| Non-invasive prenatal testing（NIPT）was based on the presence of fetal free DNA in maternal plasma,used high-throughput sequencing technology and bioinformatics analysis to detect whether the fetus has chromosome diseases,at present,it had been widely use in the prenatal diagnosis of trisomy 21 syndrome（Trisomy 21 syndrome,T21）,trisomy 18 syndrome（Trisomy 18 syndrome,T18）and trisomy 13syndrome（Trisomy 13 syndrome,T13）.However,in the clinical practice,NIPT was still face great controversy in the prenatal diagnosis of fetal chromosome diseases,such as other autosomal aneuploidies except chromosome 21、18 and 13,SCA and CNV.There were few reports in domestic literature,and still had some challenges in the accuracy and reliability of its detection.National Health Commission issued the 《 notice on standardized and orderly prenatal screening and diagnosis of fetal free DNA in maternal peripheral blood 》 in 2016,for other high-risk results other than the target chromosome（chromosome 21,18 and 13）detected by NIPT,the prenatal diagnosis institution should informed the pregnant woman of further consultation and diagnosis,The complexity of the above chromosome test reports often makes genetic counseling difficult,whether to choose invasive prenatal diagnosis will lead to anxiety in pregnant women,It brings some challenges to clinical workers.The purpose of this study was to analyze the detection results of NIPT in pregnant women,compared it with the results of interventional prenatal diagnosis,analyze its detection efficiency,and explore the clinical application value of NIPT in chromosome diseases.Objective To assess the detection efficiency of noninvasive prenatal testing（NIPT）for fetal autosomal aneuploidy,sex chromosome aneuploidy（SCA）,other chromosome aneuploidy,copy number variation（CNV）,accumulate experience for the clinical application of NIPT.It provides scientific basis for prenatal diagnosis and genetic counseling for pregnant women,and has great significance for the prevention and treatment of birth defects and improving the quality of the population.Methods 25,517 pregnant women who underwent NIPT testing in Anhui Province Maternity and Child Health Hospital from September 2019 to September 2020 were selected,and samples with high-risk test results were subjected to karyotype analysis for comparison by using amniotic fluid,with some samples subjected to further validation by chromosomal microarray analysis（CMA）,and followed up for pregnancy outcome.Results A total of 25,517 pregnant women who received NIPT,25,502 cases were tested,and 294 high-risk samples（1.15%）were detected,there were 96 true positive samples,117 false positive samples and 81 cases were refused further diagnosis.Samples with high risk of autosomal aneuploidy were detected in 71 cases（0.28%）,and 51 cases were confirmed,including: trisomy 21 in 44 cases,trisomy 18 in 5 cases,and trisomy 13 in 2 cases;the positive predictive value（PPV）was 91.67%,45.45%,and 33.33%,respectively,and the negative predictive value（NPV）was100%,the false positive rate（FPR）was 0.02%,0.02%,and 0.02%,respectively.13 samples with high risk of mosaic trisomies 21,18,and 13 were detected,and 1 case of T21 mos was confirmed with a PPV of 8.33%.Samples with high risk of sex chromosome aneuploidy（SCA）were detected in 72 cases（0.28%）,and the diagnosis was confirmed in 23 cases,with a PPV of 41.07% and a FPR of 0.13%.These included3 cases of 45,X,6 cases of 47,XXY,8 cases of 47,XXX and 6 cases of 47,XYY,with PPVs of 12.00%,50.00%,72.73%,and 75.00%,respectively,and false-positive rates of0.09%,0.02%,0.01% and 0.01% respectively.Samples with high risk of copy number variation（CNV）were detected in 104 cases（0.41%）and confirmed in 18 cases,with a PPV of 32.14% and a FPR of 0.15%.Samples with high risk of other autosomal aneuploidies were detected in 34 cases（0.13%）,and the diagnosis was confirmed in 3cases,which were T2,T9,and T16（Trisomy,T）respectively.The overall PPV for other autosomal aneuploidy was 12.50%,with a FPR of 0.08%.Conclusion: NIPT had high accuracy and reliability in screening T21,T18 and T13,especially for T21..NIPT still had certain clinical applicability in the detection of sex chromosome triploid,but the detection efficiency of 45,X is not stable.In some cases of SCAs,there were no obvious clinical phenotype in fetal period,and clinical symptoms will appear only after puberty.Therefore,long-term follow-up is particularly important for the prenatal screening results of SCA by NIPT.NIPT had low detection efficiency for other autosomal aneuploidies（except chromosomes 21,18 and 13）,NIPT test reports the results of other autosomal aneuploidies,pregnant women should be fully informed of their limitations.NIPT was also not recommended for the screening of other autosomal aneuploidies and mosaic chromosome abnormalities.NIPT had certain detection efficiency for CNVs.In particular,the detection of CNV with definite pathogenicity was still of clinical significance,which can provide an important basis for subsequent karyotype analysis or CMA detection. |
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