Plasma protein Z concentrations in pregnant women with idiopathic intrauterine bleeding and in women with spontaneous preterm labor

Abstract

OBJECTIVES: Preterm parturition has been associated with decidual vascular disorders and excessive thrombin generation. The objective of this study was to examine maternal plasma concentrations of protein Z in normal pregnancies, as well as in those presenting with spontaneous preterm labor (PTL) and intrauterine bleeding during pregnancy. STUDY DESIGN: A cross-sectional study was designed to include patients with preterm labor and intact membranes and those with idiopathic intrauterine bleeding during pregnancy. Protein Z plasma concentrations were measured in the following groups: (1) normal pregnant women (n = 71); (2) patients at term with (n = 67) and without labor (n = 88); (3) patients with spontaneous PTL before 34 weeks who were classified into: (a) PTL with intra-amniotic infection/inflammation (IAI; n = 35), (b) PTL without IAI (n = 54), and (c) patients with PTL who delivered at term (n = 49); and (4) patients with idiopathic intrauterine bleeding in the second and third trimester who were divided into: (a) subsequent spontaneous PTL and delivery, and (b) term delivery. Maternal plasma protein Z concentration was measured by a specific and sensitive immunoassay. Moreover, the amniotic fluid concentration of protein Z was determined in a subset of patients with preterm labor (n = 30). RESULTS: (1) There was no correlation between maternal plasma protein Z concentration and gestational age in normal pregnant women. (2) The mean maternal plasma concentration of protein Z was significantly lower in women during spontaneous labor at term than in those not in labor (mean 2.15 microg/mL (95% CI 2.01-2.29) vs. mean 2.45+/-0.52 microg/mL (95% CI 2.34-2.56), respectively; p = 0.001). (3) Women with PTL without IAI who delivered preterm had a significantly lower mean protein Z concentration than normal pregnant women (mean 2.12 mug/mL (95% CI 1.98-2.26) vs. mean 2.39 microg/mL (95% CI 2.28-2.5); p = 0.008). (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). (5) No differences were found in the maternal plasma concentrations of anti-protein Z antibodies between normal pregnancies and those with spontaneous PTL. (6) Patients with idiopathic intrauterine bleeding who had spontaneous PTL and delivery had a significantly lower mean plasma protein Z concentration than those who delivered at term (mean 1.24 microg/mL (95% CI 1.08-1.4) vs. mean 1.49+/-0.47 microg/mL (95% CI 1.33-1.65), respectively; p = 0.03). (7) Amniotic fluid was found to contain immunoreactive protein Z. CONCLUSIONS: (1) Patients with PTL leading to preterm delivery in the absence of IAI had a significantly lower plasma concentration of protein Z than those with normal pregnancies. (2) Patients with idiopathic intrauterine bleeding and subsequently spontaneous PTL and delivery had a significantly lower plasma concentration of protein Z than those with idiopathic intrauterine bleeding who delivered at term. (3) Protein Z was present in the amniotic fluid of patients with PTL. Collectively, these observations suggest that a subgroup of patients with PTL have a hemostatic disorder that involves bleeding/thrombosis as a mechanism of disease.