The Effect Of Non-invasive Prenatal DNA Testing In Screening Fetal Chromosomal Aneuploidy And Its Correlation With Gestational Age,Age And Other Factors

Objective:To analyze the detection effect of non-invasive prenatal DNA testing（NIPT）on common chromosome aneuploidy abnormalities of the fetus in Peking University Shenzhen Hospital,and to explore the correlation between different gestational weeks,maternal age and detection effect indicators.Methods:Pregnant women who underwent NIPT in Peking University Shenzhen Hospital from June 2013 to April 2019 were selected to analyze the chromosome karyotype of amniotic fluid with high risk,and others with low risk were followed-up by telephone.The abnormality of fetus was judged by karyotype analysis and follow-up results,and analyze the NIPT detection effect index.According to the age of pregnant women,they were divided into 4 groups:<30 years old group,30-34 years old group,35-39 years old group,≥40 years old group,and according to the gestational age were divided into 4 groups:≤13⁺⁶weeks group,14-22⁺⁶weeks group,23-27⁺⁶weeks group,≥28 weeks group.And to explore the correlation of sensitivity,specificity,positive predictive value,negative predictive value and false positive rate with pregnant age and gestational age.Results:（1）A total of 43,934 pregnant women underwent NIPT,16 cases were lost to follow-up,and 43,918 cases were included in the statistical analysis.Among them,457were positive,43461 were negative,106 were false positive,and 0 were false negative.The overall sensitivity of NIPT is 100.00%（352/352）,the specificity is99.76%（43,460/43,566）,and the positive predictive value is 76.86%（352/458）,the negative predictive value is 100.00%（43,460/43,460）,and the false positive rate is0.24%（106/43,566）.（2）The sensitivity of NIPT to T21,T18,T13 and sex chromosomal abnormalities is 100.00%（125/125）,100.00%（44/44）,100.00%（17/17）,100.00%（112/112）,the specificity is 99.98%（43,786/43,793）,99.97%（43,863/43,874）,99.97%（43,886/43,901）,99.91%（43,766/43,806）,the positive predictive value is 94.70%（125/132）,80.00%（44/55）,53.13%（17/32）,73.68%（112/152）,the negative predictive value is 100.00%（43,786/43,786）,100.00%（43,863/43,863）,100.00%（43,886/43,886）,100.00%（43,766/43,766）,and the false positive rate is 0.02%（7/43793）,0.03%（11/43874）,0.03%（15/43901）,0.09%（40/43806）.（3）There is no significant statistically difference（P>0.05）in sensitivity,specificity,positive predictive value,negative predictive value and false positive rate among different age and gestational weeks of NIPT.（4）There are 106 false positive cases of NIPT,including 40 cases（40/106）of sex chromosome abnormality,22 cases（22/106）of autosomal abnormality and 11 cases（11/106）of microdeletion and repetition.Among the false positive cases,it was found that 2 cases newborns had congenital heart disease,1 case with slight separation of double renal pelvis and 1 case with multiple abnormalities and other non-chromosomal abnormalities.（5）NIPT showed 152 cases of abnormal number of sex chromosomes.Amniotic fluid chromosome examination showed that sex chromosome number abnormality was found in 112 cases（73.68%）,including 45,X（61cases）,47,XXY（21 cases）,47,XYY（21 cases）,47,XXX（8 cases）,48,XXXY（1case）.NIPT showed 63 cases of abnormal number of chromosomes other than T21,T18,T13 and sex chromosome abnormalities.Amniotic fluid chromosome examination was performed.41 cases of chromosomal abnormalities（65.08%）.NIPT indicated chromosome microdeletions（20 cases）,40 cases of microduplication（20 cases）,40cases of amniotic fluid chromosome karyotype analysis,29 cases（72.50%）of abnormalities,11 cases of no abnormalities.Conclusions:Non-invasive prenatal DNA testing（NIPT）has high accuracy and specificity for common chromosome aneuploidy abnormalities,and low false positive rate,especially for trisomy 21.NIPT has certain detection efficiency for sex chromosome abnormalities and copy number variations.There is no significant difference in the detection effect of NIPT for pregnant women of different ages and different gestational weeks.For the cases with positive NIPT results,it is necessary to guard against the occurrence of fetal non-chromosome abnormalities and other abnormalities.