While the
warfarin embryopathy is well defined, central nervous system abnormalities associated with gestational
warfarin exposure require further definition. Based on the timing of
warfarin exposure in humans, it has been proposed that second- and third-trimester exposure predisposes to CNS abnormalities while first-trimester exposure more typically is associated with the
warfarin embryopathy. A case is presented of a liveborn male with
Dandy Walker malformation, agenesis of the corpus callosum, and Peter anomaly of the right eye who was exposed to
warfarin between the 8th and 12th weeks of gestation who had none of the stigmata of the
warfarin embryopathy. His is the first known case of exposure confined to the first trimester, and the fifth case of
Dandy Walker malformation among a total of 15 CNS cases associated with this
drug. This case offers evidence that
Dandy Walker malformation may represent a distinct complication of in utero first-trimester exposure, and consideration of these particular abnormalities with exposure limited to a period prior to the known appearance of
vitamin K-dependent
clotting factors suggests that
warfarin has a direct teratogenic effect on central nervous system morphogenesis.