OBJECTIVE: To evaluate the efficacy of non-invasive prenatal testing (NIPT) in the prenatal screening and its role in the system of prenatal diagnosis. METHODS: A total of 22 649 singleton pregnant women who were registered and finally delivered or had induced labor at Beijing Obstetrics and Gynecology Hospital of Capital Medical University were enrolled. The routes of prenatal screening were analyzed to evaluate the efficacy of prenatal screening. Meanwhile, 9268 pregnant women who underwent invasive prenatal diagnosis procedure were enrolled. The indications and results of prenatal diagnosis were analyzed to evaluate the effectiveness of prenatal screening. RESULTS: 60.24% of singleton pregnant women have opted for Down syndrome screening, and their age was mainly under 35. The proportion of women opted for NIPT was 34.74%, and were mainly between 35 and 39. The overall diagnostic rate of trisomy 21, 18 and 13 trisomy for those with high risk by NIPT was 0.89%, which yielded a positive predictive value of 75.71%. For those with moderate risk by serum screening, 0.30% was predicted with a high risk by NIPT. Among women undergoing prenatal diagnosis, 63.04% and 21.22% had the indication of advanced age or high risk by serum screening, and the positive predictive values were 5.1% and 5.13%, respectively. By contrast, 2.30% of women undergoing prenatal diagnosis had a high risk by NIPT, which yielded a positive predictive value of 54.46%. CONCLUSION With the change of the age composition of pregnant women and increase in the complexity of pregnancy in China, to build a prenatal screening system based on NIPT will be helpful to improve the efficiency of the current system of prenatal screening and diagnosis.
China ; Down Syndrome/genetics* ; Female ; Humans ; Pregnancy ; Prenatal Diagnosis ; Trisomy 13 Syndrome ; Trisomy 18 Syndrome

OBJECTIVE: To explore the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with high risk signaled by non-invasive prenatal testing (NIPT). METHODS: From June 2017 to August 2019, 628 pregnant women with high risk signaled by NIPT underwent invasive prenatal diagnosis. Amniotic fluid or cord blood samples were subjected to chromosomal karyotyping analysis or CMA. Pregnancy outcome and postnatal conditions of the fetuses were followed up. RESULTS: The positive predictive value for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidy, other rare trisomies and copy number variants (CNVs) among the 628 women were 86.4% (127/147), 41.7% (30/72), 12.9% (4/31), 43.7% (101/231), 16.5% (14/85) and 52.2% (35/67), respectively. In 218 samples with normal karyotype, 5.5% (12/218) of additional pathogenic CNVs and 2.3% (5/218) of loss of heterozygosity were detected by CMA. CONCLUSION CMA combined with karyotyping analysis can be used as first-tier test for prenatal diagnosis for women with high-risk signaled by NIPT.
Female ; Humans ; Karyotyping ; Microarray Analysis ; Pregnancy ; Prenatal Diagnosis ; Trisomy 13 Syndrome/genetics* ; Trisomy 18 Syndrome

OBJECTIVE: To analyze the Z values of true and false positive cases by non-invasive prenatal testing (NIPT) in order to improve its accuracy in clinical practice. METHODS: Results of 24 384 NIPT tests were reviewed. For cases with high risks for trisomies 21, 18 and 13, the range of Z values in true and false positive cases was analyzed and discussed. RESULTS: A total of 335 high-risk cases were identified by NIPT, among which 256 had elected prenatal diagnosis, 153 (59.77%) were verified as true positives, and 103 (40.23%) were false positives, and the area under the curve (AUC) was 0.9994. For NIPT screening, the positive predictive value (PPV) for trisomy 21 was 100% when Z>13, regardless if the pregnant woman was over 35. When 3trisomy 21 was 80% (8/10) for those>35 and about 41.6% (5/12) for those<35. For trisomy 18, the PPV was 100% when Z>13, and only 14.3% (1/7) when 3trisomy 13 was only 6.67% (1/15) when the trisomy 13 Z value was more than 20, the positive predictive value was 100% , and the trisomy 13 Z value was 3CONCLUSION NIPT is a technique similar to prenatal diagnosis and has a high positive predictive value for trisomies 18 and 21. Proper classification and division of the high-risk Z value of NIPT can further improve the positive predictive values for trisomies 21, 18 and 13 in different intervals, and is more helpful to guide clinicians in genetic counseling for high-risk pregnant women. Meanwhile, the compliance of prenatal diagnosis in high risk NIPT pregnant women with Z value between 3~13 was improved.
Female ; Pregnancy ; Humans ; Trisomy 13 Syndrome/genetics* ; Trisomy/genetics* ; Down Syndrome/genetics* ; Chromosome Disorders/genetics* ; Trisomy 18 Syndrome/diagnosis* ; Prenatal Diagnosis/methods*

