doses exceeding 1000 mg per day, seems to carry a higher malformation risk than other AEDs. Polytherapy appears to be more harmful than monotherapy.

The authors[1] observed a significant delay in locomotor function in phenytoin-exposed infants during the first year, but there was no impairment in reaching behavior and personal/social scores. Previous studies investigating early development in children of mothers with epilepsy have shown controversial results, but later catch-up development has often been reported for those who had subtle delays infancy. Prospective population-based studes have found no evidence that prenatal exposure to phenytoin[3] or to carbamazepine[4] would impair intelligence at preschool or school age. Prenatal cognitive effects of phenobarbital have been very little studied. Recent research has raised concern that prenatal valproate exposure may be harmful for verbal intelligence,[4],[5] but this needs to be explored by further prospective studies.

Despite the teratogenic risk, maintaining effective AED therapy is vital for both mother and child, as several case reports have described serious injury to the fetal brain after protolonged maternal convulsive seizures during pregnancy. Based on the present state of knowledge, teratogenicity can be minimized by using AED monotherapy whenever possible with lowest effective dose. Supplementing with folate may also be beneficial.[2]

Phenytoin exposure was associated to enlarged anterior fontanelle already at birth,[1] perhaps associated with drug-induced bone loss.[6] Although the case infants had normal intrauterine and neonatal growth, they gained significantly less weight, length and head circumference during their first year than control infants.[1] These findings highlight the importance of encouraging breast feeding and maintaining good nutritional status during and after pregnancy in the mothers who may have psychosocial and economic disadvantage because of their epilepsy. This could be achieved with an early intervention programme, as suggested by the authors.[1]


1.Arulmozhi T, Dhanaraj M, Rangaraj R, Vengatesan A. Physical growth and psychomotor development of infants exposed to antiepileptic drugs in utero. Neurol India 2006;54:42-7.  Back to cited text no. 1    
2.Perucca E. Birth defects after prenatal exposure to antiepileptic drugs. Lancet Neurol 2005;4:781-6.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Gaily E, Kantola-Sorsa E, Granstr φm ML. Intelligence in children of epileptic mothers. J Pediatr 1988;113:677-84.   Back to cited text no. 3    
4.Gaily E, Kantola-Sorsa E, Hiilesmaa V, Isoaho M, Matila R, Kotila M, et al. Normal intelligence in children with prenatal exposure to carbamazepine. Neurology 2004;62:28-32.   Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Adab N, Kini U, Vinten J, Ayres J, Baker G, Clayton-Smith J, et al. The longer term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatr 2004;75:1575-83.   Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Ali II, Schuh L, Barkley GL, Gates JR. Antiepileptic drugs and reduced bone mineral density. Epilep Behav 2004;5:296-300.  Back to cited text no. 6    

Copyright 2006 - Neurology India

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