Noninvasive prenatal screening is more effective in screening for fetal aneuploidy than does traditional serological screening. We attempted to analyze the real-world data about the positive predictive value (PPV) for chromosome aneuploidy, and chromosome copy number variation (CNV) obtained by noninvasive prenatal testing (NIPT) , and to explore the pregnancy outcome for fetuses with sex chromosome aneuploidies and chromosome microdeletion or microduplication determined by pregnant women.

To assess the clinical value of karyotype analysis and chromosomal microarray analysis (CMA) of the testing results of NIPT.

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.

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) , respectively, showing statistically significant difference (χ²=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.

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.

无创产前筛查针对胎儿非整倍体的筛查效率明显高于传统的血清学筛查方式，本研究试图获得真实的无创产前基因检测（NIPT）筛查染色体非整倍体及染色体拷贝数变异（CNVs）的阳性预测值（PPV）数据，并初步探讨孕妇对于性染色体非整倍体及染色体微缺失、微重复胎儿的妊娠选择。

评估应用胎儿染色体核型分析、染色体微阵列分析（CMA）明确NIPT筛查提示高风险病例的临床意义。

选择2014-01-01至2018-12-31就诊于河北省人民医院生殖遗传科，经无创产前筛查提示胎儿染色体非整倍体高风险以及胎儿CNVs高风险而需进行产前诊断的528例孕妇为研究对象。经羊膜腔穿刺或脐静脉穿刺获取胎儿细胞，进行染色体核型分析、CMA的产前诊断。对所有分娩病例在1年内进行电话随访，记录其妊娠结局。

NIPT提示528例胎儿中447例为染色体非整倍体高风险，产前诊断的PPV分别为21-三体82.86%（174/210）、18-三体51.52%（34/66）、13-三体12.50%（4/32）、性染色体非整倍体50.82%（62/122）、其他类型三体5.88%（1/17）。NIPT提示81例为CNVs高风险，CMA发现拷贝数变异28例（PPV为34.57%），CMA有明确致病意义者占24.69%（20/81）。<35岁和≥35岁孕妇经产前诊断明确结果异常的比例分别为48.51%（147/303）、70.22%（158/225），<35岁和≥35岁孕妇产前诊断结果异常率比较，差异有统计学意义（χ²=24.938，P<0.05）。62例确诊为胎儿性染色体非整倍体的孕妇中，继续妊娠率为20.97%（13/62）；CMA无明确意义8例，其中1例失访、7例选择继续妊娠（1例婴儿具体情况未告知；1例女婴，双手为六指；余5例婴儿发育正常）。

本研究获得了真实的NIPT筛查染色体非整倍体及CNVs的PPV数据和妊娠结局随访情况，为临床遗传咨询及处理提供了可靠的依据；无创高风险提示染色体存在可疑异常（染色体偏多/偏少/微缺失/微重复）时，建议同时行染色体核型及CMA检查，以便发现染色体倒位、平衡易位、低比例嵌合以及某些形态上的异常，提高胎儿染色体异常的检出率。