早孕期联合检测胎盘生长因子、游离β-人绒毛膜促性腺激素和妊娠相关血浆蛋白-A 对 21 三体综合征的筛查

First-trimester combined screening for trisomy 21 with different combinations of placental growth factor, free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A.

机构信息

Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany.

出版信息

Ultrasound Obstet Gynecol. 2012 Nov;40(5):530-5. doi: 10.1002/uog.11173.

DOI:10.1002/uog.11173

PMID:22611005

Abstract

OBJECTIVE

To examine placental growth factor (PlGF) in euploid and trisomy 21 pregnancies at 11-13 weeks' gestation and to model the impact on first-trimester combined screening.

METHODS

PlGF was measured in 509 (409 euploid and 100 trisomic) fetal serum samples derived from prospective first-trimester combined screening for trisomy 21 at 11-13 weeks' gestation. The serum samples were stored at -80°C, following the measurement of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels, for median time spans of 0.9 and 4.1 years in the euploid and trisomy 21 pregnancies, respectively. The effect of additional PlGF measurement at the time of combined screening was investigated by simulating fetal nuchal translucency (NT) measurements and multiples of the median (MoM) values for PAPP-A, free β-hCG and PlGF for 20,000 euploid and 20,000 trisomy 21 pregnancies. Patient-specific combined risks were calculated based on maternal age and fetal NT in addition to free β-hCG, PAPP-A and PlGF, PAPP-A and PlGF or free β-hCG and PlGF, and detection and false-positive rates were calculated.

RESULTS

Median PlGF-MoM was 1.0 (95% confidence interval (CI), 0.96-1.04) in euploid fetuses and significantly lower, at 0.73 (95% CI, 0.70-0.76), in trisomy-21 fetuses (P < 0.0001). There was no significant dependency between PlGF-MoM and either gestational age at the time of blood sampling (r = 0.087, P = 0.392) or sample storage time (r = 0.028, P = 0.785). Modeled detection and false-positive rates for first-trimester combined screening (based on maternal and gestational age, fetal NT and maternal serum biochemistry) without PlGF were 85% and 2.7% for a fixed risk cut-off of 1:100. The addition of PlGF increased the detection rate to 87% and reduced the false-positive rate to 2.6%. Screening by maternal age and fetal NT in combination with PlGF and PAPP-A or in combination with PlGF and free β-hCG provided detection rates of 82% and 79%, with false-positive rates of 2.7% and 3.0%, respectively.

CONCLUSION

In pregnancies with trisomy 21 PlGF is reduced. The impact on the overall screening performance for trisomy 21 is low and does not justify the measurement of PlGF solely for trisomy 21 screening. However, as PlGF is measured with the aim of assessing the risk for pre-eclampsia, further improvement in screening for trisomy 21 can be considered as an added benefit.

摘要

目的

研究 11-13 孕周正常二倍体和 21 三体胎儿胎盘生长因子（PlGF），并建立模型以分析其对早孕期二联筛查的影响。

方法

前瞻性收集 509 例（409 例二倍体，100 例 21 三体）11-13 孕周接受早孕期二联筛查的孕妇血清，检测游离β-人绒毛膜促性腺激素（β-hCG）和妊娠相关血浆蛋白-A（PAPP-A）水平，并于-80°C 储存血清。二倍体和 21 三体组分别随访中位数 0.9 年和 4.1 年。通过模拟胎儿颈项透明层（NT）测量值和中位数倍数（MoM）值，以及 20000 例二倍体和 20000 例 21 三体妊娠的 PAPP-A、游离β-hCG 和 PlGF 倍数，研究联合筛查时额外检测 PlGF 对检测率的影响。基于母体年龄和胎儿 NT 以及游离β-hCG、PAPP-A 和 PlGF、PAPP-A 和 PlGF 或游离β-hCG 和 PlGF，计算患者特定的联合风险，并计算检测率和假阳性率。

结果

二倍体胎儿 PlGF-MoM 中位数为 1.0（95%置信区间（CI）：0.96-1.04），21 三体胎儿显著降低，为 0.73（95%CI：0.70-0.76）（P<0.0001）。PlGF-MoM 与采血时的孕周（r=0.087，P=0.392）或样本储存时间（r=0.028，P=0.785）无显著相关性。未加入 PlGF 时，基于母体年龄和孕周、胎儿 NT 和母体血清生化指标的早孕期二联筛查的检测率和假阳性率分别为 85%和 2.7%，固定风险截断值为 1:100。加入 PlGF 后，检测率提高至 87%，假阳性率降低至 2.6%。仅以母体年龄和胎儿 NT 为基础，结合 PlGF 和 PAPP-A 或 PlGF 和游离β-hCG 进行筛查，检测率分别为 82%和 79%，假阳性率分别为 2.7%和 3.0%。