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Major and minor birth malformations and antiepileptic drugs
S Koch1, G Lösche, E Jager-Romän
1Children's Hospital, Klinikum Rudolf Virchow, Free University, Berlin, Germany.
Insights
Children born to parents with epilepsy have a higher risk of malformations. Antiepileptic drug treatment during pregnancy may increase minor anomalies in infants, but this effect diminishes by age four.
Area of Science:
- Medical Genetics
- Developmental Pediatrics
- Neurology
Background:
- Epilepsy is a neurological disorder affecting a significant portion of the population.
- Genetic and environmental factors contribute to epilepsy development.
- The impact of parental epilepsy and its treatment on offspring congenital anomalies requires further investigation.
Purpose of the Study:
- To investigate the prevalence of malformations in infants of parents with epilepsy.
- To assess the influence of maternal versus paternal epilepsy on congenital anomalies.
- To evaluate the association between antiepileptic drug (AED) exposure during pregnancy and the occurrence of anomalies.
Main Methods:
- Comparative study design comparing infants of parents with epilepsy to a control group.
- Detailed assessment of major and minor anomalies in offspring.
- Analysis of specific AEDs (valproate, phenytoin, phenobarbital) and their teratogenic potential.
- Longitudinal follow-up of children at 1 and 4 years of age.
Main Results:
- Malformations were twice as prevalent in children of parents with epilepsy compared to controls.
- Maternal epilepsy was associated with a higher incidence of minor anomalies than paternal epilepsy.
- Increased minor anomalies were observed in infants exposed to AEDs in utero at 1 year, but this difference was not apparent at 4 years.
- Specific AEDs like valproate, phenytoin, and phenobarbital demonstrated teratogenic effects, with valproate being considerably teratogenic.
Conclusions:
- A shared genetic background may predispose individuals to both epilepsy and congenital anomalies.
- While AEDs can increase the risk of minor anomalies, the underlying genetic predisposition to epilepsy is a significant factor.
- Valproate, phenytoin, and phenobarbital exhibit specific teratogenic effects, necessitating careful consideration during pregnancy planning and management for women with epilepsy.
Abstract:
In a study of infants of parents with epilepsy, malformations were twice as prevalent in these children as in controls. Children of mothers with epilepsy had more minor anomalies than those of fathers with epilepsy or controls. At 1 year of age, a greater number of minor anomalies was seen in children of mothers with epilepsy who had received treatment with antiepileptic drugs (AEDs) during pregnancy, whereas at 4 years, no difference was observed. Type of epilepsy, seizures during pregnancy, plasma levels of phenytoin or phenobarbital in the medium range, and fetal intrauterine growth did not correlate with the number of minor anomalies. We suggest that the special genetic background that predisposes to epilepsy also renders the fetus more vulnerable to major and minor anomalies. Although linkage between epilepsy and malformation is stronger than between AEDs and malformations, valproate, phenytoin, and phenobarbital show specific teratogenic effects. In addition, all AEDs unspecifically increase the number of minor anomalies. Under therapeutic conditions, valproate may be regarded as considerably teratogenic and all other observed AEDs as weakly teratogenic.