Department of Obstetrics and Gynecology and Women's Health, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Am J Obstet Gynecol. 2022 Aug;227(2):259.e1-259.e14. doi: 10.1016/j.ajog.2022.01.019. Epub 2022 Jan 25.
Cell-free DNA noninvasive prenatal screening for trisomies 21, 18, and 13 has been rapidly adopted into clinical practice. However, previous studies are limited by a lack of follow-up genetic testing to confirm the outcomes and accurately assess test performance, particularly in women at a low risk for aneuploidy.
To measure and compare the performance of cell-free DNA screening for trisomies 21, 18, and 13 between women at a low and high risk for aneuploidy in a large, prospective cohort with genetic confirmation of results STUDY DESIGN: This was a multicenter prospective observational study at 21 centers in 6 countries. Women who had single-nucleotide-polymorphism-based cell-free DNA screening for trisomies 21, 18, and 13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. The test performance and test failure (no-call) rates were assessed for the cohort, and women with low and high previous risks for aneuploidy were compared. An updated cell-free DNA algorithm blinded to the pregnancy outcome was also assessed.
A total of 20,194 women were enrolled at a median gestational age of 12.6 weeks (interquartile range, 11.6-13.9). The genetic outcomes were confirmed in 17,851 cases (88.4%): 13,043 (73.1%) low-risk and 4808 (26.9%) high-risk cases for aneuploidy. Overall, 133 trisomies were diagnosed (100 trisomy 21; 18 trisomy 18; 15 trisomy 13). The cell-free DNA screen positive rate was lower in the low-risk vs the high-risk group (0.27% vs 2.2%; P<.0001). The sensitivity and specificity were similar between the groups. The positive predictive value for the low- and high-risk groups was 85.7% vs 97.5%; P=.058 for trisomy 21; 50.0% vs 81.3%; P=.283 for trisomy 18; and 62.5% vs 83.3; P=.58 for trisomy 13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. The trisomy rate was higher in the 287 cases with no-call results than patients with a result on a first draw (2.8% vs 0.7%; P=.001). The updated algorithm showed similar sensitivity and specificity to the study algorithm with a lower no-call rate.
In women at a low risk for aneuploidy, single-nucleotide-polymorphism-based cell-free DNA has high sensitivity and specificity, positive predictive value of 85.7% for trisomy 21 and 74.3% for the 3 common trisomies. Patients who receive a no-call result are at an increased risk of aneuploidy and require additional investigation.
游离胎儿 DNA 非侵入性产前筛查 21 三体、18 三体和 13 三体已迅速应用于临床实践。然而，以前的研究受到缺乏后续遗传检测的限制，无法确认结果并准确评估测试性能，尤其是在低三体风险的女性中。
在一个具有遗传结果确认的大型前瞻性队列中，测量和比较低风险和高风险的女性中游离胎儿 DNA 筛查 21 三体、18 三体和 13 三体的性能。
这是在 6 个国家的 21 个中心进行的一项多中心前瞻性观察性研究。对接受单核苷酸多态性游离胎儿 DNA 筛查 21 三体、18 三体和 13 三体的女性进行了前瞻性研究。从产前或新生儿 DNA 样本中获得遗传确认。评估了该队列的测试性能和测试失败（无结果）率，并比较了低和高先前三体风险的女性。还评估了一种针对妊娠结局进行盲法更新的游离胎儿 DNA 算法。
共纳入 20194 名中位妊娠 12.6 周（四分位距，11.6-13.9）的女性。在 17851 例（88.4%）中获得了遗传结果：13043 例（73.1%）低风险和 4808 例（26.9%）高风险的非整倍体病例。总的来说，诊断出 133 例三体（100 例 21 三体；18 例 18 三体；15 例 13 三体）。低风险组与高风险组的游离胎儿 DNA 筛查阳性率较低（0.27%比 2.2%；P<.0001）。两组的灵敏度和特异性相似。低风险组和高风险组的阳性预测值分别为 85.7%和 97.5%；21 三体，P=.058；50.0%和 81.3%；18 三体，P=.283；62.5%和 83.3%；13 三体，P=.58。总体而言，602 例（3.4%）患者在第一次抽取后无结果，287 例（1.61%）在包括第二次抽取后无结果。无结果的 287 例患者的三体发生率高于第一次抽取有结果的患者（2.8%比 0.7%；P=.001）。更新后的算法与研究算法具有相似的灵敏度和特异性，无结果率较低。
在低三体风险的女性中，基于单核苷酸多态性的游离胎儿 DNA 具有较高的灵敏度和特异性，21 三体的阳性预测值为 85.7%，3 种常见三体的阳性预测值为 74.3%。获得无结果的患者发生三体的风险增加，需要进一步检查。
