Clinical evaluation of non-invasive prenatal screening in 32,394 pregnancies from Changzhi Maternal and Child Health Care Hospital of Shanxi China

Non-invasive prenatal screening (NIPS)was performed in 32,394 pregnancies, out of which results were available in 32,361 (99.9%) of them.Among the 32,361confirmed samples, 164 cases had positive results and 32197 cases had negative results. Of these positive cases, 116 cases were trisomy 21, 34 cases were trisomy 18 and 14 cases were trisomy 13. No false negative results were found in this cohort. The overall sensitivity and specificity were 100% and 99.91%, respectively. There was no significant difference in test performance between the 7,316 high-risk and 25,045 low-risk pregnancies，(sensitivity, 100% vs 100% (P >0.05); specificity, 99.96% vs 99.95% (P > 0.05)). Factors contributing to false-positive results included fetal CNVs, fetal mosaicism and typically producing Z scores between 3 and 4. Moreover, we analyze NIPT whole-genome sequencing to investigate the Single Nucleotide Polymorphisms (SNPs) associations with drug response or risk of disease. As compare to the 1000g East Asian genome data, the results reveal a significant difference in 7,285,418 SNPs variants of Shanxi pregnant women including 19，293 clinvar recorded variants and 7,266,125 non- clinvar recorded. Our findings showed that NIPS was an effective assay that may be applied as routine screening for fetal trisomies in the prenatal setting. In addition, this study also provides an accurate assessment of significant differencein 7,285,418 SNPs variants in Shanxi pregnant women that were previously unavailable to clinicians in Shanxi population.

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Analyzing false‐negative results detected in low‐risk non‐invasive prenatal screening cases

Molecular Genetics & Genomic Medicine ◽

10.1002/mgg3.1185 ◽

2020 ◽

Vol 8 (4) ◽

Author(s):

Ying Lin ◽

Dong Liang ◽

Yan Wang ◽

Hang Li ◽

An Liu ◽

...

Keyword(s):

Prenatal Screening ◽

False Negative ◽

Low Risk ◽

Non Invasive ◽

Negative Results ◽

False Negative Results

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Cell-free DNA screening for aneuploidies in 7113 pregnancies: single Italian centre study

Genetics Research ◽

10.1017/s001667232000004x ◽

2020 ◽

Vol 102 ◽

Cited By ~ 1

Author(s):

Alvaro Mesoraca ◽

Katia Margiotti ◽

Claudio Dello Russo ◽

Anthony Cesta ◽

Antonella Cima ◽

...

Keyword(s):

Sex Chromosome ◽

Clinical Performance ◽

False Negative ◽

Prenatal Testing ◽

High Sensitivity ◽

Trisomy 13 ◽

Sequencing Platform ◽

Non Invasive ◽

Negative Results ◽

False Negative Results

Abstract Introduction Non-invasive prenatal testing (NIPT) using cell-free foetal DNA has been widely accepted in recent years for detecting common foetal chromosome aneuploidies, such as trisomies 13, 18 and 21, and sex chromosome aneuploidies. In this study, the practical clinical performance of our foetal DNA testing was evaluated for analysing all chromosome aberrations among 7113 pregnancies in Italy. Methods This study was a retrospective analysis of collected NIPT data from the Ion S5 next-generation sequencing platform obtained from Altamedica Medical Centre in Rome, Italy. Results In this study, NIPT showed 100% sensitivity and 99.9% specificity for trisomies 13, 18 and 21. Out of the 7113 samples analysed, 74 cases (1%) were positive by NIPT testing; foetal karyotyping and follow-up results validated 2 trisomy 13 cases, 5 trisomy 18 cases, 58 trisomy 21 cases and 10 sex chromosome aneuploidy cases. There were no false-negative results. Conclusion In our hands, NIPT had high sensitivity and specificity for common chromosomal aneuploidies such as trisomies 13, 18 and 21.

