目的:评估两种类型的无创性产前筛查(NIPS)扩张对无主要结构异常的妊娠的理论附加值,与常用的5-NIPS(即,NIPS针对染色体13、18、21、X和Y),和染色体微阵列分析(CMA)。
方法:这项回顾性队列研究是基于所有正常超声妊娠的CMA结果(包括具有软标记和孕妇血清筛查异常的妊娠)。我们已经计算了5-NIPS的理论产率,扩展NIPS对常见微缺失的附加价值(1p36.3-1p36.2、4p16.3-4p16.2、5p15.3-5p15.1、15q11.2-15q13.1和22q11.2),以及全基因组NIPS可检测的发现(包括>5Mb的变异),并通过侵入性试验的指征将其与整个队列和亚组的CMA产量进行比较。
结果:在检查的8,605例怀孕中,证实了122(1.4%)临床上显著的CMA结果。其中,44(36.1%)理论上可检测到5-NIPS,在642例孕妇血清筛查异常的孕妇中,占1.56%,318例有软标记的妊娠中0.63%,在4,378名高龄(35岁以上)妇女中,0.62%,35岁以下女性的比例为0.15%。在整个队列中检测到3例常见的微缺失(0.03%),以及9个全基因组NIPS可检测结果(0.1%)。与CMA相比,扩展的NIPS的附加值明显较低,对于整个队列和亚组。
结论:5-NIPS,甚至全基因组NIPS将错过63.9%和54.1%的临床显著CMA发现,分别。NIPS的附加值扩展到包括常见的微缺失,与5-NIPS相比,约为0.03%,针对大型CNV的全基因组NIPS的总价值约为0.1%,与CMA的附加值相比,两者都要低得多。这些结果对保健医生来说很重要,促进夫妇就产前遗传筛查和检测做出明智的决定。本文受版权保护。保留所有权利。
To evaluate the theoretical added value of two types of non-invasive prenatal screening (NIPS) expansions in pregnancies without major structural anomalies over the commonly used NIPS for chromosomes 13, 18, 21, X and Y (5-NIPS) and to compare them with the added value of chromosomal microarray analysis (CMA).
This was a retrospective cohort study based on CMA results of all pregnancies with normal ultrasound (including pregnancies with soft markers and with abnormal maternal serum screening) that had undergone amniocentesis between January 2013 to February 2022 and were registered in the database of the Rabin Medical Center genetic laboratory. We calculated the theoretical yield of 5-NIPS and compared the added value of expanded 5-NIPS for common microdeletions (1p36.3-1p36.2, 4p16.3-4p16.2, 5p15.3-5p15.1, 15q11.2-15q13.1 and 22q11.2) and genome-wide NIPS (including variants > 5 Mb) with the added value of CMA in the overall cohort and in subgroups according to indication for invasive testing.
Among the 8605 examined pregnancies, 122 (1.4%) clinically significant CMA results were demonstrated. Of these, 44 (36.1%) were theoretically detectable on 5-NIPS, with the rates of 1.56% in 642 pregnancies with abnormal maternal serum screening, 0.63% in 318 pregnancies with soft markers, 0.62% in 4378 women with advanced maternal age (≥ 35 years) and 0.15% in 3267 women younger than 35 years. In addition to aneuploidies detectable on 5-NIPS, three (0.03%) cases detectable on 5-NIPS expanded for common microdeletions and nine (0.10%) cases detectable on genome-wide NIPS (excluding common microdeletions) were identified in the overall cohort. The added value of expanded NIPS tools over 5-NIPS was significantly lower compared with that of CMA, for the overall cohort and subgroups.
5-NIPS and even genome-wide NIPS would miss 63.9% and 54.1% of clinically significant CMA findings, respectively. The added value of 5-NIPS expanded to detect common microdeletions over 5-NIPS is about 0.035%, and the overall added value of genome-wide NIPS aimed at large CNVs is about 0.14%, both much lower compared with the added value of CMA (0.91%). These findings should assist healthcare practitioners in guiding couples towards informed decision-making regarding the choice between prenatal invasive testing and NIPS. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.