OBJECTIVE: To evaluate the feasibility of non-invasive prenatal testing (NIPT) for the screening of fetal chromosome aneuploidies in twin pregnancies. METHODS: A total of 2 745 women with twin-pregnancies were subjected for NIPT screening. Chromosomal karyotyping and chromosomal microarray analysis (CMA) were carried out on amniotic fluid samples from those with a high risk for fetal chromosome aneuploidies, and the diagnosis and pregnancy outcome were followed up. The sensitivity, specificity, positive predictive value and false positive rate of the NIPT were calculated. RESULTS: Compared with other chromosomal abnormalities, NIPT had a higher efficacy for trisomy 21 and sex chromosomal aneuploidy (SCA) in twin pregnancies (with sensitivity being 100%, 100%, and specificity being 99.93%, 99.9%, respectively). It is difficult to evaluate the efficacy for trisomies 18 and 13 due to the limited data. For chromosome microdeletions and microduplications spanning 15 ~ 21 Mb, NIPT also had a certain detection rate. Compared with women with natural conception, NIPT had a higher detection rate for those with twin pregnancies by assisted reproduction (P < 0.05). CONCLUSION It is feasible to use NIPT for the detection of chromosome aneuploidies in women with twin pregnancies.
Pregnancy ; Female ; Humans ; Pregnancy, Twin ; Prenatal Diagnosis ; Down Syndrome/genetics* ; Chromosome Aberrations ; Aneuploidy ; Trisomy 18 Syndrome/genetics* ; Trisomy

OBJECTIVE: To analyze the results of prenatal diagnosis and outcome of pregnancy for women with a high risk for fetal aneuploidies. METHODS: A total of 747 cases of prenatal diagnosis by amniocentesis due to high risks by non-invasive prenatal testing (NIPT) were selected from January 2015 to March 2022 in the Drum Tower Hospital Affiliated to Nanjing University Medical School. The amniotic fluid samples were subjected to chromosomal karyotyping and/or chromosomal microarray analysis. All cases were followed up by searching the birth information or telephone calls, and the results were recorded. 2 test or F test were used for comparing the difference between the groups. RESULTS: Among the 747 pregnant women with a high risk by NIPT, 387 were true positives, and the overall positive predictive value (PPV) was 51.81%. The PPVs for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13) and sex chromosome aneuploidies (SCA) were 80.24% (199/248), 60% (48/80), 14% (7/50) and 38.97% (106/272), respectively. The PPV for T21 was significantly higher than T18 and T13 (χ² = 85.216, P < 0.0001). The PPV for other chromosomal aneuploidies and copy number variations (CNVs) were 11.11% (5/45) and 40.74% (22/52), respectively. The PPV for increased X chromosomes was significantly higher than X chromosome decreases (64.29% vs. 22.22%, χ² = 5.530, P < 0.05). The overall PPV for elder women (≥ 35 years old) was significantly higher than younger women (69.35% vs. 42.39%, χ² = 49.440, P < 0.0001). For T21 and T18, the PPV of Z ≥ 10 group was significantly higher than that for 3 ≤ Z < 5 group or 5 ≤ Z < 10 group (P < 0.05). Among 52 cases with a high risk for CNVs, the PPV for the ≤ 5 Mb group was significantly higher than the 5 Mb < CNVs < 10 Mb or > 10 Mb groups (60% vs. 30%60% vs. 23.53%, P < 0.05). Among the 387 true positive cases, 322 had opted for induced labor, 53 had delivered with no abnormal growth and development, and 12 were lost during the follow-up. CONCLUSION The PPVs for common chromosomal aneuploidies are related to the age and Z value of the pregnant women, which were higher in the elder group and higher Z value group. In addition, the PPV is associated with high risk types. The PPV for T21 was higher than T18 and T13, and that for 45,X was lower than 47,XXX, 47,XYY or 47,XXY syndrome. NIPT therefore has relatively high PPVs for the identification of chromosomal CNVs.
Female ; Pregnancy ; Humans ; Aged ; Adult ; DNA Copy Number Variations ; Prenatal Diagnosis/methods* ; Down Syndrome/genetics* ; Aneuploidy ; Trisomy 18 Syndrome/genetics* ; Trisomy 13 Syndrome/diagnosis* ; DNA ; Trisomy/genetics*

