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中华妇幼临床医学杂志(电子版)

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2021, Vol. 17 ›› Issue (04): 410 -419. doi: 10.3877/cma.j.issn.1673-5250.2021.04.006

Original Article

Analysis of non-invasive prenatal screening in 50 975 pregnant women in Guangxi region

Yaqin Lei, Yunli Lai, Shang Yi, Fuben Xu, Yanqing Tang, Xiaoshan Huang, Jian Yi, Xiaoxia Qiu†()   

  • Received:2020-12-28 Revised:2021-06-11 Published:2021-08-01
  • Corresponding author: Xiaoxia Qiu
  • Supported by:
    Research Program of Health Department of Guangxi Zhuang Autonomous Region(Z20200601); Guangxi Special Fund for Scientific Base and Talent(GKAD17129016)
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Objective

To investigate the clinical performance of non-invasive prenatal testing (NIPS) in the detection of chromosome aneuploidies and genome-wide copy number variation (CNV).

Methods

A total of 50 975 serum specimens from singleton pregnant women who received NIPS at the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2018 to December 2019 were selected into this study. Based on different risk factors, they were divided into 3 groups. Those with serologic screening results of high risk + elderly pregnant women + adverse maternal history/family history were included in high-risk group (n=22 852), those with moderate risk/critical risk of serologic screening and abnormal ultrasound soft indicators were included in moderate-risk group (n=4 584), and those without the above risk factors were included in low-risk group (n=23 539). For those with high risk of NIPS detection, chromosome karyotype analysis and chromosome microarray analysis (CMA) were used for interventional prenatal diagnosis. The study protocol was approved by the Ethics Review Committee of Guangxi Maternal and Child Health Hospital (approval No.[2020]9-2).

Results

① Of 50 975 pregnant women who underwent NIPS, 702 cases showed high risk, with a total positive rate of 1.38%. Among them, the high risk of 21-, 18-and 13-trisomy was 175 cases (0.34%), 67 cases (0.13%) and 63 cases (0.12%), respectively, the high risk of sex chromosome aneuploidy abnormalities (SCA) was 205 cases (0.40%), the high risk of rare chromosome number abnormality (RCA) was 96 (0.19%), and the high risk of copy number variation (CNV) was 96 (0.19%). ②A total of 555 of the 702 positive cases (79.06%) were followed up by karyotyping and (or) CMA, 93 (16.76%) refused confirmatory diagnosis, 42 (7.57%) did not perform prenatal diagnosis because of abortion or induced labor, and 12 (1.71%) lost follow-up. ③The positive predictive values for trisomy 21, trisomy 18, trisomy 13, SCA, RCA, and CNV were 85.09% (137/161), 57.14% (28/49), 16.67% (9/54), 42.31% (66/156), 5.56% (4/72), and 42.86% (27/63), respectively. ④In 16 cases with high risk of NIPS screening, NIPS was not detected by interventional prenatal diagnosis, but other abnormal results were detected. Of the 4 fetuses with high risk of trisomy 21, CNV was detected in 3 and complex structural variation of chromosome 21 was detected in 1. In one case of 18-trisomy high-risk fetus, the karyotype analysis results suggested that it was 21-trisomy. Among the 2 fetuses with 13-trisomy high risk, one was a chimera with chromosome structural variation, and the other was CNV. CNV of other chromosomes was detected in 3 fetuses with high SCA risk and 2 fetuses with high RCA risk. Among the 4 fetuses with high risk of CNV, 47, XYYY were detected in 1 case and other CNV abnormalities were detected in 3 cases.

Conclusions

NIPS has a high clinical value for screening common chromosomal aneuploidies such as 21-, 18-, and 13-trisomies. the positive predictive value of NIPS for screening SCA, RCA and CNV is low, but combined with prenatal ultrasound and other related examination, it can provide a basis for genetic counseling and further prenatal diagnosis.

