Center for Fetal Medicine, Pregnancy and Ultrasound, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Acta Obstet Gynecol Scand. 2020 Jun;99(6):765-774. doi: 10.1111/aogs.13877. Epub 2020 May 12.
Currently fetal nuchal translucency (NT) ≥3.5 mm is an indication for invasive testing often followed by chromosomal microarray. The aim of this study was to assess the risks for chromosomal aberrations in fetuses with an NT 3.0-3.4 mm, to determine whether invasive prenatal testing would be relevant in these cases and to assess the residual risks in fetuses with normal non-invasive prenatal test (NIPT) results.
A retrospective study and meta-analysis of literature cases with NT between 3.0 and 3.4 mm and 2 cohorts of pregnant women referred for invasive testing and chromosomal microarray was performed: Rotterdam region (with a risk >1:200 and NT between 3.0 and 3.4 mm) tested in the period July 2012 to June 2019 and Central Denmark region (with a risk >1:300 and NT between 3.0 and 3.4 mm) tested between September 2015 and December 2018.
A total of 522 fetuses were referred for invasive testing and chromosomal microarray. Meta-analysis indicated that in 1:7.4 (13.5% [95% CI 8.2%-21.5%]) fetuses a chromosomal aberration was diagnosed. Of these aberrant cases, 47/68 (69%) involved trisomy 21, 18, and 13 and would potentially be detected by all NIPT approaches. The residual risk for missing a (sub)microscopic chromosome aberration depends on the NIPT approach and is highest if NIPT was performed only for common trisomies-1:21 (4.8% [95% CI 3.2%-7.3%]). However, it may be substantially lowered if a genome-wide 10-Mb resolution NIPT test was offered (~1:464).
Based on these data, we suggest that the NT cut-off for invasive testing could be 3.0 mm (instead of 3.5 mm) because of the high risk of 1:7.4 for a chromosomal aberration. If women were offered NIPT first, there would be a significant diagnostic delay because all abnormal NIPT results need to be confirmed by diagnostic testing. If the woman had already received a normal NIPT result, the residual risk of 1:21 to 1:464 for chromosome aberrations other than common trisomies, dependent on the NIPT approach, should be raised. If a pregnant woman declines invasive testing, but still wants a test with a broader coverage of clinically significant conditions then the genome-wide >10-Mb resolution NIPT test, which detects most aberrations, could be proposed.
目前，胎儿颈项透明层（NT）≥3.5mm 是进行有创性检测的指征，通常随后进行染色体微阵列分析。本研究的目的是评估 NT 在 3.0-3.4mm 之间的胎儿发生染色体异常的风险，以确定在这些情况下是否需要进行有创性产前检测，并评估无创产前检测（NIPT）结果正常的胎儿的剩余风险。
对 NT 在 3.0-3.4mm 之间的文献病例进行回顾性研究和荟萃分析，并对接受有创性检测和染色体微阵列的 2 组孕妇进行了队列研究：鹿特丹地区（风险>1:200 且 NT 在 3.0-3.4mm 之间）于 2012 年 7 月至 2019 年 6 月进行检测，丹麦中部地区（风险>1:300 且 NT 在 3.0-3.4mm 之间）于 2015 年 9 月至 2018 年 12 月进行检测。
共有 522 例胎儿被转介进行有创性检测和染色体微阵列分析。荟萃分析表明，13.5%（95%CI 8.2%-21.5%）的胎儿被诊断出染色体异常。在这些异常病例中，47/68（69%）涉及 21、18 和 13 三体，所有 NIPT 方法都有可能检测到。错过（亚）微染色体异常的剩余风险取决于 NIPT 方法，如果仅对常见三体-1:21 进行 NIPT（1:21（95%CI 3.2%-7.3%）），则风险最高。然而，如果提供全基因组分辨率为 10Mb 的 NIPT 测试，则该风险可能会大大降低（~1:464）。
基于这些数据，我们建议将 NT 的侵入性检测截止值设为 3.0mm（而不是 3.5mm），因为染色体异常的风险为 1:7.4。如果首先为女性提供 NIPT，则会出现明显的诊断延迟，因为所有异常的 NIPT 结果都需要通过诊断性检测来确认。如果女性已经接受了正常的 NIPT 结果，则取决于 NIPT 方法，其他非常见三体的染色体异常的剩余风险为 1:21 至 1:464，应予以提高。如果孕妇拒绝进行有创性检测，但仍希望进行具有更广泛临床意义的检测，则可建议进行全基因组>10Mb 分辨率的 NIPT 检测，该检测可检测到大多数异常。
