Sources of Information

Over the years there have been many research papers published on this subject.  Below is an in depth list of all the journal papers that have been published since 1981

FACS Research papers from 1963 – 2013 

Time line:  Key publications which altered the way we think about anticonvulsant exposure.

 

1963 – Lawrence, A. Anti-epileptic drugs and the foetus. British Medical Journal 1973; 16; p267. Possibly the first report of problems in a child where an antiepileptic drug is considered the cause.

 

1970 – Meadow, R. Congenital abnormalities and anticonvulsant drugs. Proceedings of the Royal Society of Medicine 1970; 63: p12-13. The first group study into the incidence of major malformations.

 

1973 – Fedrick, J. Epilepsy and Pregnancy: a report from the Oxford record linkage study. British Medical Journal 1973; 2:p442-448. The first population based study.

 

1974 – Hill, R et al. Infants Exposed In Utero to Antiepileptic Drugs: A Prospective Study. The first prospective study to investigate this issue.

 

1974- Barr, M., et al. Digital hypoplasia and anticonvulsants during gestation: a teratogenic syndrome. The Journal of Pediatrics 1974; 84(2):p254-256. The authors suggest that a syndrome may be associated with prenatal exposure to phenytoin, phenobarbital and primidone exposure.

 

1975– Hanson, J.W. & Smith, D.W. The fetal hydantoin syndrome. The Journal of Pediatrics 1978; 307: p285-290. Termed the constellation of features noted in some children following exposure to phenytoin, phenobarbital and primidone as Fetal Hydantion Syndrome.

 

1976- Hanson, J.W., et al. Risks to the offspring of women treated with hydantoin anticonvulsants, with emphasis of the fetal hydantion syndrome. The Journal of Pediatrics 1976; 89(4): p662-668. The first paper to raise that a child’s intellectual abilities may be lower in children with fetal hydantion syndrome.

 

1980- Dalens, B. Teratogenicity of valproic acid. The Journal of Pediatrics 1980; 97(2):p332-333. The first report of an infant with major congenital malformations thought to be linked to exposure to sodium valproate.

 

1982 –Rovet, E. & Guibaud, P. Maternal valproic acid and congenital neural tube defects. The Lancet 1982; 2(8304): p937. – Demonstrates the potential association between prenatal exposure to VPA and spina bifida.

 

1988 –Ardinger, H., et al Verification of the Fetal Anticonvulsant Syndrome. American Journal of Medical Genetics 1988; 29:p171-185– the first group case series of children exposed prenatally to sodium valproate and highlights potential characteristics of the syndrome.

 

1996 – King, P.B., et al. Spina bifida and cleft lip among newborns of Norwegian Women. American Journal of Public Health 1996; 86(10):p1454-1457. Demonstrated that changes in anticonvulsant use across the country lead to an alteration in the type of birth defects seen in the children.

1997 – Samren, E.B.,  et al. Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy. Epilepsia 1997; 38(9): p981-990. This collaboration of a number of different research groups highlights the importance of the dose of the drug.

 

2000– Moore, S., et al. A clinical study of 57 children with fetal anticonvulsant syndromes. Journal of Medical Genetics 2000;37:p489-497. The first study into a group of children diagnosed with fetal anticonvulsant syndromes.

 

2001 –Adab, N., et al. The longer term outcome of children born to mothers with epilepsy. Journal of Neurology, Neurosurgery and Psychiatry 2004; 75:p1575-1583. The first study to include a large group of children exposed to sodium valproate and to find that they require increased levels of educational support.

 

2004– Gaily, E., et al. Normal intelligence in children with prenatal exposure to carbamazepine. Neurology 2004; 62:p28-32. This large and well designed study found that the IQ of children exposed to carbamazepine was not significantly different from a group of un-exposed children.

 

2006-Hunt, S., et al. Levetiracetam in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 2006; 67: p1876-1879. The first investigation into prenatal exposure to levetiracetam (Keppra) and birth defects.

 

2008 –Hunt, S., et al. Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 2008; 71: p272-276. The first paper to investigate prenatal exposure to topiramate.

 

2008 – Bromley, R., et al. Autism spectrum disorders following in utero exposure to antiepileptic drugs. Neurology 2008; 71: p1923-1924. The first prospective study to demonstrate an increased prevalence of autistic spectrum disorders in children exposed to sodium valproate.

 

2009– Meador, M., et al.  Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. The New England Journal of Medicine 2009; 360(16): p1597-1605. The largest prospective study into sodium valproate and lamotrigine demonstrating that the first is associated with reduced IQ.

 

2011 –Shallcross, R., et al. Child development following in utero exposure: levetiracetam vs sodium valproate. Neurology 76; p383-389. The first study to investigate the rate of developmental delay in a group of children exposed to levetiracetam.

 

2011– Tomson, T., et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurology 2011; 10: p609-617. The largest study to date which shows level of risk by dose of antiepileptic drug.

 

2013 – Bromley,R.L., et al. The Prevalance of Neurodevelopmental Disorders in Children Prenatally Exposed to Antiepileptic Drugs.  Journal of Neurology, Neurosurg, Psychiatry.  21013; 0: 1-7.

 

 

The information on this page is provided by Dr Rebecca Bromley, Clinical Psychologist and Researcher at the University of Liverpool.

 

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