Prof. Hideto Yamada, MD, PhD, Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan, Tel.: +81 78 382 6005, Fax: +81 78 382 6019, E-mail:
Thromb Haemost. 2015 Jul;114(1):65-9. doi: 10.1160/TH14-11-0928. Epub 2015 Apr 16.
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.
本研究旨在评估妊娠早期血浆蛋白 S(PS)活性、游离 PS、蛋白 C(PC)活性和凝血因子 XII(FXII)水平降低是否与不良妊娠结局相关。连续收集了 1220 名孕妇 8-14 孕周的外周血样本,检测血浆 PS 活性、游离 PS、PC 活性和 FXII 水平。定义截断值为<第 1 百分位数、<第 5 百分位数和<第 10 百分位数,这些值来自 933 名无并发症自然分娩孕妇的检测结果。PS 活性<第 10 百分位数与妊娠高血压(PIH)和重度 PIH 相关,游离 PS 水平<第 5 百分位数与子痫前期相关。FXII 水平<第 1 百分位数与<34 孕周早产(PD)相关,与<37 孕周 PD、胎儿生长受限或胎儿丢失均无关。多因素分析显示 PS 活性<第 10 百分位数(比值比 5.9,95%置信区间 1.7-18.1)和 BMI≥25 kg/m²(4.3,1.1-13.3)是重度 PIH 的独立危险因素。同样,游离 PS 水平<第 5 百分位数(4.4,1.0-14.3)和 BMI≥25 kg/m²(4.0,1.3-10.9)是子痫前期的独立危险因素。总之,妊娠早期 PS 活性和游离 PS 水平降低的孕妇可能有较高的 PIH、重度 PIH 或子痫前期风险。FXII 水平降低的孕妇可能有<34 孕周 PD 风险增加。