Prothrombin and PIVKA-II levels in cord blood from newborn exposed to anticonvulsants during pregnancy.
OBJECTIVE
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 approximately 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.
Howe
A M
AM
Department of Anatomy, University of Sydney, NSW, Australia.
Oakes
D J
DJ
Woodman
P D
PD
Webster
W S
WS
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011498:Protein Precursors / Q000032:analysis*; D011516:Prothrombin / Q000032:analysis*; D014812:Vitamin K / Q000097:blood; D014813:Vitamin K Deficiency / Q000097:blood
D000927:Anticonvulsants; D015415:Biomarkers; D014408:Biomarkers, Tumor; D011498:Protein Precursors; D014812:Vitamin K; C008208:acarboxyprothrombin; D011516:Prothrombin