Evaluation Of Noninvasive Prenatal Testing And Chromosome Microarray In The Analysis Of Fetal Chromosomal Abnormalities

Objective:In this study,the clinical data of 13002 pregnant women with informed consent and voluntary noninvasive prenatal testing(Noninvasive prenatal testing,NIPT)screening for fetal chromosomal abnormalities were collected.The results of chromosome karyotype analysis were used as the standard,and the results of NIPT screening were statistically analyzed after sorting and classification.To evaluate the screening efficiency of T21/T18/T13 and the screening effect of sex chromosome aneuploidy(SCA)and chromosome copy number variations(CNVs),for the application of NIPT to fetuses Prenatal screening for chromosomal aneuploidy and future expanded screening accumulate valuable clinical data.At the same time,the accuracy of chromosome CNVs screening via NIPT was verified by single nucleotide polymorphism array(SNP array).Furthermore,feasibility of clinical application of the combination of SNP array and traditional interventional diagnostic methods was discussed,aiming to improve detection rate of fetal chromosomal diseases and reduce the missed diagnosis of children with birth defects caused by genetic diseases,without increasing the risk of invasive diagnosis.Methods:The first part of this study retrospectively collected the data of 13002 singleton pregnant women who underwent NIPT screening for fetal chromosomal aneuploidy at the Prenatal Diagnosis Center of the Affiliated Hospital of Putian University from January 1,2016 to December 31,2020.Age,gestational age,NIPT screening results,prenatal screening indications,screening results of different age groups combined with genetic diagnosis results were statistically analyzed to evaluate the clinical application of NIPT.The second part collects the data of 136 pregnant women who underwent karyotype and SNP chip technology to detect fetal chromosomes due to different prenatal diagnosis indications,and compares the results of karyotype analysis with the results of SNP chip detection to evaluate the use of SNP chip technology in diagnosing fetal chromosomes.The application of abnormalities,while evaluating the accuracy of NIPT screening chromosomal CNVs through SNP chip diagnosis results.Results:1.NIPT screening results of fetal chromosomal abnormalities: comparing NIPT results with interventional genetic diagnosis results,the sensitivity of NIPT screening T21/T18/T13 is calculated to be 100%/100%/0,and the specificity is99.95%/99.98 %/99.98%,the positive predictive value for T21 is the highest(85.71%),and the positive predictive values of extended screening SCA and chromosomal CNVs are 52.63% and 10%;NIPT is different between advanced and non-advanced age,abnormal ultrasound and normal ultrasound.There was no statistically significant difference in the results of screening fetal chromosomal abnormalities among the age groups.2.136 cases detected by SNP chip technology detected 13.24%(18/136)more chromosomal abnormalities than karyotype analysis.The detection rates of the two were significantly different and statistically significant;the non-elderly group and the abnormal ultrasound group were detected by chromosomal karyotypes compared with the results of SNP chip analysis,the difference is significant and statistically significant;NIPT screening of chromosomal CNVs has a high risk and the positive predictive value of SNP chip verification is 50%;the parental family verification can further confirm that most of the fetuses with unclear clinical significance CNVs source.Conclusions:1.Compared with traditional prenatal screening methods,NIPT has higher sensitivity,specificity and positive predictive value in screening fetal chromosomal aneuploidy,and has a low false positive rate.It can be used as an effective supplement for invasive prenatal diagnosis.Eliminates the vast majority of unnecessary interventional diagnosis.At the same time,NIPT detection technology still has false positives.Pregnant women and their families should be informed in detail of the advantages and limitations of this technology during prenatal genetic counseling.NIPT screening high risk should be entered into prenatal diagnosis.2.Compared with chromosome karyotype analysis,the detection rate of SNP chip technology in fetal chromosomal abnormalities is significantly different and statistically significant.Combining the two detection technologies can effectively complement each other.For fetuses with structural abnormalities revealed by prenatal ultrasound,it is recommended direct microarray analysis to replace traditional chromosome karyotype analysis.At the same time,SNP chip technology can detect many CNVs of unknown clinical significance due to high resolution.Family verification can further confirm most of the sources of mutations,reduce unnecessary worries and anxiety of patients and their families,provide a basis for genetic counseling,and prevent birth defects are of great significance.