OBJECTIVE: To analyze the result of prenatal diagnosis and outcome of pregnancy for fetuses with rare autosomal trisomies (RATs) suggested by non-invasive prenatal testing (NIPT). METHODS: A total of 69 608 pregnant women who underwent NIPT at Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2020 were selected as study subjects. The result of prenatal diagnosis and outcome of pregnancy for those with a high risk for RATs were retrospectively analyzed. RESULTS: Among the 69 608 pregnant women, the positive rate of NIPT for high-risk RATs was 0.23% (161/69 608), with trisomy 7 (17.4%, 28/161) and trisomy 8 (12.4%, 20/161) being the most common, and trisomy 17 (0.6%, 1/161) being the rarest. For 98 women who had accepted invasive prenatal diagnosis, 12 fetal chromosomal abnormalities were confirmed, and in 5 cases the results were consistent with those of NIPT, which yielded a positive predictive value of 5.26%. Among the 161 women with a high risk for RATs, 153 (95%) were successfully followed up. 139 fetuses were ultimately born, with only one being clinically abnormal. CONCLUSION Most women with a high risk for RATs by NIPT have good pregnancy outcomes. Invasive prenatal diagnosis or serial ultrasonography to monitor fetal growth, instead of direct termination of pregnancy, is recommended.
Pregnancy ; Female ; Humans ; Trisomy/genetics* ; Pregnancy Outcome ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Fetus ; Trisomy 18 Syndrome/genetics* ; Aneuploidy

OBJECTIVE: To analyze the cause and pregnancy outcome for non-reportable cell-free DNA (cfDNA) results during non-invasive prenatal testing (NIPT). METHODS: cfDNA was extracted from maternal plasma from 5898 singleton pregnancies at 12 to 22 gestational weeks and underwent NIPT with strict quality control standards. For those with sub-standard results, redraw or invasive prenatal procedures were recommended. RESULTS: Among the 5898 cases, 32 have failed for the initial NIPT, including 17 cases with substandard cffDNA%, 10 cases with data fluctuation after twice library constructing and sequencing, and 5 cases with unidentifiable sex chromosome abnormalities. For these 32 cases, 2 directly underwent amniocentesis, and karyotyping analysis showed both were normal. Six of the 30 redrawn cases finally turned out to be nonreportable. The final nonreportable rate was therefore 0.1% (8/5898). Of the redrawn cases, 1 trisomy 21, 1 trisomy 18 and 1 trisomy 13 high risk-cases were identified, which were all confirmed to be false positive. Among the 6 nonreportable cases, 2 women underwent invasive prenatal testing, and 1 was found to have a normal fetal karyotype, while another was found to have an abnormal karyotype of mos45,X[32]/46,XY[18]. The other 4 nonreportable cases who did not accept invasive prenatal testing have all reported normal child development at follow-up. CONCLUSION The main reason for nonreportable NIPT results was low cffDNA%. The high success rate of the redrawn cases has effectively increased the overall NIPT success rate and reduced the number of the cases necessitating invasive prenatal diagnosis. The initially nonreportable women may consider retesting after careful counseling with informed consent.
Aneuploidy ; Child ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Noninvasive Prenatal Testing ; Pregnancy ; Prenatal Diagnosis ; Trisomy ; Trisomy 18 Syndrome/genetics*

OBJECTIVE: To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program. METHODS: A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed. RESULTS: NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035. CONCLUSION NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.
Aneuploidy ; Cost-Benefit Analysis ; Female ; Humans ; Noninvasive Prenatal Testing ; Pregnancy ; Retrospective Studies ; Trisomy 18 Syndrome/genetics*

