The probability of having a malformed child appears to be 2 to 3 times greater in epileptic women who receive diphenylhydantion early in pregnancy than in women who have no history of a convulsive disorder(1). We report an unusual cardiac malformation in a neonate born to a mother on phenytoin.

G, a 21-year-old primigravida was a known epileptic on anticonvulsant medication (phenytoin 100 mg twice a day) for 3 years prior to conception. She conceived spontaneously and was taking the drug all through her pregnancy. The pregnancy was otherwise uncomplicated and she delivered a male baby at 32 weeks of gestation after a prolonged rupture of membranes for 30 hours. The baby weighed 1600 g at birth and did not require resuscitation. Examination showed a preaxial polydactyly on the right hand, hypospadias, precordial activity and a grade III systolic murmur in the left parasternal area. The baby was pink and all pulses were well palpable. The systolic/diastolic pressure was 73/41 mm of Hg with a mean arterial pressure of 51 mm of Hg. He was started on tube feeds on day 1. Chest X ray on day 1 was unremarkable. The baby showed unusual weight gain and poor peripheral circulation on second day of life and progressed to cardiogenic shock on day 3. On day 3, chest radiograph showed increased vascularity and cardiomegaly. The shock progressed in spite of inotropic support and ventilation and the baby died on day 5 of life due to cardiogenic shock, and renal failure. Postmortem examination of the baby revealed type I truncus ateriosus, large ventricular septal defect, absent ductus arteriosus, large atrial septal defect and an absent right coronary artery(Fig. 1).

Fig. 1. Postmortem dissection of the heart with type I truncus arteriosus (arrow) and ventricular septal defect (VSD).

The features of fetal hydantoin syndrome include craniofacial anomalies, prenatal and postnatal growth deficiencies, mental retardation and limb defects. Less frequently observed abnormalities include microcephaly, ocular defects, cardiovascular anomalies, hypospadiasis, and umbilical and inguinal hernias(2).

Cardiac anomalies are the most life threatening, though cleft lip and cleft palate are the most common malformations(3). The incidence of congenital heart disease in an infant exposed to phenytoin in utero is four times greater than the infants not exposed to this medication. Ventricular septal defect is the most common cardiac anomaly and the other reported ones are patent ductus arteriosus, coarctation of aorta, pulmonary and aortic stenosis, pulmonary atresia, and tetralogy of Fallot(4). To the best of our knowledge truncus arteriosus with absent ductus and absent coronary artery has never been reported in association with phenytoin exposure in utero. The other anomalies i.e., ventricular septal defect, atrial septal defect, polydactly and hypospadiasis seen in the index child are well known manifestations of fetal hydantoin syndrome.

Should phenytoin be discontinued in pregnant epileptic women? The answer probably is "No" as almost every available antiepileptic drug has been associated with congenital malformation. Since the effects of the drug are dose dependent it is prudent to use them with regular drug monitoring and with downward adjustment of the dose when necessary(5). Supplementation with folic acid might also be considered.

1. Monson RR, Rosenberg L, Hartz CH, Shapiro S, Heinonen OP, Slone D. Diphenylhydantoin and selected congenital malformations. NEJM 1973; 289: 1049-1052.

2. Hill RM, Verniaud WM, Horning MG, McCulley LB, Morgan NF. Infants exposed in utero to antiepileptic drugs. Am J Dis Child 1974; 127: 645-653.

3. Speidel BD, Meadow SR. Maternal epilepsy and abnormalities of the fetus and newborn. Lancet 1972; 2: 839-843.

4. Swartjes JM, Van Geijn HP. Pregnancy and epilepsy. Eur J Obstet Gynecol Reprod Biol 1998; 76: 3-11.

5. Shillingford AJ, Weiner S. Maternal issues affecting the fetus. Clin Perinatol 2001; 28: 31-70.