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

Abstract

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.

Primary prevention of neural-tube defects and some other congenital abnormalities by folic acid and multivitamins: history, missed opportunity and tasks

“…Table 2 shows that the HCCSCA data confirmed the teratogenic potential of AEDs [Czeizel and Bánhidy, 2010], a higher risk of CL ± CP, cleft palate, cardiovascular CAs, hypospadias was been found, in agreement with the results of previous studies. Only the higher risk of oesophageal atresia/stenosis was unexpected but this finding was based on only three cases.…”

“…foetal hydantoin/dilantin/phenytoin and foetal valproate syndrome/effect), isolated CAs, and functional disturbances (e.g. mental retardation) in their children [Czeizel and Bánhidy, 2010]. The plasma level of AEDs needs to be controlled due to its decline during pregnancy: these examinations showed a decline in plasma folate level as well.…”

Maternal risk factors in the origin of isolated hypospadias: A population‐based case‐control study

“…This IHS inducing effect of valproate may be connected with its gonadotropin‐releasing hormone agonism. In general antiepileptic drugs induce characteristic CA‐syndromes such as fetal hydantoin or valproate syndrome/effect (Czeizel and Bánhidy ) but valproate may induce isolated CAs such as IHS as well.…”

Interpretation of Controversial Teratogenic Findings of Drugs Such As Phenobarbital

“…The teratogenic effect of anticonvulsant drugs was confirmed by several studies [4, 5]; however, different anticonvulsant drugs have different risks and spectrum of CAs [23]. Nevertheless, it had become an accepted view that epileptic pregnant women taking phenobarbital had a 2-3 times greater risk for delivering a child with CA over the general newborn population [4, 5].…”