Protein S and C4b-binding protein in fetal and neonatal blood

The levels of protein C, free protein S, C4b-binding protein and the distribution of total protein S between a free form and a conjugated form with C4b-binding protein, were measured in fetuses between 15 and 35 weeks of gestation, in newborns and in maternal blood throughout pregnancy. Fetal and newborn umbilical blood samples were obtained by cordocentesis; in the case of newborns, immediately after delivery. C4b-binding protein was detected in five out of seven newborns and in only three out of 20 fetuses. The fetuses (21, 24, 29 weeks, respectively) whose blood contained C4b-binding protein (10%, 29%, 12% of adult level, respectively), did not survive: the possible cause of death for one was given as viral infection; all three were severely deformed. Only free protein S was detected in fetal blood and the mean value was 40%. By contrast, the mean levels of protein C in the fetuses increased from 11% to 15.5% of adult levels with advancing gestation. We conclude that the relatively high levels of free protein S in fetal blood may contribute to its non-coagulability and compensate for the low protein C levels.