全基因组非侵入性产前检测在多胎妊娠中的表现和诊断价值。

Performance and Diagnostic Value of Genome-Wide Noninvasive Prenatal Testing in Multiple Gestations.

机构信息

Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, the Center for Human Genetics and the Department of Obstetrics and Gynecology, Universitair Ziekenhuis Leuven, Leuven, the Center for Medical Genetics, Universitair Ziekenhuis Gent, Ghent, the Center for Medical Genetics, Universitair Ziekenhuis Antwerpen, Antwerp, the Center for Medical Genetics, Universiteit Antwerpen, Antwerp, the Center for Medical Genetics, Centre Hospitalier Universitaire de Liège, Liège, the Center for Human Genetics, Université Libre de Bruxelles, Brussels, the Center for Human Genetics, Université Catholique de Louvain, Brussels, the Center for Medical Genetics, Institut de Pathologie et de Génétique Gosselies, Charleroi, the Center for Medical Genetics, Vrije Universiteit Brussel, Brussels, and the Department of Obstetrics, Women's Clinic, Universitair Ziekenhuis Gent, Ghent, Belgium.

出版信息

Obstet Gynecol. 2021 Jun 1;137(6):1102-1108. doi: 10.1097/AOG.0000000000004385.

DOI:10.1097/AOG.0000000000004385

PMID:33957658

Abstract

OBJECTIVE

To evaluate the accuracy and diagnostic value of genome-wide noninvasive prenatal testing (NIPT) for the detection of fetal aneuploidies in multiple gestations, with a focus on dichorionic-diamniotic twin pregnancies.

METHODS

We performed a retrospective cohort study including data from pregnant women with a twin or higher-order gestation who underwent genome-wide NIPT at one of the eight Belgian genetic centers between November 1, 2013, and March 1, 2020. Chorionicity and amnionicity were determined by ultrasonography. Follow-up invasive testing was carried out in the event of positive NIPT results. Sensitivity and specificity were calculated for the detection of trisomy 21, 18, and 13 in the dichorionic-diamniotic twin cohort.

RESULTS

Unique NIPT analyses were performed for 4,150 pregnant women with a multiple gestation and an additional 767 with vanishing gestations. The failure rate in multiple gestations excluding vanishing gestations ranged from 0% to 11.7% among the different genetic centers. Overall, the failure rate was 4.8%, which could be reduced to 1.2% after single resampling. There were no common fetal trisomies detected among the 86 monochorionic-monoamniotic and 25 triplet cases. Two monochorionic-diamniotic twins had an NIPT result indicative of a trisomy 21, which was confirmed in both fetuses. Among 2,716 dichorionic-diamniotic twin gestations, a sensitivity of 100% (95% CI 74.12-100%) and a specificity of 100% (95% CI 99.86-100%) was reached for trisomy 21 (n=12). For trisomy 18 (n=3), the respective values were 75% (95% CI 30.06-95.44%) sensitivity and 100% (95% CI 99.86-100%) specificity, and for trisomy 13 (n=2), 100% (95% CI 20.65-100%) sensitivity and 99.96% (95% CI 99.79-99.99%) specificity. In the vanishing gestation group, 28 NIPT results were positive for trisomy 21, 18, or 13, with only five confirmed trisomies.

CONCLUSION

Genome-wide NIPT performed accurately for detection of aneuploidy in dichorionic-diamniotic twin gestations.

摘要

目的

评估全基因组非侵入性产前检测（NIPT）在检测多胎妊娠胎儿非整倍体中的准确性和诊断价值，重点是双绒毛膜-双羊膜双胎妊娠。

方法

我们进行了一项回顾性队列研究，纳入了 2013 年 11 月 1 日至 2020 年 3 月 1 日期间在比利时 8 个遗传中心之一接受全基因组 NIPT 的多胎或多胎以上妊娠的孕妇数据。通过超声检查确定绒毛膜性和羊膜性。在 NIPT 结果阳性的情况下进行后续侵入性检测。

结果

对 4150 名多胎妊娠和 767 名消失妊娠的孕妇进行了独特的 NIPT 分析。不同遗传中心的多胎妊娠排除消失妊娠的失败率在 0%至 11.7%之间。总体而言，失败率为 4.8%，在单个重新采样后可降低至 1.2%。86 例单绒毛膜-单羊膜和 25 例三胎病例中均未发现常见的胎儿三体。2 例双绒毛膜-双羊膜双胎的 NIPT 结果提示 21 三体，在两个胎儿中均得到证实。在 2716 例双绒毛膜-双羊膜双胎妊娠中，21 三体的灵敏度为 100%（95%CI 74.12-100%），特异性为 100%（95%CI 99.86-100%）（n=12）。18 三体（n=3）的灵敏度分别为 75%（95%CI 30.06-95.44%）和 100%（95%CI 99.86-100%），13 三体（n=2）的灵敏度分别为 100%（95%CI 20.65-100%）和 99.96%（95%CI 99.79-99.99%）。在消失妊娠组中，28 例 NIPT 结果为 21、18 或 13 三体阳性，仅确认 5 例三体。