Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
Ultrasound Obstet Gynecol. 2013 Jan;41(1):21-5. doi: 10.1002/uog.12299. Epub 2012 Nov 23.
To assess the performance of chromosome-selective sequencing of maternal plasma cell-free DNA (cfDNA) in non-invasive prenatal testing for trisomy 13.
Two-phase case-control study on a single plasma sample per case. The first phase was used to optimize the trisomy 13 algorithm, which was then applied to a second dataset to determine the risk score for trisomy 13 by laboratory personnel who were blinded to the fetal karyotype.
In the first phase, trisomy 13 risk scores were given for 11 cases of trisomy 13 and 145 euploid cases at 11-13 weeks' gestation. The test identified seven (63.6%) cases of trisomy 13 with no false positives. The trisomy 13 algorithm was subsequently modified and the trisomy 13 risk score was > 99% in all 11 cases of trisomy 13 and < 0.01% in all 145 euploid cases. In the second phase, the new algorithm was used to generate trisomy 13 risk scores for 10 cases of trisomy 13 and 1939 euploid cases. The trisomy 13 risk scores were > 99% in eight (80.0% (95% confidence interval (CI), 49.0-94.3%)) cases of trisomy 13. In the 1939 euploid cases the risk score for trisomy 13 was < 0.01% in 1937 (99.9%), 0.79% in one, and > 99% in one. Therefore, at the predefined risk cut-off of 1% for classifying a sample as high or low risk, the false-positive rate (FPR) was 0.05% (95% CI, 0.0-0.3%).
Chromosome-selective sequencing of cfDNA can detect the majority of cases of trisomy 13 at an FPR of less than 0.1%.
评估母体外周血游离 DNA（cfDNA）染色体选择性测序在非侵入性产前筛查 13 三体中的性能。
对每个病例采用单一样本的两阶段病例对照研究。第一阶段用于优化 13 三体算法，然后由对胎儿核型不知情的实验室人员将该算法应用于第二组数据，以确定 13 三体的风险评分。
在第一阶段，对 11 例 13 三体和 145 例正常二倍体病例进行了 11-13 周妊娠的 13 三体风险评分。该检测识别出 7 例（63.6%）13 三体，无一例假阳性。随后修改了 13 三体算法，在所有 11 例 13 三体中，13 三体风险评分均>99%，在所有 145 例正常二倍体中，风险评分均<0.01%。在第二阶段，使用新算法对 10 例 13 三体和 1939 例正常二倍体病例生成 13 三体风险评分。在 8 例（80.0%（95%置信区间（CI），49.0-94.3%））13 三体病例中，13 三体风险评分>99%。在 1939 例正常二倍体病例中，13 三体风险评分<0.01%的有 1937 例（99.9%），0.79%的有 1 例，>99%的有 1 例。因此，在将样本分类为高风险或低风险的预设风险截断值为 1%时，假阳性率（FPR）为 0.05%（95%CI，0.0-0.3%）。
cfDNA 染色体选择性测序可在 FPR<0.1%的情况下检测出大多数 13 三体病例。
