NIPT screens the ppv of fetal chromosomal aneuploidy and pregnancy follow-up
This study found that the positive predictive values of further prenatal diagnosis for pregnant women with high NIPT risk were 85.24% (174/210) of 21-trisomy, 51.52% (34/66) of 18-trisomy, and 12.5% (4/32) of 13-trisomy, other types of trisomy 5.88% (1/17). Petersen et al.  In the test of 712 samples, the PPV of NIPT for 21-trisomy, 18-trisomy, and 13-trisomy were 84%, 76%, and 45%, respectively. Chen et al.  found that the PPV of NIPT for trisomy 21, trisomy 18, and trisomy 13 were 79.24%, 54.84% and 13.79%, respectively. Hu et al.  found that the PPV of NIPT for trisomy 21, 18, and 13 was 80%, 60% and 14.28%, respectively. Some previous studies reported that the PPV range of trisomy 21 was 65–94%, trisomy 18 was 47–85%, and trisomy 13 was 12–62% [9–11]. There is no difference between this study and the literature reports. Big. The number of trisomy 13 and other types of chromosomes is relatively small, and the differences in various literature reports are slightly larger. In this study, the positive predictive values of trisomy 13 and other types of chromosome trisomy were only 12.5% and 5.88%.
The karyotype of a fetus was 45, XN, ? der(18t)(18;21)(p11;q10), -21, the parents chose to continue the pregnancy and gave birth to a girl. There is no abnormality in the current development. 4 cases of fetus with karyotype 47, XN, + 18, check the appearance after induction of labor, 1 case of right foot varus, thick back of the neck, 1 case of six fingers, 1 case of appearance of bruising, 1 case of abnormal ear morphology, more frequently in children with trisomy 18 The external phenotype is abnormal. The karyotype of one fetus was 47, XN, + 13/46, XN. The parents decided to continue the pregnancy and gave birth to a girl with normal development.
NIPT to screen the ppv of fetal sex chromosome aneuploidy and follow-up of pregnancy
The incidence of sex chromosomal aneuploidy (SCA) in newborns is 1/1200 ~ 1/400, and the incidence in the fetal period is as high as 1/435 . The common type of SCA has a single sex chromosome. Sex chromosome (45, X), sex chromosome trisomy (47, XXX, 47, XXY and 47, XYY), other aneuploidies and various forms of mosaic sex chromosome abnormalities . However, NIPT has been controversial about the accuracy of SCA testing. Petersen et al.  In the test of 712 samples, the PPV of NIPT for 45, X, 47, XXX and 47, XXY was 26%, 50% and 87%, respectively. Wang et al.  found that the PPV of NIPT for SCA was only 38% (6/16) in the study of 109 samples tested. Xiong et al.  confirmed from the study of 35827 patients that the PPV of NIPT for SCA was 48.5% (32/66). Zhang et al.  studied 10 275 samples and found that the PPV of NIPT for SCA was 54.54% (18/33). Porreco et al.  confirmed that the PPV of NIPT for SCA was 48.4%. In this study, 528 cases of NIPT positive samples were studied. The results showed that the PPV of NIPT for SCA was 50.86% (64/122), which was closer to the results of Xiong, Zhang, Porreco, etc. [15–17], and 47, XXY was better than others. Chromosome karyotypes are more common, accounting for 51.62% (32/62). The study of Xiong  also confirmed that 47, XXY in SCA can account for 46.9% (15/32).
The phenotypes of SCA patients are diverse, and patients may have no abnormal phenotypes throughout their lives, such as 47, XXX and 47, XYY . Some phenotypes are very mild, and the clinical prognosis is relatively good, which can be manifested as abnormal height development, abnormal organ structure, abnormal behavior, underdevelopment, and hypoplastic secondary sexual characteristics . Of the 62 pregnant women diagnosed with fetal SCA in this study, 2 cases had karyotypes of 47, XXX, 4 cases of 47, XXY, 4 cases of 47, XYY (1 case was born prematurely at 7 months of pregnancy, and died due to pulmonary dysplasia ), low proportion of mosaic 3 cases all chose to continue pregnancy, 49 cases chose to terminate the pregnancy, the overall continued pregnancy rate was 20.97% (13/62). In a study of 399 fetal SCA cases in Hong Kong, So et al.  found that more than half of pregnant women chose to terminate their pregnancy (the overall pregnancy termination rate was 55.6%). A study by Xiong  showed that 50% of pregnant women whose fetuses were SCA screened by NIPT can accept this result (the overall continued pregnancy rate is 50%). Among the pregnant women diagnosed with SCA in this study, 20.97% chose to continue their pregnancy, which was significantly lower than the 40–50% overall continued pregnancy rate of Xiong and So[15, 18]. So is located in Hong Kong and bear is located in Shanghai, Hong Kong and Shanghai are both economically developed areas, families have higher education levels, pregnant women and their families have higher awareness and acceptance of diseases, so the overall continued pregnancy rate is also higher.
