The Teratological Effects of Anticonvulsants and the Effects on Pregnancy and Birth

Abstract

The aim of this retrospective study is to clarify the medical and statistical evaluation of the effects of antiepileptic medication when given during pregnancy. (1) There was no statistically significant higher incidence of malformations in 199 children of treated mothers in comparison with 394 children of untreated mothers. However, the statistiscal hypothesis that there is no relationship could not be confirmed. We found a statistically significant relationship in cases of hare lip and cleft palate. But this relationship is open to question on medical grounds. Even if there were a relationship, the risk must be small, since probably hitherto unknown additional factors play a role. Therefore, anti-epileptic medication during pregnancy is not contraindicated. (2) Just because of the small incidence of anomalies in children, the number of investigated children of treated and untreated mothers has to be enlarged to almost 1,850 to assess if there is any risk at all. (3) Poor labour pains and poor drinking of the new-born may be due to sedative and spasmolytic side effects. These results have to be completed by a study in prospect. (4) It is worthwhile differentiating teratogenic and mutagenic effects, because anti-epileptic medication is generally started long before pregnancy begins. Evaluating teratological effects, the incidence and type of anomalies of the children of treated mothers, and of children of fathers treated for some time before conception have to be compared.

Multi‐institutional Study on the Teratogenicity and Fetal Toxicity of Antiepileptic Drugs: A Report of a Collaborative Study Group in Japan

“…The malformations most likely to occur are cleft lip a n d o r palate, congenital heart disease, and other dysmorphic abnormalities. To get reliable information on the teratogenic role of epilepsy itself, other kinds of research are being done: studies on the incidence of the malformed offspring whose fathers suffer from epilepsy (Meyer, 1973;Dansky, 1974;Shapiro et al, 1976;Annergers et al, 1978) and studies on the prevalence of relatives with epilepsy among the family of the patients with orofacial clefts likely to be found in the offspring of epileptic parents (Pashayan et a]., 1971; South, 1972;Erickson and Oakley, 1974;Saxen, 1975;Friis, 1979). However, it is not easy to establish a direct relationship between a specific antiepileptic agent and fetal malformation because etiology and the severity of epilepsy, as well as malformations of the mother herself, must all be taken into consideration.…”

Impact of early life exposure to antiepileptic drugs on neurobehavioral outcomes based on laboratory animal and clinical research

“…In addition, phenytoin exposure has been associated with decreased rate of body growth [27,29]. Despite early reports that showed a strong association between outcome and prenatal phenytoin exposure, a number of larger studies that were conducted more recently, in which phenytoin monotherapy was evaluated, did not find a significant association between phenytoin monotherapy and the symptoms previously identified as fetal hydantoin syndrome [30–32]. Nevertheless, concerns remain that phenytoin use in pregnancy could affect the fetus.…”

Teratogenicity of anticonvulsant drugs. I: Review of the literature

“…From Table I it is apparent that only three of these 16 studies are in fact case-control studies, as the other 13 compared the malformation rate observed with a general populational rate or made no comparison at all. The malformation rates among infants of epileptic mothers on anticonvulsants varied among the 16 series from 186 per 1, OOO (Meyer,[77]) to 19 per 1, OOO (Janz and Fuchs 1561). This variation would suggest that compiling all 16 studies to obtain a rate of 80.6 per 1, OOO is invalid.…”

“…A compilation of so-called case-control studies [5,7,10,26,39,49,51,56,70,77,85,103,[110][111][112]1211 is shown in Table I. The methods of ascertainment, the anomalies reported, and the collection of controls differ in many of the studies.…”