Value Of Non-invasive Prenatal Testing Research Articles

Prevalence threshold and positive predictive value of noninvasive prenatal testing.

Noninvasive prenatal testing (NIPT) has increased the number of conditions that can be screened. However, the prevalence of conditions assessed by NIPT has remained stable. The "prevalence threshold," a novel epidemiological concept, uses a test's sensitivity and specificity to determine the prevalence below which a test's positive predictive value declines most sharply relative to disease prevalence. In this article, we calculated the prevalence threshold for common conditions assessed through NIPT and compared the value with the actual prevalence of each condition to best ascertain the reliability of NIPT results. Six databases and PubMed were searched from January 2010 to March 2023 for sensitivity and specificity parameters of common conditions tested through NIPT. Using an equation previously derived by the authors of the current paper, the prevalence threshold for each condition was calculated. The theoretical number of test iterations required to reach the prevalence threshold was also reported. None of the conditions tested through the NIPT had a prevalence rate that met or exceeded the calculated prevalence threshold. Trisomy 21 had the greatest concordance between the prevalence rate and the prevalence threshold. In contrast, Angelman, Cri-du-chat, and Prader-Willi syndromes had the most significant discordance. Apart from trisomy 21 and XXY, all remaining conditions required more than one test iteration to reach their respective prevalence threshold. We conclude that at the current prevalence levels, the positive predictive value of NIPT remains low, with the prevalence of disease levels significantly lower than the prevalence threshold for each condition tested.

Ultrasound signs of fetal chromosomal abnormalities at 11–14 weeks of pregnancy and its value in the era of modern genetic testing

A steady increase in average maternity age at the time of first childbirth lead to a higher risk of fetal chromosomal abnormalities. The Order No. 1130n of the Ministry of Health of the Russian Federation establish the screening protocol at 11–14 weeks of gestation with assessing the followed criteria of fetal chromosomal pathology: the nuchal translucency thickness, nasal bone measurement, ductus venosus pulsatility index, tricuspid regurgitation, and heart rate. The value of non-invasive prenatal testing (NIPT) in the early prenatal diagnosis of the most common chromosomal abnormalities, as the trisomies 21, 18, 13, and monosomy X is also increasing. Additionally, numerous other fetal karyotype abnormalities can also be suspected at 11–14 weeks of gestation by revealing a number of other ultrasound signs. The article presents the literature review on additional ultrasound signs of various, both more and less common, chromosomal abnormalities. Pathological signs, abnormalities of fetal anatomy and extrafetal structures in the first trimester, which could be used as additional ultrasound signs of chromosomal pathology of various organs and systems (central nervous system and head, heart and blood vessels, urinary system, abdominal organs, fetal skeleton, as well as the placenta, umbilical cord, amniotic membranes) are described in the article. Despite the use of NIPT, including its extended panels, there remains a need to use ultrasound to detect the signs of rarer, but no less significant chromosomal pathologies, such as triploidies, mosaic trisomies, rare autosomal trisomies, duplications, and deletions.

Value of non-invasive prenatal testing for rare autosomal trisomies in fetuses

To evaluate the value of non-invasive prenatal testing(NIPT)for detecting rare autosomal trisomies in fetuses. We retrospectively analyzed the data of cases with rare autosomal trisomies detected by NIPT in our hospital from January, 2019 to April, 2023.Invasive prenatal diagnostic tests including chromosome karyotype analysis, chromosome microarray analysis, copy number variation sequencing, and fluorescence in situ hybridization were performed in all the cases after clinical counseling, and their test results and pregnancy outcomes were analyzed. Among 25 282 women receiving NIPT, 56(0.22%)were found to have high risks for rare autosomal trisomies in circulating plasma DNA.Trisomy 7 was the most frequently detected trisomy, accounting for 45% of the total cases(25/56), while trisomies 1, 4, 17, and 19 were not detected.Among the 46 cases with genetic results of the fetuses, 10 were identified to have true fetal mosaicism.The overall positive predictive value of NIPT was 22%(10/46)for rare autosomal trisomies, and 10% for trisomy 7(2/20).Of the 52 cases followed up for pregnancy outcomes, 33(63%)cases without fetal mosaicism resulted in normal live births, while 10 had unfavorable outcomes including fetal growth restriction, preterm birth, and maternal complications, and among them fetal growth restriction was the most typical and the earliest condition observed in these cases.Among the 22 followed up cases of non-true mosaicism for trisomy 7, 82% resulted in normal live births. NIPT increases the detection rate of true fetal mosaicism but with a low positive predictive value.Most of the cases with non-true mosaicism, particularly trisomy 7, can have favorable outcomes.NIPT can also be useful in identifying causes of fetal growth restriction in the second and third trimesters when invasive prenatal testing does not reveal abnormalities.

