Prothrombin and PIVKA-II levels in cord blood from newborn exposed to anticonvulsants during pregnancy

Abstract

Purpose: To determine whether anticonvulsant exposure during human pregnancy caused an increase of the abnormal form of prothrombin, known as PIVKA-II (prothrombin induced by vitamin K absence for factor II), and a decrease in total prothrombin, in the blood of the newborn. Methods: Cord blood was collected from the placenta at the time of parturition from 12 women who had received anticonvulsant therapy during pregnancy and from 11 control women. Results: PIVKA-II was present in cord blood from control mothers at low or nondetectable levels. In the same samples, total prothrombin concentrations were ~50% of adult levels, but there was wide variation between individuals. Exposure to carbamazepine (CBZ) alone during pregnancy was associated with markedly increased PIVKA-II levels in four of six samples and decreased total prothrombin levels for the whole group. High PIVKA-II levels also were recorded in one cord blood sample from a mother who received phenytoin (PHT) and vigabatrin (VGB). Two cases of PHT alone and one of valproic acid (VPA) alone were not associated with increased PIVKA-II levels. Conclusions: These results are consistent with the hypothesis that some anticonvulsants (particularly CBZ) interfere with vitamin K metabolism during pregnancy and may result in hematologic signs of vitamin K deficiency in the newborn.