Low levels of plasma protein S, protein C and coagulation factor XII during early pregnancy and adverse pregnancy outcome

It was the study objective to evaluate whether low levels of plasma protein S (PS) activity, free PS, protein C (PC) activity and coagulation factor XII (FXII) during early pregnancy are related to adverse pregnancy outcomes. Peripheral blood samples were obtained at 8-14 gestational weeks (GW) from a consecutive series of 1,220 women. The levels of plasma PS activity, free PS, PC activity, and FXII were measured. Cut-off values were defined as < 1st, < 5th, and < 10th percentiles of values obtained from 933 women whose pregnancies ended in normal deliveries without complications. PS activity of < 10th percentile yielded risks of pregnancy-induced hypertension (PIH) and severe PIH, while free PS level of < 5th percentile yielded a risk of pre-eclampsia. FXII level of < 1st percentile yielded a risk of premature delivery (PD) at < 34 GW. None was associated with PD at < 37 GW, fetal growth restriction or fetal loss. A multivariate analysis demonstrated that PS activity of < 10th percentile (odds ratio 5.9, 95 % confidence interval 1.7-18.1) and body mass index (BMI) ≥ 25 kg/m² (4.3, 1.1-13.3) were independent risk factors for severe PIH. Similarly, free PS level of < 5th percentile (4.4, 1.0-14.3) and BMI ≥ 25 kg/m² (4.0, 1.3-10.9) were independent risk factors for pre-eclampsia. In conclusion, women with low levels of plasma PS activity and free PS during early pregnancy might have increased risks of PIH, severe PIH or pre-eclampsia. Women with low FXII level might have an increased risk of PD at < 34 GW.