| Background: Chromosomal diseases include abnormal chromosome number and abnormal chromosomal structure.Chromosomal aneuploidy disease mainly refers to abnormal chromosome numbers.Chromosomal structural abnormalities include microdeletion,microduplication,chimerism,etc.NIPT has been confirmed by a large number of studies at home and abroad in the screening of foetal chromosomal abnormal diseases has a high sensitivity,specificity and PPV,but there are still relatively few studies to prove the feasibility and clinical application of NIPT in screening foetal chromosomal abnormality in twin pregnancies.Therefore,this study analyzed the application of NIPT in prenatal screening of twin pregnancies to provide evidence for NIPT in prenatal screening of chromosomal abnormalities in twin pregnancies.Objective: To investigate the clinical value of NIPT to screen for chromosomal abnormalities in twin pregnancies and to provide further data on NIPT manifestations in twin pregnancies.Methods: This was a prospective clinical study of 1048 twin pregnancies;the pregnant women underwent NIPT at the Maternity and Child Health Hospital of Anhui Province from March 1,2016,to September 1,2020.The inclusion criteria were as follows:（1）twin pregnancy confirmed by B ultrasound;（2）strong desire for NIPT;and（3）gestational age ≥12 weeks.The exclusion criteria were as follows:（1）pregnant women who received allogeneic blood transfusion,transplantation surgery,cell therapy or other possible interference with NIPT results and（2）definite chromosomal abnormalities in one member of the couple.Results:（1）The results of NIPT screening for the chromosomal abnormalities in twin pregnancies: Thirteen pregnant women with twin pregnancies had NIPT-positive results.There were 2 cases of trisomy 21（T21）,1 of trisomy 18（T18）,7 of sex chromosome aneuploidy（SCA）（45,X: 5;47,XXX: 1;47,XXY: 1）,1 of microdeletion,and 2 of microduplication.No trisomy 13（T13）was detected.Of these 13 cases,2 were true-positive cases confirmed by foetal karyotype analysis,namely,1 case of T21 and 1of microdeletion.Furthermore,the remaining 11 high-risk pregnant women were confirmed as false positive by foetal karyotyping.Thus,the combined positive predictive value（PPV）of NIPT screening for chromosomal abnormalities in twin pregnancies was 15.4%（2/13）.（2）PPV of NIPT in different chromosomal abnormalities: the PPV of screening common trisomy was 33.3%（1/3）,the PPV of screening T21 was 50%（1/2）,and the PPV of screening chromosomal microdeletion and microduplication was 33.3%（1/3）.（3）Follow-up of pregnancy outcomes: All the pregnant women were followed up by telephone or electronic case record systems.Follow-up included pregnancy outcome,physical examination of the new-born and clinical and/or genetic diagnosis of any abnormalities.Thirteen pregnant women with twin pregnancies had NIPT-positive results.All of these women underwent an invasive prenatal diagnosis procedure and confirmation of the foetal karyotype after being informed of the process;they received genetic counselling by clinical geneticists.Microarray analysis of the microdeletions or microduplications was performed.Based on the NIPT and karyotyping results,a foetal reduction operation of the abnormal foetus was performed in the true-positive cases of T21 and microdeletion.The 11false-positive cases decided to continue their pregnancies,and eventually all gave birth to twins with a normal phenotype.Among the 1035 women with NIPT-negative results,1016（98.2%）had follow-up results,and 19（1.8%）were lost to follow-up.A total of977 pregnant women（94.4%）gave birth to twins with apparently normal phenotypes.Twenty-eight women（2.7%）were reported to have adverse pregnancy outcomes with no typical phenotype of chromosomal disease or mental retardation based on follow-up by telephone or through our electronic case record system.Another 11 women had unexplained miscarriages and embryonic arrest.No false-negative results were reported via our follow-up investigations.（4）The reason analysis of the false-positive NIPT results: Studies have shown that NIPT screening cannot completely avoid false-positive results due to confined placental mosaicism,maternal mosaicism,chromosome copy number variation,and maternal tumours,among other confounders.Therefore,when NIPT results are inconsistent with karyotype results,clinicians should be patient in the process of interpretation.We suggest that clinicians should reasonably guide high-risk pregnant women to verify the result by amniotic fluid puncture with the Z value,cff DNA concentration,and B ultrasound.（5）Eight women in this study were tested again after giving consent because the concentration of cff DNA was too low,and the resampling rate was 0.76%（8/1048）.Conclusions:（1）NIPT,based on high-throughput sequencing,is a screening technique rather than a diagnostic technique and is weaker in twin pregnancies than in singleton pregnancies.（2）Safe and rapid NIPT has a certain clinical application value;however,the PPV is limited,and the screening efficiency is not stable.Careful use should be made in the screening of chromosomal abnormalities in twin pregnancies.（3）The screening efficiency of NIPT for autosomal diseases is better than that for sex chromosomal diseases in twin pregnancy. |
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