OBJECTIVE: To assess the clinical value of non-invasive prenatal testing (NIPT) for the screening of trisomy and copy number variations (CNVs) of chromosomes 21, 18 and 13. METHODS: From January 2015 to December 2019, 40 628 pregnant women underwent NIPT testing using high-throughput sequencing and bioinformatics analysis to test the cell-free fetal DNA in maternal plasma. High-risk pregnant women underwent invasive prenatal diagnosis, while low-risk ones were followed up by telephone. RESULTS: The three most common indications included intermediate risk of serological screening, high risk of serological screening and advanced maternal age. Among all pregnant women, 257 cases were detected as trisomy 21, 18 and 13 (170, 49 and 38 cases, respectively). 227 cases chose invasive prenatal diagnosis, with respectively 122, 28 and 10 cases confirmed. The positive predictive value (PPV) was 81.33% (122/150), 65.12% (28/43), 29.41% (10/34), respectively. Two false negative cases of trisomy 18 were found during follow-up. Meanwhile, NIPT has detected 46 cases (15, 16 and 15 cases, respectively) CNVs on chromosomes 21, 18 and 13, among which 37 cases underwent invasive prenatal diagnosis. There were 5, 3 and 5 positive cases, which yielded a PPV of 41.67% (5/12), 25%(3/12) and 33.33%(5/15), respectively. Two other chromosome CNVs were accidentally discovered among the false positive samples. CONCLUSION The incidence of chromosomal abnormalities in the serological screening high-risk group was 52.02%, which was significantly higher than other groups. NIPT has a high sensitivity and specificity for the screening of trisomies 21, 18 and 13, while its accuracy for detecting CNVs of chromosomes 21, 18 and 13 needs to be improved. As a screening method, NIPT has a great clinical value, though there are still limitations of false positive and false negative results.Comprehensive pre- and post-test genetic counseling should be provided to the patients.
Aneuploidy ; Chromosome Disorders/genetics* ; Chromosomes ; DNA Copy Number Variations ; Down Syndrome/genetics* ; Female ; Humans ; Pregnancy ; Prenatal Diagnosis ; Trisomy/genetics* ; Trisomy 18 Syndrome/genetics*

OBJECTIVE: To assess the clinical efficacy and health economic value of non-invasive prenatal testing (NIPT) for the prenatal screening of common fetal chromosomal aneuploidies. METHODS: 10 612 pregnant women from October 2017 to December 2019 presented at the antenatal screening clinic of the General Hospital of Tianjin Medical University were selected as the study subjects. Results of NIPT and invasive prenatal diagnosis and follow-up outcome for the 10 612 pregnant women were retrospectively analyzed and compared. Meanwhile, NIPT data for two periods were analyzed for assessing the health economic value of NIPT as the second- or first-tier screening strategy for the prenatal diagnosis of fetal trisomies 21, 18 and 13. RESULTS: The NIPT was successful in 10 528 (99.72%) subjects, with the sensitivity for fetal trisomies 21, 18 and 13 being 100%, 92.86% and 100%, and the positive predictive value (PPV) being 89.74%, 61.90% and 44.44%, respectively. The PPV of NIPT for sex chromosome aneuploidies was 34.21%. Except for one false negative case of trisomy 18, the negative predictive value for trisomy 21, trisomy 13 and other chromosomal abnormalities were 100%. For pregnant women with high risk by serological screening, advanced maternal age or abnormal ultrasound soft markers, NIPT has yielded a significantly increased high risk ratio. There was no statistical difference in the PPV of NIPT among pregnant women from each subgroup. NIPT would have higher health economic value as a second-tier screening until 2019, while compared to 2015 ~ 2017, its incremental cost-effectiveness ratio as a first-tier screening had declined clearly. CONCLUSION The screening efficacy of NIPT for trisomies 21, 18 and 13 for a mixed population is significantly better than conventional serological screening, but it is relatively low for sex chromosomal abnormalities. NIPT can also be recommended for populations with relatively high risks along with detailed pre- and post-test genetic counselling. From the perspective of health economics, except for open neural tube defects, it is possible for NIPT to replace the conventional serological screening in the future as its cost continues to decrease.
Pregnancy ; Female ; Humans ; Trisomy/genetics* ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Down Syndrome/genetics* ; Aneuploidy ; Chromosome Aberrations ; Trisomy 18 Syndrome/genetics* ; Sex Chromosome Aberrations ; Fetus