Establishing trimester-specific reference intervals of vitamin K-dependent protein C, protein S, and antithrombin and exploring the impacts of abnormal anticoagulation tests on adverse perinatal complications or outcomes.

BACKGROUND

Owing to complex physiological changes that take place in the anticoagulation system during pregnancy, reference intervals (RIs) based on non-pregnant women are not optimal for clinical diagnosis and treatment. In this cohort study, we aimed to establish trimester-specific RIs of vitamin K-dependent protein C (PC), protein S (PS), and antithrombin (AT) in singleton pregnancies and assess the risks of developing adverse pregnancy outcomes.

METHODS

Using the nonparametric approach, the first- (n = 276), second- (n = 124), and third- (n = 182) trimester PC, PS, and AT testing results of healthy singleton pregnant women from January 2017 and December 2020 were included to establish the trimester-specific RIs. The retrospective associations between the anticoagulation tests of singleton pregnant women (n = 6,090) and pregnancy complications as well as perinatal outcomes were assessed by logistic regression analysis.

RESULTS

The trimester-specific RIs for the PS and AT showed decreasing trends over the entire pregnancy (p < 0.05), which was closely associated with metabolism and changes in demand of vitamin K. However, the level of PC was slightly increased from the first to the second trimester and dropped in the third trimester (p < 0.05). In the subsequent risk analysis, AT displayed negative associations between its plasma level and the odds of intrahepatic cholestasis of pregnancy, fetal growth restriction, and preterm birth.

CONCLUSION

With the established trimester-specific RIs of vitamin K-dependent PC, PS, and AT, our study sheds light on the potential application of these tests in identifying women with increased risks of developing various pregnancy complications and adverse postpartum outcomes.