Is thrombin activation predictive of subsequent preterm delivery?

OBJECTIVE: To determine the relation between thrombin generation (measured by thrombin-antithrombin [TAT] complexes) early in pregnancy and subsequent preterm delivery. STUDY DESIGN: Select cohort of 731 women undergoing indicated second trimester amniocentesis prospectively followed to delivery. Primary outcome was preterm delivery. TAT levels were examined continuously and categorized by quartiles. Multivariable techniques were applied to adjust for potential confounders. Receiver operating characteristic curve analysis was used to determine a discriminatory cutoff level for TAT complexes. RESULTS: TAT concentration was significantly higher in women who delivered preterm (median, 98.9 mcg/L) than in those who did not (median, 66.3 mcg/L; P < .001). This difference persisted when 55 spontaneous preterm deliveries (median, 87.6 mcg/L) and 34 indicated preterm deliveries (median, 117.7 mcg/L) were separately compared with controls (P = .04 and P < .001, respectively). Crude and adjusted odds ratio for preterm delivery in the upper 2 TAT quartiles relative to the uppermost quartile relative to the lowest quartile were 2.45 (95% confidence interval [CI], 1.36-4.72; P = .004) and 2.31 (95% CI, 1.18-4.65; P = .017), respectively. Despite these distinct differences, the area under the receiver operating characteristic curve was only 0.62 (95% CI, 0.56-0.69), indicating poor performance of TAT concentration as a risk discriminator. CONCLUSION: Amniotic fluid levels of TAT complexes in the second trimester are elevated in women who subsequently deliver preterm, suggesting that thrombin generation may be involved in the various etio-pathogenic mechanisms leading to preterm delivery.