Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Hunan Jiahui Genetics Hospital, Changsha, China.
Genet Med. 2019 Sep;21(9):1998-2006. doi: 10.1038/s41436-019-0467-4. Epub 2019 Mar 4.
To assess the clinical performance of an expanded noninvasive prenatal screening (NIPS) test ("NIPS-Plus") for detection of both aneuploidy and genome-wide microdeletion/microduplication syndromes (MMS).
A total of 94,085 women with a singleton pregnancy were prospectively enrolled in the study. The cell-free plasma DNA was directly sequenced without intermediate amplification and fetal abnormalities identified using an improved copy-number variation (CNV) calling algorithm.
A total of 1128 pregnancies (1.2%) were scored positive for clinically significant fetal chromosome abnormalities. This comprised 965 aneuploidies (1.026%) and 163 (0.174%) MMS. From follow-up tests, the positive predictive values (PPVs) for T21, T18, T13, rare trisomies, and sex chromosome aneuploidies were calculated as 95%, 82%, 46%, 29%, and 47%, respectively. For known MMS (n = 32), PPVs were 93% (DiGeorge), 68% (22q11.22 microduplication), 75% (Prader-Willi/Angleman), and 50% (Cri du Chat). For the remaining genome-wide MMS (n = 88), combined PPVs were 32% (CNVs ≥10 Mb) and 19% (CNVs <10 Mb).
NIPS-Plus yielded high PPVs for common aneuploidies and DiGeorge syndrome, and moderate PPVs for other MMS. Our results present compelling evidence that NIPS-Plus can be used as a first-tier pregnancy screening method to improve detection rates of clinically significant fetal chromosome abnormalities.
评估一种扩展的非侵入性产前筛查（NIPS）测试（“NIPS-Plus”）在检测非整倍体和全基因组微缺失/微重复综合征（MMS）方面的临床性能。
共有 94085 名单胎妊娠的女性前瞻性入组研究。无中间扩增直接对游离血浆 DNA 进行测序，使用改进的拷贝数变异（CNV）调用算法确定胎儿异常。
共有 1128 例妊娠（1.2%）被评为具有临床意义的胎儿染色体异常阳性。这包括 965 例非整倍体（1.026%）和 163 例 MMS（0.174%）。从后续检测来看，T21、T18、T13、罕见三体和性染色体非整倍体的阳性预测值（PPV）分别为 95%、82%、46%、29%和 47%。对于已知的 MMS（n=32），PPV 为 93%（DiGeorge）、68%（22q11.22 微重复）、75%（Prader-Willi/Angelman）和 50%（Cri du Chat）。对于其余全基因组 MMS（n=88），联合 PPV 为 32%（CNV≥10 Mb）和 19%（CNV<10 Mb）。
NIPS-Plus 对常见非整倍体和 DiGeorge 综合征的阳性预测值较高，对其他 MMS 的阳性预测值适中。我们的研究结果有力地证明，NIPS-Plus 可作为一线妊娠筛查方法，提高临床显著胎儿染色体异常的检出率。
