CONGENITAL SCHIZENCEPHALY ASSOCIATED WITH IN-UTERO WARFARIN EXPOSURE

The warfarin embryopathy is a well-defined complex of fetal anomalies generally accepted to result from first trimester exposure. Optic atro phy and dilation of the cerebral ventricles associated with blindness, microcephaly, and mental retardation have been reported following sec ond and third trimester exposure. In contrast to the consistent clinic al features observed in the warfarin embryopathy, the CNS effects seen in fetuses exposed in the later trimesters share little in terms of s pecific lesion or long-term clinical outcome. A case of schizencephaly in a coumadin-exposed fetus is presented. This report offers supporti ve evidence that the CNS sequellae of this agent are the result of vas cular accident and hemorrhage, not a direct effect on CNS morphogenesi s. The molecular basis for the adverse effects of warfarin derivatives on the fetus are reviewed. Warfarin derivatives exert both their embr yopathic and their fetopathic effects via pharmacologic action: inhibi tion of gamma carboxylation of osteocalcin and a similar carboxylation of the vitamin K dependent clotting factors. Therefore, we believe th at warfarin exposure in the second or third trimesters of pregnancy is equally dangerous to the fetus as that in the first. Heparin may be a superior alternative to warfarin for the prevention of thromboembolic disease in pregnant women with cardiac value prostheses.