| Background: The prevalence of twin pregnancies is steadily increasing due to the increasing need for fertility in older women and the widespread use of assisted reproductive technologies.Noninvasive prenatal testing(NIPT)is increasingly used for prenatal screening of twin pregnancies,and its efficacy in screening for chromosomal abnormalities needs to be further evaluated.For twin pregnancies with indications for prenatal diagnosis,there is a lack of clinical data to assess the implementation of prenatal diagnosis.In addition,for invasive prenatal diagnosis,the clinical applicability of karyotype and copy number variation(CNV)analysis in twin pregnancies needs to be further evaluated.Objective: The purpose of this study is to evaluate the screening performance of NIPT for fetal chromosomal abnormalities in twin pregnancies,and also to evaluate the implementation of prenatal diagnosis for those who are recommended for prenatal diagnosis due to NIPT abnormalities or ultrasound abnormalities in the second and third trimesters.For twin pregnancies with amniocentesis in the second and third trimesters,we evaluated the detection rate of chromosomal abnormalities by karyotype and CNV analysis,in order to guide the treatment of prenatal diagnosis of twin pregnancies in the future.Methods:(1)The general clinical data,ultrasonographic(USG)findings,prenatal diagnosis results and pregnancy outcomes of twin pregnancies who underwent NIPT in the prenatal diagnosis center of Xiangya Hospital from January 2018 to December 2022 were prospectively collected to evaluate the screening performance of NIPT for fetal chromosomal abnormalities.With the combination of NIPT results and USG findings,twin pregnancies were divided into the following groups:(1)Group A: twin pregnancies with NIPT results indicating a high risk of abnormalities;(2)Group B: twin pregnancies with NIPT results indicating a low risk of abnormalities and USG findings for one of the twins;and(3)Group C: twin pregnancies with NIPT results indicating a low risk of abnormalities and USG findings for both twins.For twin pregnancies who were recommended for prenatal diagnosis due to abnormal NIPT results or abnormal USG findings in the three groups,the prenatal diagnosis rates(PDRs)and prenatal diagnosis results were followed up to evaluate the implementation of prenatal diagnosis of twin pregnancies.(2)The general clinical data,prenatal diagnostic indications,USG findings,prenatal diagnosis results and pregnancy outcomes of pregnant women who underwent amniocentesis in twin pregnancies during the same period were retrospectively collected to assess the additional detection rate of chromosomal abnormalities by CNV analysis over karyotype analysis.We also analyzed the detection rate of chromosomal abnormalities in different prenatal diagnostic indications,USG findings,chorionicities,conception modes and age groups(35 years as the cut-off).Results:(1)In 1918 twin pregnancies,15 cases with NIPT results indicating high risk were detected: 4 cases of true positive and 1 case of false positive for trisomy 21;1 case of false positive for trisomy 18;2 cases of true positive and 2 cases of false positive for sex chromosome aneuploidy;2 cases of false positive for microdeletion/microduplication syndrome;3 cases refused prenatal diagnosis.The PDR in the abnormal NIPT group(Group A)was 80%.The sensitivity,specificity and positive predictive value of NIPT screening for trisomy 21 were 100%,99.9% and 80.0%,respectively.The corresponding values of NIPT screening for sex chromosome aneuploidy were 100%,99.9% and 50.0%,respectively.(2)Among 561 twin pregnancies with NIPT results indicating low risk,there were 169 cases of pregnancies with USG findings for one of the twins(Group B),of which 64 cases were recommended for prenatal diagnosis.The PDRs of different USG findings ranged from33.3% to 85.7%,and the total PDR was 51.6%(33/64),and 5 cases of variants of uncertain significance(VUS)were detected.In addition,there were 67 cases of pregnancies with USG findings for both of the twins(Group C),of which 39 cases were recommended for prenatal diagnosis.The PDRs of different USG findings ranged from 44.4% to55.6%,and the total PDR was 51.3%(20/39),and 2 cases of VUS were detected.There was no significant difference in the total PDR among Group A,Group B,and Group C.(3)In 538 prenatal diagnostic samples of twin pregnancies,the overall detection rate of fetal pathogenic/likely pathogenic results was3.7%(20/538)(2.4% for aneuploidy,0.9% for pathogenic CNV,and0.4% for likely pathogenic CNV)and the detection rate of VUS was8.4%(45/538).According to the USG findings,538 fetuses were divided into the normal ultrasound group and abnormal ultrasound group.The detection rates of pathogenic/likely pathogenic results in the normal and abnormal ultrasound group were 1.5%(4/269)and5.9%(16/269),respectively,and the difference in detection rates between the two groups was statistically significant.Therefore,the detection rate of pathogenic/likely pathogenic results in the abnormal ultrasound group was higher than that in the normal ultrasound group.(4)In 372 prenatal diagnostic samples of twin pregnancies with both karyotype and CNV analysis,CNV analysis increased the detection rate of pathogenic/likely pathogenic CNV by 1.6%(6/372)and VUS by 8.3%(31/372)compared with karyotype analysis.According to the USG findings,372 fetuses were divided into the normal ultrasound group and abnormal ultrasound group.Compared with karyotype analysis,CNV analysis in the normal ultrasound group did not increase the detection rate of pathogenic/likely pathogenic CNV and increased the detection rate of VUS by 8.5%(17/201);CNV analysis in the abnormal ultrasound group increased the detection rate of pathogenic/likely pathogenic CNV by 3.5%(6/171)and VUS by8.2%(14/171).In fetuses with ultrasound structural malformations and normal karyotype analysis,CNV analysis increased the detection rate of pathogenic/likely pathogenic CNV by 4.4%(2/45)and VUS by6.7%(3/45).(5)In 538 prenatal diagnostic samples of twin pregnancies,there was no significant difference in the detection rate of pathogenic/likely pathogenic results between the dichorionic and monochorionic groups,the in vitro fertilization and natural conception groups,and the low and high age groups.Conclusion:(1)NIPT has a high screening performance for trisomy 21 in twin pregnancies and is suitable for clinical application.NIPT has a good screening performance for sex chromosome aneuploidy in twin pregnancies,but clinical data need to be accumulated to further evaluate its application.(2)When abnormal NIPT results or USG findings are used as the main prenatal diagnostic indicator in the second and third trimesters,the PDR is poor.(3)The results of prenatal diagnosis of twin pregnancies show that the detection rate of chromosomal abnormalities in the abnormal ultrasound group is higher than that in the normal ultrasound group.When USG findings reveal fetal structural malformations and karyotype analysis are normal,CNV analysis increases the detection rate of pathogenic/likely pathogenic CNV similar to that of singleton pregnancy. |
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