早孕期 7～14 孕周唐氏综合征筛查（二联筛查）。

First-trimester combined screening for trisomy 21 at 7-14 weeks' gestation.

机构信息

School of Computing and Mathematics, University of Plymouth, Plymouth, UK.

出版信息

Ultrasound Obstet Gynecol. 2010 Oct;36(4):404-11. doi: 10.1002/uog.7755.

DOI:10.1002/uog.7755

PMID:20658511

Abstract

OBJECTIVE

To establish an algorithm for first-trimester combined screening for trisomy 21 with biochemical testing from 7 to 14 weeks' gestation and ultrasound testing at 11-13 weeks.

METHODS

This was a multicenter study of 886 pregnancies with trisomy 21 and 222 475 unaffected pregnancies with measurements of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 7-14 weeks' gestation. Multiple regression modeling of log-transformed marker values was used to produce log multiples of the median (MoM) values for PAPP-A and free β-hCG. The models included terms for the center attended and the machine used for biochemical analysis, gestational age, maternal racial origin, maternal weight, smoking status and method of conception. Bivariate Gaussian distributions were fitted to log MoM PAPP-A and log MoM free β-hCG in trisomy 21 and in unaffected pregnancies. In each case the patient-specific risk for trisomy 21 was estimated by multiplying the individual maternal age-related risk with the likelihood ratio (LR) for fetal nuchal translucency (NT) according to the mixture model and the combined LR for maternal serum free β-hCG and PAPP-A. Estimates of detection rates for trisomy 21 and false-positive rates were calculated for combined screening with measurements of NT at 12 weeks together with measurements of free β-hCG and PAPP-A from 8 to 13 weeks.

RESULTS

In trisomy 21 pregnancies the mean log MoM free β-hCG increased linearly with gestation between 7 and 14 weeks, whereas the relation between log MoM PAPP-A and gestation was fitted by a quadratic equation such that the maximum separation between trisomy 21 and unaffected pregnancies occurs at 9-10 weeks. At a false-positive rate of 3% the detection rate of combined screening at 12 weeks was 86% and this increased to 90% by biochemical testing at 9 weeks and ultrasound scanning at 12 weeks. The detection rate increased to 92% by measuring PAPP-A at 9 weeks and free β-hCG at the time of the scan at 12 weeks.

CONCLUSION

The performance of first-trimester biochemical screening for trisomy 21 is best at 9-10 weeks rather than at 7-8 or 11-14 weeks.

摘要

目的

建立一种适用于 7 至 14 孕周生化标志物检测联合 11 至 13 孕周超声检查的唐氏综合征（21 三体）的早孕期联合筛查算法。

方法

本研究为多中心研究，共纳入 886 例 21 三体及 222475 例 21 三体正常妊娠的病例，于 7 至 14 孕周检测游离β-人绒毛膜促性腺激素（β-hCG）和妊娠相关血浆蛋白 A（PAPP-A），采用多元回归分析对数转换后的标志物水平，建立 PAPP-A 和游离β-hCG 的中位数倍数（MoM）模型。该模型包含参加中心和生化分析仪器、孕周、孕妇种族、孕妇体重、吸烟状况和受孕方式等变量。对 21 三体和 21 三体正常妊娠分别拟合 PAPP-A 和游离β-hCG 的双变量高斯分布。根据混合模型和游离β-hCG 与 PAPP-A 的联合似然比（LR），将个体的母体年龄相关风险与患者特异性 21 三体风险相乘，计算每位患者的 21 三体风险。同时，将各孕周胎儿颈项透明层（NT）联合 8 至 13 孕周游离β-hCG 和 PAPP-A 测量值进行联合筛查，计算 21 三体的检出率和假阳性率。

结果

21 三体妊娠游离β-hCG 的 MoM 随孕周呈线性增加，从 7 周到 14 周；而 PAPP-A 的 MoM 与孕周的关系符合二次方程，21 三体与正常妊娠的最大分离发生在 9 至 10 孕周。假阳性率为 3%时，12 周联合筛查的检出率为 86%，9 周时增加到 90%（结合生化检查），12 周时增加到 92%（结合超声检查），9 周时单独测量 PAPP-A 和 12 周时联合测量 PAPP-A 和游离β-hCG 的检出率则为 92%。