Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort.
Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort.
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DOI：
10.1097/aog.0000000000000363
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发表时间：
2014-08
影响因子：
7.2
通讯作者：
Rabinowitz M
中科院分区：
文献类型：
--
作者：
Pergament E;Cuckle H;Zimmermann B;Banjevic M;Sigurjonsson S;Ryan A;Hall MP;Dodd M;Lacroute P;Stosic M;Chopra N;Hunkapiller N;Prosen DE;McAdoo S;Demko Z;Siddiqui A;Hill M;Rabinowitz M
评估基于单核苷酸多态性的非侵入性产前筛查高危和低危人群单次静脉穿刺术中胎儿非整倍体的效果。共收集妊娠7周及以上孕妇血标本1,064份，符合规范1,051份，低危518份(49.3%)。对无细胞DNA进行扩增、测序，并使用SNPs算法进行下一代非整倍体检测。样本被称为21，18，13三体，或单体X，或整倍体，男性或女性。966个样本(91.9%)成功地产生了无细胞DNA结果。其中，21三体(58/58，CI：93.8~100%)、13三体(12/12，CI：73.5~100%)、胎儿性别(358/358女性，CI：99.0~100%；418/418男性，CI：99.1~100%)、18三体(24/25，CI：79.7~99.9%)、X单体(9/10，CI：55.5~99.8%)的敏感性为100%。21和13三体的特异度分别为905/905[CI：99.6~100%]和953/953[CI：99.6~100%]；18三体和X单体的特异度为99.9%(938/939[CI：99.4~100%]和953/954[CI：99.4~100%])。然而，16%(20/125)的非整倍体样本没有返回结果；50%(10/20)的胎儿部分低于整倍体妊娠的1.5个百分位数。非整倍体率明显高于对照组(P<；0.001，优势比：9.2，CI：4.4~19.0)。在低危人群和高危人群中，敏感性和特异性没有差别。这种无创性产前筛查在高危和低危人群中具有很高的敏感性和特异性。非整倍体样本明显更有可能不返回结果；非整倍体样本的数量在低胎儿比例的样本中尤其增加。这突显了重抽的重要性，或者在极少数情况下，基于低胎儿比例的侵入性手术。
To estimate performance of a single-nucleotide-polymorphism–based noninvasive prenatal screen for fetal aneuploidy in high-risk and low-risk populations upon single venopuncture. One thousand sixty-four maternal blood samples from 7 weeks of gestation and beyond were included; one thousand fifty-one were within specifications, 518 (49.3%) low-risk. Cell-free DNA was amplified, sequenced, and analyzed using the Next-generation Aneuploidy Test Using SNPs algorithm. Samples were called as trisomies 21, 18, 13, or monosomy X, or euploid, and male or female. Nine hundred sixty-six samples (91.9%) successfully generated a cell-free DNA result. Among these, sensitivity was 100% for trisomy 21 (58/58, CI: 93.8–100%), trisomy 13 (12/12, CI: 73.5–100%), and fetal sex (358/358 female, CI:99.0–100%; 418/418 male, CI: 99.1–100%), 96.0% for trisomy 18 (24/25, CI: 79.7–99.9%), and 90% for monosomy X (9/10, CI: 55.5–99.8%). Specificity for trisomies 21 and 13 was 100% (905/905 [CI: 99.6–100%] and 953/953 [CI: 99.6–100%], respectively) and for trisomy 18 and monosomy X was 99.9% (938/939 [CI: 99.4–100%] and 953/954 [CI: 99.4–100%], respectively). However, 16% (20/125) of aneuploid samples did not return a result; 50% (10/20) had a fetal fraction below the 1.5th percentile of euploid pregnancies. Aneuploidy rate was significantly higher in these samples (p<0.001, odds ratio: 9.2, CI: 4.4–19.0). Sensitivity and specificity did not differ in low-risk and high-risk populations. This noninvasive prenatal screen performed with high sensitivity and specificity in high-risk and low-risk cohorts. Aneuploid samples were significantly more likely to not return a result; the number of aneuploidy samples was especially increased among samples with low fetal fraction. This underscores the importance of redraws or, in rare cases, invasive procedures based on low fetal fraction.