Preterm labor leading to preterm delivery in the absence of inflammation/infection is associated with low maternal plasma protein Z concentrations


      Preterm parturition has been associated with excessive thrombin generation. Protein Z regulates factor Xa activity, thereby inhibiting the coagulation cascade. The objective of this study was to compare maternal plasma concentration of protein Z in patients presenting with preterm labor (PTL) and normal pregnancy.

      Study design

      A case control study was designed. Protein Z plasma concentration was measured in the following groups: 1) normal pregnant women (n=71); and 2) patients with PTL (<34 weeks). Women with PTL were classified into: a) PTL with intra-amniotic infection (IAI; n=35); b) PTL without IAI (n=54); and c) patients with PTL who delivered at term (n=49). Maternal plasma protein Z concentration was measured by sensitive immunoassay. Study groups were matched by gestational age and non-parametric analysis was performed.


      1) There was no correlation between maternal plasma protein Z concentration and gestational age in normal pregnancy; 2) Patients with PTL had a lower median plasma concentration of protein Z than patients with normal pregnancy (median 2.3 μl/ml, range 0.7-4.5 vs. median 2.4 μl/ml, range 1.1-3.4; p=0.013); 3) Women with PTL without IAI who delivered preterm had a lower median protein Z concentration than normal pregnancies (median 2.1 μl/ml, range 1.1-3.2 vs. median 2.4 μl/ml, range 1.1-3.4; p=0.003); 4) Of interest, PTL with IAI was not associated with lower plasma concentrations of protein Z, nor were those with PTL who delivered at term (p>0.05 for each).


      1) Patients with PTL have significantly lower plasma protein Z concentrations than normal pregnant women; and 2) A unique finding was that patients with PTL leading to preterm delivery in the absence of IAI had lower concentrations of protein Z than other patients with PTL. Collectively, these observations suggest that a subgroup of patients with PTL have a hemostatic disorder that implicates bleeding/thrombosis as a mechanism of disease.