Handbook of Genetic Counseling/Fetal Hydantoin Syndrome

Fetal Hydantoin Syndrome Etiology Prenatal hydantoin (dilantin, phenytoin) exposure History/Epidemiology Phenytoin= anticonvulsant first introduced in1938. Teratogenic effects were first recognized in 1964. Numerous studies have demonstrated increased risk for congenital defects, both major and minor. Study conducted from 1985-1992 332 newborns exposed to phenytoin (hydantoin, dilantin) during the 1st trimester A total of 15 (4.5%) had major birth defects, including: Cardiovascular Spina bifida Hypospadias Clinical Features Craniofacies: Broad nasal bridge, wide anterior fontanelle, low hairline, broad alveolar ridge, short neck, hypertelorism, microcephaly, cleft lip/palate, low set ears, epicanthal folds, ptosis, coloboma, coarse scalp hair. Limbs: Small or absent nails, hypoplasia of distal phalanges, altered palmar crease, digital thumb, dislocated hip Growth: Mild to moderate growth deficiency, usually prenatal in onset Performance: Occasional borderline to mild mental deficiency. Performance in childhood is usually better than that predicted in infancy Cardiovascular (occasional abnormalities): Aortic valvular stenosis, coarctation of aorta, PDA, septal defects GI (occasional abnormalities): Pyloric stenosis, duodenal atresia, anal atresia Other (occasional): Small nipples that are widely spaced, umbilical and inguinal hernia. Risks Risks of delivering a child with congenital defects is 2-3x greater for women taking dilantin than for the general population. Increased risk could be caused by epilepsy, the drugs, or a combination of the two. It is thought that the drugs are the causative factor. Risks of child having full syndrome is about 10% and the risk for having some of the effects of the disorder is an additional 33% Some reports have shown that phenytoin is a transplacental carcinogen. Tumors were reported to occur after in utero exposure to phenytoin in a few cases. Phenytoin may induce folic acid deficiency in the epileptic patient by impairing GI absorption or by increasing hepatic metabolism. Therefore, the risk for having a baby with a spinal abnormality is increased. Some risk of early hemorrhagic disease of the newborn. Occurs during the 1st 24 hours after birth and can be fatal. Exact mechanism: unknown. Drug is thought to deplete already low levels of fetal vitamin K therefore suppressing the vitamin K-dependent coagulation factors II, VII, IX, and X. Proposed treatment regimen: taking oral vitamin K during last 2 months of pregnancy, C section if difficult labor or trauma is suspected, administering intravenous vitamin K to the newborn in the delivery room (this regimen hasn't been tested in clinical controlled trials, but are logical). Risk of not taking phenytoin: pregnant patient can have seizures and can cause the baby to have fetal hypoxia. Breast Feeding Phenytoin is excreted into breast milk. Milk:plasma ratios range from 0.18 to 0.54. Little risk to the infant if maternal levels are kept in the therapeutic range Drowsiness and decreased sucking were observed in one infant, no other adverse effects have been reported. The American Academy of Pediatrics considers phenytoin to be compatible with breast feeding. References www.reprotox.org Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th edition. Baltimore: Williams & Wilkins. Jones KL. Smith's Recognizable Patterns of Human Malformations. 5th edition. W.B. Saunders Company: Philadelphia. 1997. Notes The information in this outline was last updated in 2002.