Department of Prenatal Diagnosis Center, Dongguan Maternal and Child Health Hospital, Dongguan, 523112, Guangdong, China.
CapitalBio Genomics Co., Ltd., Dongguan, 523808, China.
Hum Genomics. 2020 Jun 5;14(1):21. doi: 10.1186/s40246-020-00268-2.
Cell-free fetal DNA (cffDNA) has opened up new approaches for non-invasive prenatal testing (NIPT), and it is often used as the second-tier test for high-risk pregnant women in detecting trisomy (T) 21, T18, and T13 after serum biochemistry screening. This study aims to discuss the clinical performance of NIPT as an alternative first-tier screening test for pregnant women in detecting T21, T18, T13, and sex chromosome aneuploidies (SCAs) in China.
A total of 42,924 samples were recruited. The cell-free plasma DNA was directly sequenced. Each of the chromosome aneuploidies of PPV was analyzed. A total of 22 placental samples were acquired, including 14 FP and 8 TP samples. The placental verification of FP NIPT results was performed.
Among 42,924 samples, 281 (0.65%) positive cases, including 87 of T21, 31 of T18, 22 of T13, and 141 of SCAs were detected. For the detection of T21, the positive predictive value (PPV) was 78.46%, for trisomy 18, 62.96%, for trisomy 13, 10.00%, for SCAs, 47.22% in the total samples. For trisomy 21, the PPV was 86.67%, for trisomy 18, 80.00%, for trisomy 13, 20.00%, for SCAs, 56.52% in advanced maternal age (AMA) women. The PPV of T21 increased with age. For T18, the PPV showed an overall upward trend. For T13 and SCAs, PPV was raised first and then lowered. Placental verification of false positive (FP) NIPT results confirmed confined placental mosaicism(CPM) was the reason for false positives.
This study represents the first time that NIPT has been used as a first-tier screening test for fetal aneuploidies in a pilot city with large clinical samples in China. We propose that NIPT could replace serum biochemistry screening as a first-tier test.
游离胎儿 DNA（cffDNA）为非侵入性产前检测（NIPT）开辟了新途径，它通常被用作血清生化筛查后对高危孕妇进行三体（T）21、T18 和 T13 检测的二线检测。本研究旨在探讨 NIPT 作为中国孕妇检测 T21、T18、T13 和性染色体非整倍体（SCAs）的替代一线筛查试验的临床性能。
共募集 42924 例样本。直接对游离血浆 DNA 进行测序。对每种染色体非整倍体的阳性预测值（PPV）进行分析。共获得 22 例胎盘样本，包括 14 例 FP 和 8 例 TP 样本。对 FP NIPT 结果进行胎盘验证。
在 42924 例样本中，检测到 281 例（0.65%）阳性病例，包括 87 例 T21、31 例 T18、22 例 T13 和 141 例 SCA。T21 的阳性预测值（PPV）为 78.46%，T18 为 62.96%，T13 为 10.00%，总样本中 SCA 为 47.22%。T21 的 PPV 为 86.67%，T18 为 80.00%，T13 为 20.00%，AMA 妇女的 SCA 为 56.52%。T21 的 PPV 随年龄增长而增加。T18 的 PPV 呈总体上升趋势。T13 和 SCA 的 PPV 先升高后降低。对假阳性（FP）NIPT 结果进行胎盘验证证实局限性胎盘嵌合体（CPM）是假阳性的原因。
本研究首次在中国一个具有大量临床样本的试点城市将 NIPT 作为胎儿非整倍体的一线筛查试验。我们提出 NIPT 可以取代血清生化筛查作为一线检测。