Effect of maternal age on foetal chromosomal defects: an investigation based on non-invasive prenatal testing

Background This study aimed to evaluate the value of non-invasive prenatal testing (NIPT) in the prenatal screening of foetal aneuploidy-associated diseases at different gestational ages. Methods Briefly, cell-free foetal DNAs were extracted from plasma first, followed by DNA sequencing and bioinformatics analyses for chromosome aneuploidy (T21, T18, and T13), sex chromosome aneuploidy (SCA), and microdeletion/microduplication. Subsequently, the positive results were subject to karyotype analyses. Results The pregnant women included in this study were divided into six groups, and the results, such as chromosome diagnoses, and clinical phenotypes, were collected for data analyses. According to the results of the data analysis, the positivity rates of foetal chromosomal abnormalities in pregnant women under 20, 20–24, 25–29, 30–34, 35–39, and >40 years old were 0%, 0.17%, 0.25%, 0.27%, 0.60%, and 1.66%, respectively. The positive predictive value (PPV) in the 20–24 years group was 41.67%, that in the 25–29 years group was 62.5%, that in the 30–34 years group was 66.67%, that in the 35–39 years group was 90.74%, and that in the >40 years group was 90.32%. Conclusion Overall, NIPT detection in elderly pregnant women has excellent clinical application value in reducing the incidence of either birth defects or abortion caused by invasive chromosome examination.

Retracted: Study on the Clinical Value of Noninvasive Prenatal Testing in Screening the Chromosomal Abnormalities of the Fetus in the Elderly Pregnant Women

Retracted: Study on the Clinical Value of Noninvasive Prenatal Testing in Screening the Chromosomal Abnormalities of the Fetus in the Elderly Pregnant Women

The value of non-invasive prenatal testing for the identification of numerical and structural chromosomal abnormalities and copy number variations in the fetuses

To assess the value of non-invasive prenatal testing (NIPT) for the identification of numerical and structural chromosomal abnormalities and copy number variations (CNVs) in fetuses. 46 197 pregnant women undergoing NIPT at the Prenatal Diagnosis Center of Chenzhou First People's Hospital from January 2018 to December 2021 were selected as the study subjects. Positive cases were subjected to chromosomal karyotyping and copy number variation sequencing (CNV-seq) following amniocentesis. Nearly 50% of common chromosomal aneuploidies were found in the elder pregnant women. Among these, sex chromosome aneuploidies were mainly found in pregnant women with advanced age as well as borderline risks by serological screening. Rare autosomal aneuploidies and CNVs were mainly found in those with borderline or high risks by serological screening. The positive predictive values (PPV) for fetal chromosomal abnormalities indicated by NIPT were as follows: T21 (92.37%, 109/118), T18 (53.85%, 14/26), sex chromosome aneuploidies (45.04%, 59/131), T13 (34.62%, 9/26), CNVs (29.17%, 14/48), and rare autosomal aneuploidies (2.60%, 2/77). NIPT has a high detection rate for T21, T18, T13 and sex chromosome aneuploidies. It can also detect rare autosomal aneuploidies and CNVs, including some rare structural abnormalities, though verification is required by analyzing amniotic fluid samples.

Retrospective analysis of cell-free fetal DNA prenatal testing of maternal peripheral blood

To assess the value of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, chromosomal microdeletions and microduplications using cell-free fetal DNA from peripheral blood samples of pregnant women. A total of 15 237 pregnant women who had undergone NIPT testing at the Maternity and Child Health Care Hospital of Zaozhuang from February 2015 to December 2021 were enrolled in this study. For those with a high risk by NIPT, amniotic fluid samples were collected for G-banding chromosomal karyotyping analysis and chromosomal microarray analysis to verify the consistency of NIPT with results of prenatal diagnosis. All of the women were followed up by telephone for pregnancy outcomes. Among the 15 237 pregnant women, 266 (1.75%) were detected with a high risk for fetal chromosomal abnormality were detected. Among these, 79 (29.7%) were at a high risk for T21, 26 (9.77%) were at a high risk for T18, 9 (3.38%) were at a high risk for T13, 74 (27.82%) were at a high risk for sex chromosome aneuploidies, 12 (4.51%) were at a high risk for other autosomal aneuploidies, and 66 (24.81%) were at a high risk for chromosomal microdeletions or microduplications. 217 women had accepted invasive prenatal diagnosis and respectively 50, 13, 1, 25, 1 and 18 were confirmed with T21, T18, T13, sex chromosome aneuploidies, autosomal aneuploidies and microdeletions/microduplications, and the positive predictive values were 75.76%, 68.42%, 11.11%, 40.32%, 10% and 35.29%, respectively. For 13 042 women (85.59%), the outcome of pregnancy were successfully followed up. During the follow-up, one false negative case of T21 was discovered. No false positive cases for T13 and T18 were found. NIPT has a sound performance for screening T13, T18 and T21, and is also valuable for screening other autosomal aneuploidies, sex chromosome aneuploidies and chromosomal microdeletions/microduplications.

Prenatal diagnosis of two fetuses with Xp22.31 microdeletion syndrome indicated by non-invasive prenatal testing

To assess the value of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal microdeletion/microduplication syndromes by carrying out prenatal diagnoses for two fetuses with Xp22.31 microdeletion indicated by NIPT. Two pregnant women suspected for fetal Xp22.31 microdeletion syndrome who presented at Zaozhuang Maternal and Child Health Care Hospital on December 5, 2017 and October 15, 2020 were selected as the study subjects. Clinical data of the two women were collected, and peripheral venous blood samples were collected for NIPT testing. Amniotic fluid samples were taken for G-banding chromosomal karyotyping analysis and copy number variation sequencing (CNV-seq) for fetus 1, while G-banding chromosomal karyotyping and single nucleotide polymorphism microarray analysis (SNP array) were carried out for fetus 2. Peripheral venous blood samples of couple 1 were collected for CNV-seq to verify the origin of copy number variation . NIPT indicated that fetus 1 had harbored a 1.3 Mb deletion in the Xp22.31 region, while G-banding chromosomal karyotyping had found no abnormality. CNV-seq analysis verified the fetus to be seg[GRCh37]del(X)(p22.31)chrX:g.6800001_7940000del, with a 1.14 Mb deletion at Xp22.31, which was derived from its mother. NIPT indicated that fetus 2 had harbored a 1.54 Mb deletion in the Xp22.31 region, while G-banding chromosomal karyotyping had found no abnormality. SNP array analysis indicated arr[GRCh37]Xp22.31(6458940_8003247)×0, with a 1.54 Mb deletion in Xp22.31 region. NIPT not only has a good performance for detecting fetal trisomies 21, 18 and 13, but also has the potential for detecting chromosomal microdeletion/microduplications. For high risk fetuses indicated by NIPT, prenatal diagnosis needs to be carry out to verify the chromosomal abnormalities.

Analysis of the results of non-invasive prenatal testing (NIPT) in 545 pregnant women in advanced maternal age.

This research aimed to explore the value of non-invasive prenatal testing (NIPT) as a prenatal screening method for common aneuploidy in pregnant women in advanced maternal age. A retrospective analysis was conducted on a cohort of 545 mothers with singleton pregnancy who were of advanced age and underwent NIPT testing voluntarily at the Second Affiliated Hospital of Guangxi Medical University between November 2020 and February 2023. In cases where NIPT testing suggested chromosomal abnormalities, amniocentesis was conducted, karyotype analysis or gene copy number variation (CNV) testing was performed, and the pregnancy outcome was tracked. Among 545 pregnant women in advanced maternal age, 11 cases had high risk of NIPT, and the detection rate was 2.02%. Among 11 pregnant women deemed to be at high risk for NIPT, 10 cases underwent amniotic fluid puncture, and one case refused amniocentesis despite a suggestive chromosomal abnormality in NIPT. The overall rate of amniocentesis was 1.83%. Among 11 pregnant women deemed to be at high risk for NIPT, the results suggested that 5 of them had trisomy 21, 1 had trisomy 18, 2 had sex chromosome abnormalities (specifically, 47, XYY), and 3 had other autosomal abnormalities. The positive predictive values of NIPT were 100.00% for the cases of trisomy 21 and trisomy 18, while the values were 0.00% for the cases of sex chromosome abnormalities and other autosomal abnormalities, respectively. After the follow-up, each of the 6 cases that were diagnosed with definite chromosomal abnormalities during prenatal screening opted to induce labor and terminate the pregnancy, including 5 cases that exhibited a high risk of trisomy 21 (47, XN,+21) and 1 case that showed a high risk of trisomy 18 (47, XN,+18). One instance of NIPT indicated a potential abnormality in the sex chromosomes, the individual declined to undergo amniocentesis. Another instance of NIPT suggested a sex chromosome abnormality, amniocentesis revealed a deletion of 0.72 Mb in the 4q22.1 region. They all had normal pregnancies and normal newborns. The remaining three cases had normal prenatal diagnoses (46, XN) and experienced normal pregnancies with healthy neonatal outcomes. NIPT has demonstrated its efficacy as a screening tool in the face of increasing maternal age. As a result, it can substantially decrease the requirement for invasive prenatal diagnosis. Nonetheless, there are instances of erroneous positive outcomes in NIPT testing, and therefore, interventional prenatal diagnosis remains necessary for individuals with high-risk screening outcomes to prevent false positives or unwarranted labor induction.

Value of noninvasive prenatal testing in the detection of rare fetal autosomal abnormalities

ObjectivesTo evaluate the value of noninvasive prenatal testing (NIPT) in the screening of rare autosomal abnormalities and provide further support for the clinical application of NIPT. Study designA total of 81,518 pregnant women who underwent NIPT at the Anhui Maternal and Child Health Hospital between May 2018 and March 2022 were selected. The high-risk samples were analyzed using amniotic fluid karyotype and chromosome microarray analysis (CMA), and the pregnancy outcomes were followed up. ResultsNIPT detected 292 cases (0.36%) with rare autosomal abnormalities among the 81,518 cases sampled. Of these, 140 (0.17%) showed rare autosomal trisomies (RATs), and 102 of these patients agreed to undergo invasive testing. Five cases were true positives, with a positive predictive value (PPV) of 4.90%. Copy number variants (CNV) were detected in 152 samples of the total cases (0.19%), and 95 of the patients involved agreed to the use of CMA. Twenty-nine of these cases were confirmed to be true positive, with a PPV of 30.53%. Detailed follow-up information was obtained in 81 cases from 97 patients with false-positive results for RATs. Thirty-seven of these cases (45.68%) had adverse perinatal outcomes, with a higher incidence of small for gestational age (SGA), intrauterine growth retardation (IUGR), and preterm birth (PTB). ConclusionsNIPT is not recommended for screening for RATs. However, considering that positive results are associated with an increased risk of IUGR and PTB, additional fetal ultrasound examination should be performed to monitor fetal growth. In addition, NIPT has a reference value in screening for CNVs, especially pathogenic CNVs, but a comprehensive analysis of prenatal diagnosis combined with ultrasound and family history is still needed.

Clinical application and evaluation of health economics for non-invasive prenatal testing of fetuses in Tianjin

To assess the clinical efficacy and health economic value of non-invasive prenatal testing (NIPT) for the prenatal screening of common fetal chromosomal aneuploidies. 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. 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. 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.

Značaj NIPT U kombinaciji sa serumom bez DNK ćelija, estriolom, AFP i nivoom b-HCG U prepoznavanju trizomije 21 i 18 u drugom trimestru

Background: This study aimed to evaluate the clinical application value of noninvasive prenatal testing from DNA (NIPT) and serum screening for screening in detecting fetal trisomy 21 and 18. Methods: As a retrospective analysis, we collected data from 1383 women (singleton pregnancy) who underwent serum screening and noninvasive prenatal testing from DNA (NIPT) in our department from May 2015 to September 2017 and calculated the diagnostic value of the two methods. Results: In 1383 cases, the sensitivity of serum screening to trisomy 21 and 18 was 76.9%, specificity 74.7%, PPV 2.9%, NPV 99.7%, and AUC 0.758 (95% CI: 0.625-0.891). The sensitivity of noninvasive prenatal testing from DNA (NIPT) to trisomy 21 and 18 was 100%, specificity 99.8%, PPV 81%, NPV 100%, and AUC 0.999 (95% CI: 0.000-1.000). Conclusion: Serum screening can detect high-risk pregnant women in time, but the incidence of false positives and negatives is high; the accuracy of noninvasive prenatal testing from DNA (NIPT) is high, which can effectively reduce the rate of defective babies.

Clinical evaluation of true and false positive Z values among high-risk cases screened by non-invasive prenatal testing

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. 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. 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 3<Z<13, the PPV for trisomy 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 3<Z<13. NIPT showed that the positive predictive value of trisomy 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 3<Z<20. 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.

Study on the Clinical Value of Noninvasive Prenatal Testing in Screening the Chromosomal Abnormalities of the Fetus in the Elderly Pregnant Women.

Introduction To explore the clinical value of noninvasive prenatal testing (NIPT) in screening the chromosomal abnormalities of the fetus in the elderly pregnant women. Materials and Methods Between January 2020 and December 2021, 1949 elderly pregnant women underwent NIPT in our hospital. At the same time, 236 elderly pregnant women received invasive prenatal diagnosis, and the pregnancy outcomes were followed-up. Results When NIPT was used for prenatal screening of fetal chromosomal aneuploidy, its diagnostic coincidence rate for trisomy 21 was the highest, with a coincidence rate of 90.00%, and the diagnostic coincidence rate for other chromosomal abnormalities was the lowest, only 22.22%. The sensitivity, specificity, positive predictive rate, and negative predictive rate for T21 by NIPT were 100%, 99.97%, 94.28%, and 100%; for T18 were 100%, 99.92%, 72.22%, and 100%, respectively; and for T13 were 100%, 99.95%, 50%, and 100%, respectively. Patients with high risks according to NIPT results further received invasive prenatal diagnosis, and 18 cases were excluded from the follow-up. For the remaining 1933 cases in the NIPT group, there was an incidence of 2.28% of adverse pregnancy outcomes. For the remaining 234 cases in the Amniocentesis group, there was an incidence of 1.28% of adverse pregnancy outcomes. There was no significant difference between the two groups (P > 0.05). The diagnostic rate of fetal chromosomal abnormalities in pregnant women under 40 years old was about 0.39-0.79%; however, the risk for people over 40 is relatively high at 1.32-4.44%. Conclusion The noninvasive prenatal screening of fetal DNA in the second trimester of pregnancy for elderly pregnant women has high application value in the prediction of pregnancy outcome. The high risk of pregnancy can be determined by detecting trisomy 21, 18, and 13 syndromes, and the probability of adverse pregnancy outcome increases.

Analysis of the factors influencing positive predictive value of noninvasive prenatal testing for chromosome aneuploidies

Objective: To investigate the influence of Z-score and different risk factors on positive predictive value (PPV) of noninvasive prenatal testing (NIPT) for chromosome aneuploidies. Methods: A total of 81 838 NIPT samples from January 1, 2016 to May 31, 2021 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Invasive prenatal diagnosis was applied to verify the diagnosis of NIPT-positive results and the corresponding PPV was calculated. The PPV of the samples with different Z-score were compared. The women were divided into high-risk group and non-high-risk group: high-risk group (n=39 114) included those with ultrasound soft index abnormalities, advanced maternal age or high risk for maternal serum screening, while non-high-risk group (n=42 724) included those with intermediate risk for maternal serum screening or no indications. The differences of the PPV between these two groups were compared. Finally, the comprehensive influence of Z-score and different risk factors on PPV were analyzed. Results: A total of 471 high-risk cases were detected by NIPT results, including 362 cases of trisomy 21, 77 cases of trisomy 18 and 32 cases of trisomy 13. For trisomy 21, trisomy 18 and trisomy 13, there were 226 cases, 46 cases and 6 cases which were confirmed via invasive prenatal diagnosis respectively. The corresponding PPV were 79.3% (226/285), 82.1% (46/56) and 27.3% (6/22), respectively. PPV of trisomy 21 and trisomy 18 were positively correlated with the corresponding Z-score (r=0.92, 0.62, all P<0.05), while trisomy 13 could not be analyzed due to the small sample size. The PPV of high-risk group was 85.2% (207/243), which was higher than that of the non-high-risk group with PPV of 59.2%(71/120, χ2=30.30, P<0.01). When the Z-score was between 3-<4 and 4-<5, the PPV of the high-risk group were 46.2%(12/26)and 62.5%(15/24) respectively, which were higher than those of the non-high-risk group [16.0%(4/25) and 14.3%(3/21), χ2=4.10, 8.90, all P<0.05]. With the increase of Z-score, there was no significant difference in PPV between the two groups (all P>0.05). Conclusions: The PPV of trisomy 21 and trisomy 18 are positively correlated with Z-score. The PPV of high-risk group is higher than that of non-high-risk group. The combination of Z-score and other risk factors may provide more accurate genetic counseling for those with NIPT positive results.

Practice of clinical application of noninvasive prenatal testing based on cell-free fetal DNA

To assess the application value of noninvasive prenatal testing (NIPT) based on cell-free fetal DNA. The results of 2777 cases of basic and extended NIPT were retrospectively analyzed. The clinical data and outcome of pregnancy were analyzed, in addition with the diagnosis rate and testing efficiency. Among the 2777 pregnant women, 1192 (42.9%) had accepted basic NIPT and 1585 (57.1%) accepted extended NIPT. With a failure rate of 0.1%, 8 and 6 cases were reported respectively as high-risk pregnancies for trisomy 21 and sex chromosomal abnormalities. Other genetic abnormalities were detected in 32 cases. The positive predictive value for trisomy 21 was 85.7%, and one case of 47,XXX was diagnosed among 3 women with high risks for sex chromosomal abnormalities. For those with a high risk for other genetic abnormalities, pregnant diagnosis rates of basic and extended NIPT were 71.4% (5/7) and 68.2% (15/22), respectively. Seven copy number variations (CNVs) were confirmed, including one pathogenic CNV, one likely pathogenic CNV and 5 variants of unknown significance. Among 6 cases with high-risk of maternal CNVs, 5 fetuses and the mothers were confirmed to be carriers. No CNV was detected in the remainder fetus by chromosomal microarray analysis, while its mother was a carrier of the corresponding CNV. NIPT has shown a relatively high positive predictive value for the screening of trisomy 21 and maternal CNVs but with a limited efficiency for the discovery of fetal CNVs. For other genetic abnormalities signaled by NIPT, informed choice by the pregnant women during pre-testing consultation is recommended. Invasive prenatal diagnosis should be considered in the combination of NIPT reports and fetal ultrasound, while the residual risks should be fully informed.

The role of first-trimester ultrasound screening for women with positive noninvasive prenatal testing results.

