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.