Substances: Phenytoin, carbamazepine, valproic acid, phenobarbiturate.

Definition: Effects of anticonvulsive drugs with a known teratogenic effect on the fetus. In the presence of epilepsy, there is a two- to threefold increase in the risk of fetal anomalies, even without the effects of medication.

Incidence: The risk of fetal malformations lies at 10% if medications are given in early pregnancy. In patients with an autosomal-recessively inherited deficiency in epoxide hydrolase (a metabolic enzyme), the risk of fetal anomalies under the influence of anticonvulsive drugs is extremely high.

Associated malformations: Phenytoin and carbamazepine may cause facial dysmorphism, microcephaly, finger hypoplasia, nail hypoplasia, growth restriction, and mental impairment. Valproic acid and carbamazepine increase the risk of neural tube defects to 1%.

Clinical features: Central nervous system anomalies: microcephaly, holoprosencephaly, myelomeningocele. Facial anomalies: hypertelorism, cleft lip and palate, stubby nose, wide nasal bridge. Skeletal anomalies: hypoplasia of the distal phalanges, ulnar deviation of the thumb, hip dysplasia, short neck, pterygium of the neck, anomalies of the ribs and sternum. Cardiac malformations: VSD, pulmonary stenosis, aortic stenosis. Anomalies of the urogenital system: ambiguous genitalia, renal anomalies. Growth restriction and oligohydramnios.

Clinical management: Karyotyping (differential diagnosis). Measurement of epoxide hydrolase in amniotic fluid; this is still experimental. There is an increased risk of cranial bleeding if medications belonging to the hydantoin group are used. In this situation, vitamin K should be administered to the mother before the start of labor.

Procedure after birth: When the mother is receiving hydantoin, vitamin K should be given. Intracranial bleeding should be excluded. With carbamazepine, growth restriction and developmental disturbances are frequently expected at the neonatal stage.

Prognosis: Over 90% of women suffering from fits have normal children. The prognosis depends on the type and severity of fetal malformation.

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