| ObjectiveThrough analyzing the detection results of cell-free fetal DNA from peripheral blood in pregnant women,we want to evaluate the screening efficiency of trisomy21(T21),trisomy 18(T18),trisomy 13(T13)and sex chromosome aneuploidy(SCA),and explore the clinical application value.In order to provide scientific basis for prenatal genetic counseling and reduce birth defects and improve the quality of population.Materials and MethodsThe data collected from prenatal diagnosis center of Maternal and Child Health Hospital of Fujian Province during January 1,2015 to September 30,2016.There were6978 cases of pregnant women who received prenatal detection of cffDNA in maternal peripheral blood,eliminated 12 cases of detection failure,to analyze the 6966 cases of pregnant women,ages were(31.60±5.01)years old and pregnant weeks were(18.71±3.13).According to the priority indications,they could be divided into groups of serological screening critical risk,serological screening high risk,advanced maternal age(pre production period is over 35 years old),ultrasound abnormalities,adverse pregnancy history,and others(including missed serological screening or voluntary testing).And divided into two groups of natural conception group and IVF group according to the different conception method.Maternal peripheral blood 10 ml,which were sented to the Jiahui genetics specialist hospital of Hunan Province.High-throughput sequencing(HTS)were used to detect fetal chromosome abnormalities.For pregnant women,those who with high risk of detection result,after getting their informed consent,we performed invasive prenatal diagnosis and fetal karyotype analysis for them.Followed-up all of pregnant women by telephone,in order to know the pregnancy outcomes and the situation of fetal after they birthed.Results1.We detected 108 cases of high risk from 6966 cases of pregnant women and about 93 cases of them performed invasive prenatal diagnosis and fetal karyotype analysis.There were 28 cases of T21 high risk,24 cases had chromosome karyotype of47,XN,+21,and 4 cases were 46,XN.There were 14 cases of T18 high risk,6 cases had chromosome karyotype of 47,XN,+18,and 7 cases were 46,XN,and 1 case was induced labor because of accidental falls,not walking karyotype analysis to confirm.There were 8 cases of T13 high risk,5 cases had chromosome karyotype of 47,XN,+13,and 3 cases were 46,XN.There were 55 cases of SCA high risk,41 cases of them further performed fetal karyotype analysis,about 3 cases of 45,XO,4 cases of47,XXX,4 cases of 47,XXY,5 cases of 47,XYY,and 4 cases of sex chromosome mosaicism,the other 21 cases had normal karyotype.There were 3 cases of high risk in other chromosome aneuploidies,1 case of Chr14-,1 case suspected of 22/1/12 chromosome single or partial deletion,and 1 case of Chr20-,all of them were confirmed to be normal.2.The overall sensitivity of fetal chromosome aneuploidy detection was 100%,the specificity was 99.45%,the false positive rate was 0.55%,the positive predictive value was 59.14% and the negative predictive value was 100%.In addition,the sensitivity of T21 、 T18 、T13 and SCA was all 100%,the specificity was 99.94%,99.90%,99.96% and 99.70% respectively,the false positive rate was 0.06%,0.10%,0.04%,0.30% respectively,the positive predictive value was 85.71%,46.15%,62.50%,48.78% respectively,the negative predictive value was all 100%.3.The abnormal rates of fetal chromosome aneuploidy of serological screening critical risk,serological screening high risk,advanced maternal age,ultrasound abnormalities,adverse pregnancy history and others were 0.60%、1.02%、0.98%、0.55%、0.50% and 0.51% respectively.By the way,the rates of soft index abnormalities and fetal structural abnormalities were 0% and 6.25% respectively.4.In the IVF group,4 cases of chromosome aneuploidy were detected,and the abnormal rate of chromosome aneuploidy was about 1.83%.Compared with natural conception group,there was no significant difference between the two groups(2=3.139,P=0.076).5.The pregnant women with high risk of peripheral blood cffDNA results were followed up in 106 cases,loss of follow-up in 2 cases,follow-up rate of 98.15%.The karyotype analysis confirmed 55 cases of abnormal chromosome,in which there were induced labor in 48 cases,another 3 cases of 47,XYY,2 cases of 47,XXY,1 case of 47,XXX and 1 case of 45,X[12]/46,XX[90] were not found to be abnormality in the fetus after birth.The karyotype analysis was normal in 38 cases,and there was no abnormality found in the fetus after birth in 36 cases,and 2 cases were lost.Refused to invasive prenatal diagnosis in 15 cases,13 cases of SCA high risk were normal in the fetus after birth,1 case of T18 high risk for accidental falls abortion,1 cases of SCA high risk for cervical insufficiency abortion.There were 6858 cases with low risk,and 6581 cases were followed up,the follow-up rate was 95.96%.Among them,1387 cases of pregnant women have not yet been delivered.7 cases miscarried,the rate was 0.13%.Fetal death in 9 cases,the rate was 0.17%.Congenital malformation in 12 cases,the rate was 0.23%.6cases died after birth,the mortality rate was about 0.12%.Conclusion1.The detection techniques of cffDNA from pregnant women’s peripheral blood has the advantages of high sensitivity,high specificity and low false positive rate.The positive predictive efficiency of T21,T18,T13 and SCA was 85.71%,46.15%,62.50%,48.78% respectively.2.This techniques was significant in fetal chromosome aneuploidy for serological screening critical risk,serological screening high risk,advanced maternal age,ultrasound abnormalities,adverse pregnancy history,and those who missed serological screening or voluntary testing.It can reduce the occurrence of missed diagnosis,and avoid unnecessary invasive prenatal diagnosis by more than 98%,and ease the psychological pressure of pregnant women.3.It must to emphasize that the advantages and limitations of the detection technology should be fully informed for pregnant women and their family members in prenatal genetic counseling.They can accord to their own circumstances,voluntary choice the detection methods.Give play to the technical advantages and avoiddisadvantages,it can better strengthen the two prevention of birth defects,improve the quality of the population. |
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