Key words: Prenatal diagnosis, Non-invasive prenatal screening, Karyotyping, Chromosome microarray analysis, Rare chromosome aneuploidies, DNA copy number variations, Sex chromosomes, Chromosome structures, Pregnant women
表1 3组孕妇NIPS情况[例数(%)]
组别 例数 21-三体 18-三体 13-三体 SCA RCA CNV 合计
高风险组 22 852 121(0.53) 48(0.21) 35(0.15) 86(0.38) 46(0.20) 41(0.18) 377(1.65)
  血清学筛查高风险 3 271 16(0.49) 7(0.21) 9(0.28) 13(0.40) 11(0.34) 7(0.21) 63(1.93)
  高龄 17 216 101(0.59) 37(0.21) 22(0.13) 64(0.37) 32(0.19) 31(0.18) 287(1.67)
  不良孕产史/家族史 2 365 4(0.17) 4(0.17) 4(0.17) 9(0.38) 3(0.13) 3(0.13) 27(1.14)
中风险组 4 584 14(0.31) 2(0.04) 5(0.11) 23(0.50) 10(0.22) 6(0.13) 60(1.31)
  血清学筛查中度风险/临界风险 3 233 9(0.28) 1(0.03) 3(0.09) 21(0.65) 9(0.28) 6(0.19) 49(1.52)
  胎儿超声指标异常 1 351 5(0.37) 1(0.07) 2(0.15) 2(0.15) 1(0.07) 0(0) 11(0.81)
低风险组 23 539 40(0.17) 17(0.07) 23(0.10) 96(0.41) 40(0.17) 49(0.21) 265(1.13)
合计 50 975 175(0.34) 67(0.13) 63(0.12) 205(0.40) 96(0.19) 96(0.19) 702(1.38)
表2 NIPS高风险者进一步进行介入性产前诊断的检测结果
染色体异常 NIPS结果为胎儿高风险例数 介入性产前诊断结果 假阳性率(%) 敏感度(%) 特异度(%) 阳性预测值(%)
阳性 假阳性a
常见CAA 305 174 90 0.18 100.0 99.82 65.91
  21-三体 175 137 24 0.05 100.0 99.95 85.09
  18-三体 67 28 21 0.04 100.0 99.96 57.14
  13-三体 63 9 45 0.09 100.0 99.91 16.67
SCA 205 66 90 0.18 100.0 99.82 42.31
  性染色体数量减少 74 12 43 0.09 100.0 99.91 21.82
  性染色体数量增加 69 38 12 0.02 100.0 99.98 76.00
  性染色体其他异常 62 16 35 0.07 100.0 99.93 31.37
RCA 96 4 68 0.14 100.0 99.86 5.56
  1-单体 1 0 1 0.00 — 100.00 0
  2-三体 2 1 1 0.00 100.0 100.00 50.00
  3-三体 7 0 5 0.01 — 99.99 0
  4-三体 2 0 1 0.00 — 100.00 0
  5-单体 1 0 0 0.00 — 100.00 —
  5-三体 2 0 1 0.00 — 100.00 0
  6-单体 1 0 0 0.00 — 100.00 —
  7-三体 16 1 10 0.02 100.0 99.98 9.09
  8-三体 9 0 7 0.01 — 99.99 0
  9-三体 2 1 1 0.00 100.0 100.00 50.00
  10-三体 6 0 5 0.01 — 99.99 0
  11-单体 1 0 1 0.00 — 100.00 0
  11-三体 3 0 2 0.00 — 100.00 0
  12-三体 1 0 1 0.00 — 100.00 0
  14-单体 7 0 5 0.01 — 99.99 0
  14-三体 3 0 3 0.01 — 99.99 0
  15-三体 4 0 4 0.01 — 99.99 0
  16-单体 2 0 1 0.00 — 100.00 0
  16-三体 12 0 11 0.02 — 99.98 0
  17-三体 2 0 2 0.00 — 100.00 0
  20-三体 5 0 3 0.01 — 99.99 0
  22-三体 7 1 3 0.01 100.0 99.99 25.00
CNV   96 27 36 0.07 100.0 99.93 42.86
表3 16例胎儿NIPS与介入性产前诊断结果不一致
病例(No.) 年龄 孕龄 NIPS胎儿染色体核型异常 介入性产前诊断胎儿染色体核型异常 SNP芯片结果 片段大小(Mb) CNV致病性评估
1 36 16 21-三体高风险 未见数目和结构异常 arr[hg19]21q22.3(44585405-45722442)x3 1.14 临床意义不明
2 37 17+3 21-三体高风险 未见数目和结构异常 arr[hg19]7q11.23(72350815-74138121)x1 1.79 致病
3 35 15 21-三体高风险 未见数目和结构异常 arr[hg19]21q21.2(25114738-26305530)x3 1.19 临床意义不明
4 33 18 21-三体高风险 45，Xn，-21[11]/46，Xn，r(21)(p11q22)[183]/46，Xn，dic r(21；21)(p11q22；p11q22)[6] 未见染色体数目和结构异常 — 致病
5 38 18 18-三体高风险 47，XN，+21 未检测 整条 致病
6 30 18+3 13-三体高风险 45，XY，der(13，13)(q10，q10)[41]/45，XY，der(13，20)(q10，q10)[13]/46，XY[18] 未见染色体数目和结构异常 — 致病
7 26 20+5 13-三体高风险 未见数目和结构异常 arr[hg19]16p13.11(15239631-16289532)x3 1.05 可能致病
8 31 18 性染色体数目减少 未见数目和结构异常 arr[hg19]15q21.3(57080418-57495813)x1 0.42 可能致病
9 32 17+5 性染色体异常 未见数目和结构异常 arr[hg19]3q29(195738406-197409600)x1 1.67 致病
10 37 22+6 性染色体异常 46，X，Yqh- arr[hg19]1q21.1(145384225-145755813)x1 0.37 临床意义不明
11 30 17+4 3-三体高风险 未见数目和结构异常 arr[hg19]9q31.1(104939411-106639645)x1 1.70 临床意义不明
12 27 16+6 7-三体高风险 未见数目和结构异常 arr[hg19]2q13(110982530-113100014)x3 2.12 可能致病
13 35 16+5 11号染色体有重复 47，XYY 47，XYY 整条 致病
14 31 15 20号染色体有缺失 未见数目和结构异常 arr[hg19]8p23.1(9783789-10950866)x3 1.17 临床意义不明
15 24 17 16号染色体有重复 未见数目和结构异常 arr[hg19]22q11.21(21062271-21462353)x3 0.4 临床意义不明
16 27 17 16号染色体有重复 未见数目和结构异常 arr[hg19]21q21.1(19563036-20235268)x1 0.67 临床意义不明
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