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Prenatal diagnosis of 4953 pregnant women with indications for genetic amniocentesis in Northeast China

Molecular Cytogenetics ◽

10.1186/s13039-019-0457-x ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 2

Author(s):

Rulin Dai ◽

Yang Yu ◽

Qi Xi ◽

Xiaonan Hu ◽

Haibo Zhu ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Pregnant Women ◽

Northeast China ◽

Prenatal Screening ◽

Chromosomal Abnormalities ◽

False Negative ◽

Screening Methods ◽

Serological Screening ◽

Diagnostic Center ◽

Positive Results

Abstract Background Several different technologies are used for prenatal screening procedures and genetic diagnostic technologies. We aimed to investigate the rates of chromosomal abnormalities in cases with different abnormal prenatal indications and to determine the relationships between fetal chromosomal abnormalities and indicators of prenatal abnormalities in Northeast China. Methods We evaluated 4953 16- to 23-week singleton gestation cases using amniocentesis and a total of 3583 participants received serological screening. Fetal chromosomal analyses were performed for all samples using fluorescence in situ hybridization and karyotyping. Results Among these samples, 204 (4.12%) had fetal chromosomal abnormalities. A total of 3583 participants received serological screening, among whom 102 (2.85%) exhibited positive results. A total of 309 participants had ultrasonography; 42 (13.6%) of these had abnormalities. Among 97 participants who had non-invasive prenatal testing (NIPT), 59 (61%) had positive results. Among 1265 participants with advanced maternal age, 78 (6.2%) had abnormal results. Conclusion The serological screening and NIPT that were included in the prenatal screening methods all had false positive and false negative rates. Although they are both prenatal screening techniques, maternal serum screening cannot be replaced by NIPT. The pregnancy women should accept NIPT in a qualified prenatal diagnostic center. We recommend that pregnant women at high or critical risk undergoing prenatal screening should confirm the fetal karyotype through amniocentesis. Moreover, if women receive a positive result via NIPT, they should not have a pregnancy termination without undergoing further prenatal diagnosis.

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Analysis of Prenatal Diagnosis Results and Pregnancy Outcome of Non-invasive Prenatal Screening High-risk Fetuses

10.21203/rs.3.rs-74234/v1 ◽

2020 ◽

Author(s):

Yan Luo ◽

Yanmei Sun ◽

Haishen Tian ◽

Hezhen Lu ◽

Lishuang Ma ◽

...

Keyword(s):

Prenatal Diagnosis ◽

High Risk ◽

Pregnant Women ◽

Clinical Significance ◽

Prenatal Screening ◽

Trisomy 13 ◽

Chromosomal Microarray Analysis ◽

Non Invasive ◽

Chromosomal Karyotype

Abstract BackgroundWith the development of whole-genome sequencing, small chromosomal deletions and duplications could be found by NIPT. This study is to evaluate the clinical significance of fetal chromosomal karyotype analysis and chromosomal microarray analysis (CMA) to clarify the clinical significance of 528 cases of high-throughput sequencing noninvasive prenatal screening suggesting high-risk cases. MethodsNon-invasive prenatal screening showed that the fetus 21, 18, 13, sex chromosomes, and other chromosomes are at high risk of aneuploidy and fetal chromosome copy number variations (CNVs) are at high risk, requiring prenatal diagnosis Pregnant women are the research objects. After obtaining informed consent, fetal cells were obtained by amniocentesis or umbilical vein puncture for chromosomal karyotype and CMA analysis. All cases of childbirth were followed up by telephone over a period of 1 year.Results Among 528 fetuses, 447 were at high risk of aneuploidy. The positive predictive value (PPV) for trisomy 21(T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies (SCAs), and other chromosome aneuploidy was 85.24%, 51.52%, 12.5%, 50.82%, and 5.88% respectively. Another 81 cases of non-invasive prenatal screening suggest CNVs High risk. The PPV for CNVs was 34.57% .Among them, CNVs has a clear pathogenic significance can reach 24.69% . Follow-up of childbirth cases: Of the 62 pregnant women diagnosed with fetal SCA, 13 chose to continue their pregnancy, and the overall continued pregnancy rate was 20.97% (13/62); CNVs has no clear significance/no disease reported in 8 cases, 1 case After being lost to follow-up, all 7 cases chose to continue their pregnancy. One of the children was not informed about the specific situation; one girl had six fingers on both hands, and the rest had no abnormal growth; the remaining five children developed normally. ConclusionThis study has obtained relatively reliable PPV data for NIPT screening for chromosomal aneuploidy, which provides a reliable basis for clinical genetic counseling and treatment; it is recommended to perform prenatal diagnosis and perform chromosomal nucleus when non-invasive and high-risk prompts suspicious chromosomal abnormalities (over/under/microdeletion/microduplication). Type and CMA inspection, so that the inspection is more comprehensive and not easy to miss the diagnosis.

