In the TRIDENT-2 study, all pregnant women in the Netherlands are offered genome-wide non-invasive prenatal testing (GW-NIPT) with a choice of receiving either full screening or screening solely for common trisomies. Previous data showed that GW-NIPT can reliably detect common trisomies in the general obstetric population and that this test can also detect other chromosomal abnormalities (additional findings). However, evidence regarding the clinical impact of screening for additional findings is lacking. Therefore, we present follow-up results of the TRIDENT-2 study to determine this clinical impact based on the laboratory and perinatal outcomes of cases with additional findings. Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weight <2.3rd percentile (13.6% [24/177] vs 2.5% [3,892/155,491]; RR 5.5) were significantly increased compared to the general obstetric population. Of the 90 maternal findings, 12 (13.3%) were malignancies and 32 (35.6%) (mosaic) pathogenic copy number variants, mostly associated with mild or no clinical phenotypes. Data from this large cohort study provide crucial information for deciding if and how to implement GW-NIPT in screening programs. Additionally, these data can inform the challenging interpretation, counseling, and follow-up of additional findings.

在 TRIDENT-2 研究中，为荷兰的所有孕妇提供全基因组无创产前检测 (GW-NIPT)，可选择接受全面筛查或仅筛查常见三体性。先前的数据表明，GW-NIPT 可以可靠地检测普通产科人群中的常见三体性，并且该测试还可以检测其他染色体异常（其他发现）。然而，缺乏关于筛查额外发现的临床影响的证据。因此，我们提出 TRIDENT-2 研究的后续结果，以确定这种临床影响，基于实验室和围产期结果以及其他发现的病例。在 2017 年 4 月至 2019 年 4 月期间，在 402/110,739 次怀孕中发现了额外的发现（0.36%）。358 例病例的起源被证明是胎儿（n = 79；22.1%），（假设）限制性胎盘嵌合体（CPM）（n = 189；52.8%）或母体（n = 90；25.1%）。对于剩余的 44 个（10.9%），无法确定畸变的来源。大多数胎儿染色体畸变是致病性的并且与严重的临床表型相关（61/79；77.2%）。对于 CPM 病例，先兆子痫的发生率 (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5)，出生体重 <2.3% (13.6% [24/177] vs 2.5% [3,892] /155,491]；RR 5.5) 与一般产科人群相比显着增加。在 90 例母体发现中，12 例（13.3%）为恶性肿瘤，32 例（35.6%）（镶嵌）致病性拷贝数变异，主要与轻度或无临床表型相关。这项大型队列研究的数据为决定是否以及如何在筛查项目中实施 GW-NIPT 提供了关键信息。