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Minor anomalies in offspring of epileptic mothers
E Gaily1, M L Granström, V Hiilesmaa
1I Department of Pediatrics, Helsinki University Hospital, Finland.
Insights
Epilepsy in mothers, not just antiepileptic drugs like phenytoin, is linked to minor physical anomalies in children. The risk of developmental issues from prenatal phenytoin exposure appears lower than previously thought.
Area of Science:
- Neurology
- Teratology
- Genetics
Background:
- Fetal hydantoin syndrome (FHS) is a condition associated with prenatal exposure to the antiepileptic drug phenytoin.
- Previous studies suggested a high risk of FHS and associated developmental disturbances.
Purpose of the Study:
- To investigate the association between maternal epilepsy, antiepileptic drug exposure, and minor physical anomalies in children.
- To re-evaluate the characteristics and prevalence of FHS.
Main Methods:
- A prospective study examined 121 children of mothers with epilepsy and 105 control children at age 5.5 years.
- Children were assessed for 80 minor physical anomalies, including features of FHS.
- Mothers and fathers were also examined for anomalies.
Main Results:
- Children of epileptic mothers showed a significant excess of anomalies characteristic of FHS compared to controls.
- Several anomalies previously linked to FHS were found to be genetically associated with epilepsy itself.
- Only hypertelorism and digital hypoplasia were specifically linked to phenytoin exposure.
- No phenytoin-exposed children exhibited all major FHS characteristics (acrofacial features, intellectual deficiency, growth retardation, microcephaly).
Conclusions:
- The concept of FHS may be inaccurate, with many "typical" features not caused by phenytoin but possibly by maternal epilepsy.
- The risk of developmental disturbances from intrauterine phenytoin exposure is likely lower than previously estimated.
Abstract:
In a prospective study, 121 children of mothers with epilepsy (study group) and 105 control children were examined in a blinded fashion at age 5 1/2 years for 80 minor physical anomalies, including nine typical features previously reported characteristic of fetal hydantoin syndrome. Of the study group, 106 children had been exposed to antiepileptic drugs (82 to phenytoin) during pregnancy; 44 (36%) mothers had had generalized convulsions during pregnancy. One hundred fourteen mothers and 87 fathers of study group children and 101 mothers and 58 fathers of control children were also examined. A significant excess of minor anomalies considered characteristic of hydantoin syndrome was observed in children of epileptic mothers and in epileptic mothers, compared with the control group. There was no excess of other minor anomalies studied. Several minor anomalies previously regarded as typical of fetal hydantoin syndrome were shown to be genetically linked to epilepsy. Only hypertelorism and digital hypoplasia were associated with phenytoin exposure. The current concept of the syndrome seems to be incorrect; most of the "typical" characteristics are not caused by phenytoin. None of the phenytoin-exposed children had all of the main characteristics of hydantoin syndrome (typical acrofacial features, intellectual deficiency, growth retardation, and microcephaly). The risk of developmental disturbance associated with intrauterine phenytoin exposure seems to be much lower than the 7% to 11% risk of fetal hydantoin syndrome reported earlier.