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


METHODS
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.
Kusanovic
Juan Pedro
JP
Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, USA.
Espinoza
Jimmy
J
Romero
Roberto
R
Hoppensteadt
Debra
D
Nien
Jyh Kae
JK
Kim
Chong Jai
CJ
Erez
Offer
O
Soto
Eleazar
E
Fareed
Jawed
J
Edwin
Sam
S
Chaiwerapongsa
Tinnakorn
T
Than
Nador G
NG
Yoon
Bo Hyun
BH
Gomez
Ricardo
R
Papp
Zoltan
Z
Hassan
Sonia S
SS
D000293:Adolescent; D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry; D001798:Blood Proteins / Q000032:analysis* / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007752:Obstetric Labor, Premature / Q000097:blood*; D011247:Pregnancy; D014592:Uterine Hemorrhage / Q000097:blood*
D001798:Blood Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C026080:plasma protein Z