CMA detects the advantages and disadvantages of fetal chromosome copy number variation and follow-up of pregnancy
Chromosomal microdeletion and microduplication are a chromosomal disease that causes normal gene imbalance due to submicroscopic chromosome deletion or duplication. It is another important genetic factor for fetal birth defects , accounting for about 15% of all genetic diseases . Its clinical manifestations are complex and changeable, which can cause clinical symptoms such as fetal developmental delay, mental retardation, multiple malformations of internal organs and external phenotypes, and because less fatal genes are involved, the mortality rate after birth is not high, and it can survive long-term disability, giving society and families the burden of weight-bearing is worthy of the attention of birth defect prevention and control workers. Traditional karyotype analysis is the gold standard for diagnosing large fragments and abnormal numbers of chromosomes, but it is difficult to distinguish chromosomal mutations below 5Mbp, and karyotype analysis is also affected by the subjective judgment ability of technicians. When diagnosing small fragments of CNVs Often powerless. CMA technology is a newly developed molecular detection technology that can scan at the whole genome level and has outstanding advantages in detecting chromosomal imbalance abnormalities. It has become the main technology platform for detecting CNVs at this stage. In this study, NIPT showed that 81 fetuses at high risk of CNVs were tested for karyotype and CMA. Among them, 17 cases had abnormal karyotype and CMA, and 11 cases had normal karyotype and abnormal CMA. The positive rate of CMA test could reach 34.57% (28/81), of which CMA has a clear pathogenic significance in 20 cases, which can reach 24.69% (20/81). Jiang et al.  performed CMA on 52 pregnant women with a high risk of CNV s in the NIPT sample, and detected 15 cases of copy number variation that were more consistent with the NIPT results, with a positive rate of 28.85%. Hu et al.  verified the pregnant women whose NIPT indicated a high risk of CNVs, and the PPV was 36.11%. Chen et al.  verified that pregnant women whose NIPT indicated a high risk of CNVs had a PPV of 28.99%. The results of this study are consistent with those of Chen, Hu, and Jiang [7, 8, 21]. In this study, 11 cases of fetal karyotype and CMA were abnormal, of which 1 case was born with karyotype 46, XN, dup (15) (q21.2q22.2), chip 15q21.2q22.2 12 Mb duplication, There are reports of cases where the repetition of less than this fragment is associated with clinical phenotypes such as hydrocephalus, microcephaly, and overall developmental delay. The child is currently well-developed. Among the 10 cases of labor induction, 1 case had a karyotype of 46, XN, add (2) (p25.3), a chip of 2p25.3 × 1 1.9 Mb deletion, and 2p25.3p23.1 × 3 28.4 Mb duplication. No abnormalities in the couple Fish; 1 case of karyotype is 46, XN, add(21) (p10), chip is 10p15.3p12.1 × 3, 26.62 Mb duplication, pregnant woman karyotype is 46, XX, t(10; 21) (p10 ;q10); 1 case of karyotype 46, XN, del(5) (p13.2p15.3), chip 5p15.33p13.2 × 1 35.7 Mb deletion, 5q34q35.3 × 3 15.2 Mb duplication (Catscry Syndrome), the pregnant woman has a normal karyotype, and the man’s karyotype is 46, XY, inv(5) (p13.2q34). The karyotype in 1 case is 45, XN, -18/46, XN, i(18) p10/46, XN, i(18)q10, chip 18p11.32p11.21 × 1 14.2 Kb is deletion. The karyotype of one case was 46, XN, del (2) (p25p24), del (2) (p22p21), inv9 (q12q13), the chip was 2p25.1p24.3 × 1 5 Mb deletion and 2p22.3p21 × 1 8 Mb deletion. From the above analysis, when a parent’s chromosome has a balanced translocation or inter-arm inversion, the fetus’s chromosomes are prone to deletion/duplication of large fragments and/or small fragments; there may be discrepancies between the karyotype results and the microarray results. 1 The karyotype is a duplication of chromosome 21, and the chip is a microduplication of chromosome 10; the chip cannot detect a low proportion of mosaicism. In this study, the karyotype is 45, XN, -18/46, XN, i (18) p10 /46, XN, i(18) q10, the chip only detects the microdeletion of chromosome 18, and there are literature reports  that CMA cannot detect the low proportion of chimeras < 10%. This study also can be confirmed; the chip cannot detect balanced translocations and inter-arm inversions of chromosomes with normal copy numbers. In this study, the karyotype is 46, XN, del (2) (p25p24), del (2) (p22p21), inv9 (q12q13), the chip only detects the microdeletion of chromosome 2.
In this study, there were 17 cases with normal fetal karyotype and abnormal chip. Among these 17 cases, the chip had no clear significance/no disease reported in 8 cases, which could reach 9.88% (8/81). Domestic scholar Jiang Yulin and others [ 23] The study found that CNVs of unknown clinical significance in CMA detection accounted for 15.3% of the total number of cases examined. Among these 8 cases, 1 case was lost to follow-up, and 7 cases chose to continue their pregnancy. 1 case had a 2.8 Mb deletion of chromosome 16 and gave birth to a boy, but the specific situation of the child was not informed; 1 case had a duplication of chromosome 18 of 866.4Kb, gave birth to a girl with six fingers on both hands, and no abnormal development was seen in the remaining 5 cases. Normal development. This study shows that: if the CMA results have no clear significance or no disease reports, those who choose to continue pregnancy, except for one child who was not informed about the specific situation, the other children have no obvious mental retardation, will there be other problems such as childbirth in the future, Long-term follow-up is required.