Activation of the Fibrinolytic Cascade Early in Pregnancy Among Women With Spontaneous Preterm Birth

OBJECTIVE: To evaluate the association of early pregnancy concentrations of thrombin-antithrombin III complex with subsequent spontaneous preterm birth. METHODS: In a nested case-control study, thrombin-antithrombin III complex was measured in plasma before 20 weeks of gestation (mean 9.9 weeks) among women without chronic conditions, preeclampsia, or growth restriction. C-reactive protein and non-high-density lipoprotein cholesterol were also measured. Women with spontaneous preterm birth before 34 weeks of gestation (n=29) and 34 weeks to 36 weeks of gestation (n=72) were compared with women with term births occurring at or after 37 weeks (n=219). Polychotomous logistic regression was used to relate elevated thrombin-antithrombin III complex (greater than 5.5 ng/mL), dyslipidemia (non-high-clensity lipoprotein cholesterol greater than the 90th percentile), and inflammation (C-reactive protein at or above 8 micrograms/mL) to risk of spontaneous preterm birth subtypes. RESULTS: Women with spontaneous preterm birth compared with term births had elevated thrombin-antithrombin III complex (P=.02), and they were more likely to have a thrombin-antithrom bin III complex greater than 5.5 ng/mL (P<.01). Women with thrombin-antithrombin III complex in the highest compared with lowest quartile had a 4.6-fold (95% confidence interval 1.3-15.8) increased risk for spontaneous preterm birth before 34 weeks of gestation, adjusted for body mass index, race, inflammation, dyslipidemia, and gestational age at sampling. There was a dose-response trend between thrombin-antithrombin III complex and spontaneous preterm birth before 34 weeks (P<.01) and 34 to 36 weeks (P=.03). CONCLUSION: There is evidence of early pregnancy systemic fibrinolysis among women with spontaneous preterm birth before 34 weeks of gestation independent of inflammation and dyslipidemia, perhaps secondary to microvascular injury.