18  Drugs

Anticonvulsive Drugs

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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Buehler BA, Delimont D, van Waes M, Finnell RH. Prenatal prediction of risk of the fetal hydantoin syndrome. N Engl J Med 1990; 322: 1567–72.

Ceci O, Loizzi P, Caruso G, Caradonna F, Clemente R, Ferreri R. Fetal malformations in an epileptic pregnant woman treated with carbamazepine. Zentralbl Gynäkol 1996; 118: 169–71.

Dean JC, Hailey H, Moore SJ, Lloyd DJ, Turnpenny PD, Little J. Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth. J Med Genet 2002; 39: 251–9.

Giardina S, Contarini A, Becca B. Maternal diseases and congenital malformations. Ann Ist Super Sanita 1993; 29: 69–76.

Holmes LB. Looking for long-term effects from prenatal exposures to anticonvulsants. Teratology 2001; 64: 175–6.

Janz D. Pregnancy and fetal development in epileptic women. Geburtshilfe Frauenheilkd 1984; 44: 428–34.

Koch S, Losche G, Jager R, et al. Major and minor birth malformations and antiepileptic drugs. Neurology 1992; 42: 83–8.

Kroes HY, Reefhuis J, Cornel MC. Is there an association between maternal carbamazepine use during pregnancy and eye malformations in the child? [review]. Epilepsia 2002; 43: 929–31.

Lowe SA. Drugs in pregnancy: anticonvulsants and drugs for neurological disease [review]. Best Pract Res Clin Obstet Gynaecol 2001; 15: 863–76.

McAuley JW, Anderson GD. Treatment of epilepsy in women of reproductive age: pharmacokinetic considerations [review]. Clin Pharmacokinet 2002; 41: 559–79.

Olafsson E, Hallgrimsson JT, Hauser WA, Ludvigsson P, Gudmundsson G. Pregnancies of women with epilepsy: a population-based study in Iceland. Epilepsia 1998; 39: 887–92.

Omtzigt JG, Los FJ, Grobbee DE, et al. The risk of spina bi-fida aperta after first-trimester exposure to valproate in a prenatal cohort. Neurology 1992; 42: 119–25.

Samrén EB, van Duijn CM, Koch S et al. Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy. Epilepsia 1997; 38: 981–90.

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Jan 11, 2016 | Posted by in FETAL MEDICINE | Comments Off on Drugs

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