Changes in amniotic fluid concentration of thrombin-antithrombin III complexes in patients with preterm labor: evidence of an increased thrombin generation.
OBJECTIVE
Preterm labor is associated with excessive maternal thrombin generation, as evidenced by increased circulating thrombin-antithrombin (TAT) III complexes concentration. In addition to its hemostatic functions, thrombin has uterotonic properties that may participate in the mechanism leading to preterm birth in cases of intrauterine bleeding. Thrombin also has a proinflammatory role, and inflammation is associated with increased thrombin generation. The aim of this study was to determine whether intra-amniotic infection/inflammation (IAI) is associated with increased amniotic fluid (AF) thrombin generation in women with preterm and term deliveries.


METHODS
This cross-sectional study included the following groups: (1) mid-trimester (n = 74); (2) term not in labor (n = 39); (3) term in labor (n = 25); (4) term in labor with IAI (n = 22); (5) spontaneous preterm labor (PTL) who delivered at term (n = 62); (6) PTL without IAI who delivered preterm (n = 59); (7) PTL with IAI (n = 71). The AF TAT III complexes concentration was measured by enzyme linked immunosorbent assay (ELISA). Non-parametric statistics were used for analysis.


RESULTS
(1) TAT III complexes were identified in all AF samples; (2) patients with PTL who delivered preterm, with and without IAI, had a higher median AF TAT III complexes concentration than those with an episode of PTL who delivered at term (p < 0.001, p = 0.03, respectively); (3) among patients with PTL without IAI, elevated AF TAT III complexes concentration were independently associated with a shorter amniocentesis-to-delivery interval (hazard ratio, 1.5; 95% CI, 1.07-2.1); (4) among patients at term, those with IAI had a higher median AF TAT III complexes concentration than those without IAI, whether in labor or not in labor (p = 0.02); (5) there was no significant difference between the median AF TAT III complexes concentration of patients at term with and without labor; (6) patients who had a mid-trimester amniocentesis had a lower median AF TAT III complexes concentration than that of patients at term not in labor (p < 0.001).


CONCLUSIONS
We present herein a distinct difference in the pattern of intra-amniotic thrombin generation between term and preterm parturition. PTL leading to preterm delivery is associated with an increased intra-amniotic thrombin generation regardless of the presence of IAI. In contrast, term delivery is associated with an increased intra-amniotic thrombin generation only in patients with IAI.
Erez
Offer
O
Perinatology Research Branch, NICHD, NIH, DHHS, Bethesda, Maryland, USA. prbchiefstaff@med.wayne.edu
Romer
Roberto
R
Vaisbuch
Edi
E
Chaiworapongsa
Tinnakorn
T
Kusanovic
Juan Pedro
JP
Mazaki-Tovi
Shali
S
Gotsch
Francesca
F
Gomez
Ricardo
R
Maymon
Eli
E
Pacora
Percy
P
Edwin
Samuel S
SS
Kim
Chong Jai
CJ
Than
Nandor Gabor
NG
Mittal
Pooja
P
Yeo
Lami
L
Dong
Zhong
Z
Yoon
Bo Hyun
BH
Hassan
Sonia S
SS
Mazor
Moshe
M
D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000378:metabolism*; D000990:Antithrombin III / Q000378:metabolism*; D002821:Chorioamnionitis / Q000378:metabolism; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007752:Obstetric Labor, Premature / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D012680:Sensitivity and Specificity; D047929:Term Birth / Q000378:metabolism
C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases