Merz E, Thode C, Alkier A, Eiben B, Hackelöer B J, Hansmann M, Huesgen G, Kozlowski P, Pruggmaier M, Wellek S
Department of Obstetrics and Gynecology. Hospital Nordwest, Frankfurt/Main, Germany.
Ultraschall Med. 2008 Dec;29(6):639-45. doi: 10.1055/s-2008-1027958. Epub 2008 Dec 15.
First-trimester screening at 11 - 14 weeks has been proven to be very useful in the early detection of chromosomal defects. The aim of this project was to develop a CE-certified new risk calculation program (PRC = Prenatal Risk Calculation) using a nationwide database.
The database underlying the new risk calculation procedure was established in Germany from 2003 through 2006. Overall, the database includes measurements from 70,030 pregnant women having given birth to healthy children. Following consideration of all pregnancies associated with a chromosomally abnormal outcome, the sample size was 451. The algorithm used for calculating the risk of a chromosomally abnormal outcome comprises the following variables: maternal age, crown-rump length (CRL) (restricted to a range from 45 - 84 mm or, equivalently, 11 + 1 - 14 + 0 weeks of gestation), nuchal translucency (NT), as well as the maternal serum parameters PAPP-A (pregnancy associated plasma protein A) and free beta-hCG (free human chorionic gonadotropin). In a preliminary cross-validation study, we applied both the new algorithm and the FMF UK program to an independent sample containing n = 40,568 pregnancies with negative outcome, n = 187 cases of trisomy 21, n = 34 trisomies 18 and n = 13 trisomies 13.
Using the primary sample of 70,030 pregnancies with a negative outcome, reference bands were constructed for the sonographic parameter fetal nuchal translucency and the biochemical parameters PAPP-A and free beta-HCG. Instead of MoM values we used "degree of extremeness" (DoE) values. This statistical parameter has been proven to give more precise results than the MoM measure because it assesses the deviation of the actual measurement value from the centre of the reference band expressed as a multiple of the width of the respective band section. The result of the risk calculation is visualized by means of a traffic light graph which allows the patient to comprehend her individual risk at first glance. The red color indicates a high risk, green a low risk, and yellow represents a moderate risk. In our preliminary cross-validation study the detection rate obtained for the German algorithm was 86.6 % for trisomy 21, 94.1 % for trisomy 18 and 92.4 for trisomy 13. The corresponding detection rates obtained with the same data by the FMF UK program were 86.1 %, 82.3 % and 69.2 % throughout. The false-positive rate was 5.0 % throughout.
The new risk calculation procedure of the FMF Germany (PRC) has been made available as a CE-certified computer program. In screening for trisomy 21 it yields results comparable to those of the program used by the FMF UK. Regarding the diagnosis of trisomy 13 and 18, even higher detection rates are currently achieved with the German algorithm. Program, data base and license key are available free of charge to registered members of the FMF Germany.
孕11至14周的孕早期筛查已被证明在染色体缺陷的早期检测中非常有用。本项目的目的是利用全国性数据库开发一个获得CE认证的新风险计算程序（PRC = 产前风险计算）。
新风险计算程序所依据的数据库于2003年至2006年在德国建立。总体而言，该数据库包含了70030名已生育健康儿童的孕妇的测量数据。在考虑了所有与染色体异常结局相关的妊娠后，样本量为451。用于计算染色体异常结局风险的算法包括以下变量：孕妇年龄、头臀长（CRL）（限制在45至84毫米范围内，或等效于妊娠11 + 1至14 + 0周）、颈部透明带（NT），以及孕妇血清参数妊娠相关血浆蛋白A（PAPP-A）和游离β-人绒毛膜促性腺激素（游离β-hCG）。在一项初步的交叉验证研究中，我们将新算法和英国胎儿医学基金会（FMF UK）程序应用于一个独立样本，该样本包含n = 40568例结局为阴性的妊娠、n = 187例21三体病例、n = 34例18三体病例和n = 13例13三体病例。
利用70030例结局为阴性的妊娠的原始样本，为超声参数胎儿颈部透明带以及生化参数PAPP-A和游离β-hCG构建了参考区间。我们使用“极端程度”（DoE）值而非中位数倍数（MoM）值。该统计参数已被证明比MoM测量能给出更精确的结果，因为它评估实际测量值与参考区间中心的偏差，以相应区间段宽度的倍数表示。风险计算结果通过交通信号灯图直观呈现，使患者能一眼了解其个体风险。红色表示高风险，绿色表示低风险，黄色表示中度风险。在我们的初步交叉验证研究中，德国算法对21三体的检测率为86.6%，对18三体为94.1%，对13三体为92.4%。英国胎儿医学基金会（FMF UK）程序使用相同数据得到的相应检测率分别为86.1%、82.3%和69.2%。总体假阳性率为5.0%。
德国胎儿医学基金会（FMF Germany）的新风险计算程序已作为获得CE认证的计算机程序提供。在21三体筛查中，其结果与英国胎儿医学基金会（FMF UK）使用的程序相当。关于13三体和18三体的诊断，目前德国算法能实现更高的检测率。该程序、数据库和许可证密钥可供德国胎儿医学基金会（FMF Germany）的注册成员免费使用。
