Differences in the patterns of phenytoin-induced malformations following stiripentol coadministration in three inbred mouse strains

Finnell, Richard H.; Waes, Michael Van; Musselman, Andrea C.; Kerr, Brad; Levy, R H

doi:10.1016/0890-6238(93)90088-o

Cited by 13 publications

(4 citation statements)

References 22 publications

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“…Among specified CAs only oesophageal atresia/stenosis with or without tracheo-oesophageal fistula showed a higher risk after monotherapy (clomethiazol and ethosuximide), however, this association was based only on 2 cases. Previously the phenytoin and a possible higher risk of oesophageal atresia/stenosis was published in animal experiments [33] and a Swedish study showed a higher risk of anal atresia based on 4 cases but 2 also had oesophageal atresia [13].…”

Section: Discussionmentioning

confidence: 99%

Critical Evaluation of Antiepileptic Drugs in Epileptic Pregnant Women - Hungarian Experiences

Czeizel¹,

Bánhidy²

2011

Open Drug Saf J

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Abstract:The prevalence of epilepsy is 0.3-0.6% in pregnant women and the higher rate of structural birth defects, i.e. congenital abnormalities (CAs) was recognized in their children. There are four aims of this review based on the population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA), 1980-1996 with the good validity of CA-diagnoses. (I) Most studies on the teratogenic/fetotoxic effects of antiepileptic drugs (AED) had too small samples therefore underpowered, thus the evaluation the findings of different studies together are appropriate to draw significant conclusions, therefore the data of HCCSCA are presented here. Of 22,843 cases with CA, 95 (0.42%), while of 38,151 controls without CA, 90 (0.24 %) had mothers with medically recorded epilepsy (OR with 95% CI: 1.8, 1.3-2.4) and AED in the prenatal maternity logbook. (II) Hungary had different spectrum of AED as in Western countries, thus the teratogenic potential of some less-known AED (e.g. sultiame) can be evaluated. (III) The efficacy of recent special medical care of epileptic pregnant women introduced in 1990 is worth checking. There was no significant increase in the proportion of monotherapy but the rate of total CAs decreased by 20% in the 1990s compared to the 1980s. (IV) Folic acid may reduce the teratogenic potential of some AED, nevertheless this analysis revealed that folic acid was used less frequently by epileptic pregnant women than by non-epileptic pregnant women. Thus an international consensus statement is an urgent task in this topic.

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Section: Discussionmentioning

confidence: 99%

Critical Evaluation of Antiepileptic Drugs in Epileptic Pregnant Women - Hungarian Experiences

Czeizel¹,

Bánhidy²

2011

Open Drug Saf J

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“…This basic spectrum of birth defects was confirmed and expanded upon by subsequent investigations into the teratogenicity of PHT to include tracheoesophageal fistulas, cutaneous hemorrhages and NTDs. The differences in the observed pattern of malformations were generally attributable to the differences in species or strain of the experimental animals, route of administration and dosages used in the various studies [Finnell et al, 1993; Fritz et al, 1976; McDevitt et al, 1981; Paulson et al, 1979]. …”

Section: Antiepileptic Drugsmentioning

confidence: 99%

Antiepileptic drugs and pregnancy outcomes

Wlodarczyk

Palacios

George

et al. 2012

American J of Med Genetics Pt A

Self Cite

107

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The treatment of epilepsy in women of reproductive age remains a clinical challenge. While most women with epilepsy require anticonvulsant drugs for adequate control of their seizures, the teratogenicity associated with some antiepileptic drugs is a risk that needs to be carefully addressed. Antiepileptic medications are also used to treat an ever broadening range of medical conditions such as bipolar disorder, migraine prophylaxis, cancer and neuropathic pain. Despite the fact that the majority of pregnancies of women with epilepsy who are receiving pharmacological treatment are normal, studies have demonstrated that the risk of having a pregnancy complicated by a major congenital malformation is doubled when comparing the risk of untreated pregnancies. Furthermore, when antiepileptic drugs (AEDs) are used in polytherapy regimens, the risk is tripled, especially when valproic acid (VPA) is included. However, it should be noted that the risks are specific for each anticonvulsant drug. Some investigations have suggested that the risk of teratogenicity is increased in a dose-dependent manner. More recent studies have reported that in utero exposure to AEDs can have detrimental effects on the cognitive functions and language skills in later stages of life. In fact, the FDA just issued a safety announcement on the impact of VPA on cognition (Safety Announcement 6-30-2011). The purpose of this document is to review the most commonly used compounds in the treatment of women with epilepsy, and to provide information on the latest experimental and human epidemiological studies of the effects of antiepileptic drugs in the exposed embryos.

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“…This basic spectrum of birth defects was confirmed, and expanded upon, by subsequent investigations into the teratogenicity of PHT to include tracheoesophageal fistulas, cutaneous hemorrhages and NTDs. The differences in the pattern of malformations observed were generally attributable to the differences in species or strain of the experimental animals, route of administration and dosages used in the various studies [71,73,103,104]. …”

Section: Mechanisms Of Aed Teratogenicitymentioning

confidence: 99%

Teratogenic effects of antiepileptic drugs

Hill

Wlodarczyk

Palacios

et al. 2010

Expert Review of Neurotherapeutics

119

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Many antiepileptic drugs (AEDs) have therapeutic applications that extend beyond epilepsy to include neuropathic pain, migraine headaches and psychiatric disorders. The risk of some AEDs has been clearly established, but for newer drugs, small sample sizes and polytherapy exposures preclude a conclusive determination of their teratogenic potential. Most women with epilepsy will require AED therapy throughout their entire pregnancy to control seizures; the vast majority of pregnancies in women with epilepsy have positive outcomes. A conservative estimate suggests that AED monotherapy doubles, and polytherapy triples, the risk for major congenital malformations. Furthermore, while evidence is still accruing, recent investigations suggest that exposure to select AEDs results in altered cognitive function later in development. There is no evidence to suggest that additional folic acid supplementation ameliorates the increased risk of congenital malformations conferred by in utero AED exposure.

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Differences in the patterns of phenytoin-induced malformations following stiripentol coadministration in three inbred mouse strains

Cited by 13 publications

References 22 publications

Critical Evaluation of Antiepileptic Drugs in Epileptic Pregnant Women - Hungarian Experiences

Critical Evaluation of Antiepileptic Drugs in Epileptic Pregnant Women - Hungarian Experiences

Antiepileptic drugs and pregnancy outcomes

Teratogenic effects of antiepileptic drugs

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