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（NIPT），and to explore the pregnancy outcome for fetuses with sex chromosome aneuploidies and chromosome microdeletion or
microduplication determined by pregnant women. Objective To assess the clinical value of karyotype analysis and chromosomal
microarray analysis （CMA） of the testing results of NIPT. Methods Five-hundred and twenty-eight pregnant women who
were found with a fetus at high risk of chromosome aneuploidy，and CNV by NIPT were selected from Department of Reproductive
and Genetic Medicine，Hebei General Hospital，from January 1，2014 to December 31，2018. Amniocentesis or umbilical
vein puncture was performed in them to obtain fetal cells for a definite prenatal diagnosis using karyotype analysis and CMA. All
delivered cases were followed up by telephone within one year after childbirth to understand the pregnancy outcome. Results
Prenatal diagnosis analysis revealed that 447 fetuses were at high risk of chromosome aneuploidy. And PPVs for the risk of trisomy
21，trisomy 18，trisomy 13，sex chromosome aneuploidies，and other chromosome aneuploidy were 82.86%（174/210），
51.52%（34/66），12.50%（4/32），50.82%（62/122），and 5.88%（1/17），respectively. Another 81 fetuses were at
high risk of CNVs. CMA suggested that copy number variations were found in 28 cases （PPV 34.57%），and the proportion
with a clear pathogenic significance reached 24.69% （20/81）. Among the subjects under 35 years and 35 years or older，
the proportions of abnormal results confirmed by prenatal diagnosis were 48.51% （147/303） and 70.22% （158/225），
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respectively，showing statistically significant difference（χ =24.938，P<0.05）. Out of the 62 pregnant women diagnosed with
fetal sex chromosome abnormality，13（20.97%） continued with the pregnancy. Eight cases were reported no clear significance
in CMA，among them one case was lost to follow-up，other seven cases chose to continue pregnancy. Among the seven infants，
five were born healthy and developed normally，one girl had six fingers in both hands and the remaining one's situation was
unknown. Conclusion The real-world data regarding PPVs for chromosomal aneuploidies and CNVs by NIPT，and follow-up
of pregnancy outcome obtained by us，provide a reliable basis for clinical genetic counseling and treatment. It is recommended to
perform karyotype analysis and CMA for a pregnant woman with a fetus with suspected chromosomal abnormality（extra or missing
chromosomes，chromosome microdeletion，or microduplication） suggested by NIPT，to identify chromosome inversion，
balanced translocation，low proportion chimerism and some morphological abnormalities，so as to improve the detection rate of
fetal chromosome abnormalities.
【Key words】 Prenatal diagnosis；Noninvasive prenatal screening；Chromosomal microarray analysis；Sex
chromosome aberrations；Sex chromosome aneuploidy；Copy number variations；Positive predictive value

染色体病是由染色体数目和结构异常引起的疾 儿的妊娠选择，以期为临床遗传咨询及处理提供更多
病，是临床上导致胎儿出生缺陷的常见原因之一，其 参考。
中 21- 三体、18- 三体、13- 三体及性染色体非整倍体 1 资料与方法
（sex chromosomal aneuploidy，SCA）是胎儿染色体非整 1.1 临 床 资 料 选 择 2014-01-01 至 2018-12-31 就
倍体的主要类型，占所有染色体疾病的 80%~90% ［1］ 。 诊于河北省人民医院生殖遗传科，因无创产前筛查提
传统的产前筛查虽具有一定的筛查价值，但存在一定比 示胎儿 21、18、13、性染色体、其他染色体三体非整
例的假阳性与假阴性。无创产前基因检测（non-invasive 倍体高风险以及胎儿染色体拷贝数变异（copy number
prenatal testing，NIPT）是采用新一代高通量测序技术， variations，CNVs）高风险而需要进行产前诊断的孕妇为
+3
利用孕妇外周血中的游离胎儿 DNA 进行胎儿常见染色 研究对象。孕妇年龄 18~47 岁，孕周 18~28 周。所有
体非整倍体筛查，是近年来快速发展起来的安全、高 孕妇无产前诊断穿刺禁忌证，产后（引产后）接受电话
效、易于推广的产前筛查新方式，明显提高了染色体疾 随访，均签署产前诊断知情同意书。本研究通过了河北
病产前筛查的灵敏度和特异度 ［2-3］ 。已有大量研究表明 省人民医院伦理委员会的审核。
NIPT 针对胎儿非整倍体的筛查效率明显高于传统的血 1.2 产前诊断 根据孕周的不同分别抽取羊水或脐血
清学筛查方式 ［4-5］ ，但仍存在一定的假阳性和假阴性， 行胎儿染色体核型分析和染色体微阵列分析（CMA）检
因此目前仅可作为产前筛查方法，尚不能作为产前诊断 测，检测方案、技术利弊由咨询医师详细告知，孕妇知
的方法。 情选择。
本研究回顾性分析了因 NIPT 高风险在河北省人民 1.3 统计学方法 使用 SPSS 22.0 软件进行统计分析，
医院生殖遗传科行产前诊断患者的检测结果及妊娠选 计数资料以相对数表示，组间比较采用 χ 检验。以
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择，计算 NIPT 筛查胎儿染色体非整倍体及微缺失、微 P<0.05 为差异有统计学意义。
重复的阳性预测值（positive predictive value，PPV）， 2 结果
并初步探讨孕妇对于 SCA 及染色体微缺失、微重复胎 2.1 胎儿染色体非整倍体异常类型及构成比 NIPT 提