| Objective: The aim of this study is analyzed the results of clinical validity and utility of noninvasive prenatal testing(NIPT)in 13 852 pregnant women,and compared the results of prenatal diagnosis of pre-NIPT and post-NIPT,in order to evaluate the clinical screening efficacy of NIPT for fetal chromosome aneuploidy,and provide clinical trial data for standardized application of NIPT.Methods: 13 852 pregnant women were slected from October 2015 to September 2017 in the Tianjin Prenatal Diagnosis Center of General Hospital of Tianjin Medical University.Reversible terminal termination method was used for large-scale parallel sequencing.The data were analyzed by bioinformatics software and the results of chromosome aneuploidy were obtained.Prenatal diagnosis was performed on high-risk NIPT samples,followed up to pregnancy outcomes,and low-risk samples were followed up to 1 year postpartum.The samples were grouped according to age,mode of pregnancy,twin pregnancy,results of prenatal serum screening,abortion history,abnormal soft markers of ultrasound and pregnancy complications.The success rate(SR)of NIPT test,detection rate(DR)of chromosome aneuploidy and positive predictive value(PPV)and negative predictive value(NPV)of different groups were compared.Then we slected 2 275 pregnancies from October 2009 to September 2011(pre-NIPT)and 357 pregnancies from October 2015 to September 2017(post-NIPT)respectively,and compared efficacy of prenatal diagnosis between two groups.Results: 1.The SR of NIPT test was 99.87% in 13 852 pregnant women,99.90% in singleton pregnancies and 99.07% in twin pregnancies,99.92% in natural pregnancy and 98.84% in IVF-ET pregnancy,99.90% and 83.33% in non-pregnancy complications and pregnancy complications,respectively.The difference was statistically significant(p < 0.01).The SR of NIPT detection in advanced pregnancies and younger pregnant women were 99.91% and 99.86%,respectively,the SR of NIPT detection in high risk,critical risk and low risk of serological screening were 99.71%,100% and 99.78% respectively,those with and without history of spontaneous abortion were 99.90% and 99.86%,respectively,those with abnormal soft markers of ultrasound and without were 100% and 99.87%,respectively.There was no significant difference in NIPT detection success rate(p > 0.05).None of the pregnant women who used anticoagulant,received immunotherapy and allogeneic blood transfusion,and with tumors during pregnancy had failed NIPT test.2.A total of 54 high-risk cases of 21 trisomy syndrome(T21)were detected by NIPT in 13 834 samples.Among them,49 were chromosome abnormalities.22 were high-risk cases of 18 trisomy syndrome(T18).Among them,15 were chromosome abnormalities,1 was false negative in T18,and 12 were high-risk cases of 13 trisomy syndrome(T13).Among them,7 were chromosome abnormalities.The DR were 100%,94.12% and 100%,PPV were 90.74%,68.18% and 58.33%,NPV were 100%,99.99% and 0%,FPR were 0.36‰,0.43‰ and 0.36‰,sensitivity were 100%,93.75% and 100%,specificity were 99.96%,99.94% and 99.96%,respectively.3.Among 13 834 samples,there were 46 cases with high risk of NIPT in adwanced maternal age,41 cases with chromosomal abnormalities were dectected,PPV was 89.13%,10 598 cases of younger pregnant women,42 cases with high risk of NIPT,30 cases with chromosomal abnormalities and 71.43% of PPV detected.In 245 cases with abnormal soft markers of ultrasound,21 cases were detected with high risk of NIPT,20 cases were chromosomal abnormalities,and PPV was 95.24%,in 12 589 cases without abnormal soft index of ultrasound,NIPT detected 67 cases with high risk,52 cases with chromosomal abnormalities,and PPV was 76.12%.There was significant difference between the groups(p< 0.05).698 high risk cases of serological screening was detected 11 cases in high risk of NIPT,8 cases were chromosomal abnormalities,and was 72.73%.753 cases critical risk was detected 4 cases with high risk of NIPT,2 cases were chromosomal abnormalities,and PPV was 50%.There was no statistical difference between the two groups.4.In 13 834 samples,66 cases of sex chromosome aneuploidy(SCA)were detected by NIPT,26 cases with X chromosome duplication,37 cases with X chromosome deletion and 3 cases with Y chromosome duplication were dected.Prenatal diagnosis was made in 35 of them.10 cases(10/35,28.57%)of fetal chromosome abnormalities were found,11 cases(11/35,31.43%)of maternal chromosome abnormalities were found.5.In the pre-NIPT group,there were 2 275 fetuses,73 cases of chromosomal abnormalities were detected,the abnormal rate was 3.21%.29 cases of T21,7 cases of T18,0 case of T13 and 1 case of SCA were detected.In the post-NIPT group,357 cases of prenatal diagnostic fetuses,183 cases of chromosomal abnormalities were detected.The abnormal rate was 51.26%.102 cases of T21,22 cases of T18,3 cases of T13 and 39 cases of SCA were detected.Conclusion: 1.NIPT test has higher SR,PPV,sensitivity,specificity and lower FPR,which significantly improves the screening efficiency of fetal chromosome aneuploidy.2.The development of NIPT has reduced the number of cases of amniocentesis and the occurrence of adverse reactions caused by amniocentesis,and the DR of chromosomal aneuploidy fetuses has increased.NIPT increased the DR of fetal SCA.3.Pregnant women with prenatal diagnostic indications such as high risk of serological screening,abnormal soft markers of ultrasound and advanced maturnal women can do NIPT,and then make prenatal diagnosis if the results are high risk.twin pregnancy,IVF pregnancy,pregnancy complications and complications of tumors,history of spontaneous abortion,pregnancy with anticoagulant,immunotherapy and allogeneic blood transfusion and so on,NIPT test can be preferred without serological screening. |
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