This study aimed to assess the utility of ultrasound screening for pregnancies with positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. We performed a retrospective analysis of positive noninvasive prenatal testing results and first-trimester ultrasound screening at our department between 2013 and 2019. Invasive genetic testing was performed if the patient had positive noninvasive prenatal testing results. Fetal ultrasound and cytogenetic data were collected. Noninvasive prenatal testing was performed in the women for advanced maternal age, nuchal translucency thickness, or history of abnormality in the previous child or relative. Forty-one pregnant women had positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. Twenty-three women had positive results for trisomy 21, 13 had positive results for trisomy 18, and 5 had positive results for trisomy 13 at 11 to 14 weeks of gestation. The positive predictive value of noninvasive prenatal testing was 100% for trisomy 21, 84.6% for trisomy 18, and 100% for trisomy 13. The positive predictive value of positive noninvasive prenatal testing results and fetal morphological abnormalities was 100% for trisomy 21, trisomy 18, and trisomy 13. Combining an ultrasound examination with noninvasive prenatal testing resulted in a higher positive predictive value for trisomy 18. Normal ultrasound examination results can help alleviate stress caused by false-positive noninvasive prenatal testing results. In contrast, the positive predictive value and negative predictive value for trisomy 21 were not altered by adding an ultrasound examination to noninvasive prenatal testing.

Expanding the application of non-invasive prenatal testing in the detection of foetal chromosomal copy number variations

PurposeThe aim of this study was to assess the detection efficiency and clinical application value of non-invasive prenatal testing (NIPT) for foetal copy number variants (CNVs) in clinical samples from 39,002 prospective cases.MethodsA total of 39,002 pregnant women who received NIPT by next-generation sequencing (NGS) with a sequencing depth of 6 M reads in our centre from January 2018 to April 2020 were enrolled. Chromosomal microarray analysis (CMA) was further used to diagnose suspected chromosomal aneuploidies and chromosomal microdeletion/microduplication for consistency assessment.ResultsA total of 473 pregnancies (1.213%) were positive for clinically significant foetal chromosome abnormalities by NIPT. This group comprised 99 trisomy 21 (T21, 0.254%), 30 trisomy 18 (T18, 0.077%), 25 trisomy 13 (T13, 0.064%), 155 sex chromosome aneuploidy (SCA, 0.398%), 69 rare trisomy (0.177%), and 95 microdeletion/microduplication syndrome (MMS, 0.244%) cases. Based on follow-up tests, the positive predictive values (PPVs) for the T21, T18, T13, SCA, rare trisomy, and MMS cases were calculated to be 88.89%, 53.33%, 20.00%, 40.22%, 4.88%, and 49.02%, respectively. In addition, the PPVs of CNVs of < 5 Mb, 5–10 Mb, and > 10 Mb were 54.55%, 38.46%, and 40.00%, respectively. Among the 95 cases with suspected CNVs, 25 were diagnosed as true positive and 26 cases as false positive; follow-up prenatal diagnosis by CMA was not performed for 44 cases. Moreover, among the 25 true positive cases, 10 were pathogenic, 3 were likely pathogenic, and 12 were of uncertain significance.ConclusionNIPT is not only suitable for screening T21, T18, T13, and SCA but also has potential significance for CNV detection. As combined with ultrasound, extended NIPT is effective for screening MMS. However, NIPT should not be recommended for whole-chromosome aneuploidy screening.

Analysis of the results of chromosomal trisomies 21, 18 and 13 screening among 40 628 women by non-invasive prenatal testing

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. 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. 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. 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.

Performance of non-invasive prenatal testing for foetal chromosomal abnormalities in 1048 twin pregnancies

ObjectiveTo investigate the clinical value of non-invasive prenatal testing (NIPT) to screen for chromosomal abnormalities in twin pregnancies and to provide further data on NIPT manifestations in twin pregnancies.Materials and methodsIn a 4-year period, 1048 women with twin pregnancies were voluntarily prospectively tested by NIPT to screen for chromosomal abnormalities by sequencing cell-free foetal DNA (cffDNA) in maternal plasma. Positive NIPT results were confirmed by karyotyping, while negative results were followed up 42 days after delivery.ResultsThirteen women had positive NIPT results as follows: 2 cases of trisomy 21 (T21), 1 of trisomy 18 (T18), 7 of sex chromosome aneuploidy (SCA), 1 of microdeletion, and 2 of microduplication. Of these 13 cases, 2 were true-positive cases confirmed by foetal karyotype analysis, namely, 1 case of T21 and 1 of 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). There were no false-negative case via our follow-up results.ConclusionSafe 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.