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Critical Evaluation of Impedance Phlebography for the Diagnosis of Deep Vein Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649161 ◽

1974 ◽

Vol 31 (02) ◽

pp. 273-278

Author(s):

Kenneth K Wu ◽

John C Hoak ◽

Robert W Barnes ◽

Stuart L Frankel

Keyword(s):

Deep Vein Thrombosis ◽

False Positive ◽

False Negative ◽

Critical Evaluation ◽

Original Method ◽

Vein Thrombosis ◽

Negative Results ◽

False Negative Results ◽

Deep Vein ◽

Positive Results

SummaryIn order to evaluate its daily variability and reliability, impedance phlebography was performed daily or on alternate days on 61 patients with deep vein thrombosis, of whom 47 also had 125I-fibrinogen uptake tests and 22 had radiographic venography. The results showed that impedance phlebography was highly variable and poorly reliable. False positive results were noted in 8 limbs (18%) and false negative results in 3 limbs (7%). Despite its being simple, rapid and noninvasive, its clinical usefulness is doubtful when performed according to the original method.

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Diagnostic Performance of Ankle-Brachial Pressure Index in Lower Extremity Arterial Disease

The Surgery Journal ◽

10.1055/s-0041-1731444 ◽

2021 ◽

Vol 07 (03) ◽

pp. e132-e137

Author(s):

Mohammed Alagha ◽

Thomas M. Aherne ◽

Ahmed Hassanin ◽

Adeel S. Zafar ◽

Doireann P. Joyce ◽

...

Keyword(s):

Lower Extremity ◽

Sensitivity And Specificity ◽

False Negative ◽

Arterial Disease ◽

Initial Assessment ◽

Reference Standard ◽

Lower Extremity Arterial Disease ◽

Negative Results ◽

Positive Results ◽

Arterial Imaging

Abstract Introduction Ankle-brachial pressure indices (ABIs) continue to form the basis of diagnostics for lower extremity arterial disease (LEAD). However, there remains a paucity of data to support its accuracy. This study aims to evaluate its diagnostic sensitivity and specificity using established arterial-imaging modalities as a benchmark. Methods In this retrospective study, a regional, prospectively maintained, vascular laboratory database was interrogated to identify referred patients with arterial disease who underwent concomitant assessment with ABI and lower limb arterial duplex ultrasound (DUS). Duplex acted as the reference standard. Those who had peripheral computed tomography angiogram (CTA) within 3 months of initial assessment were included in a subgroup analysis to correlate ABI with CTA. The primary end point was the sensitivity and specificity of ABI compared with DUS as the reference standard. Results Concomitant assessment was performed in 438 limbs (250 patients) over a 27-month period. The ABI was normal (0.9 to 1.4) in 196 limbs (44.9%) and abnormal in the remaining 241 limbs (55.1%). False-positive results occurred in 83 out of 241 limbs (34.4%), and false-negative results occurred in 54 limbs out of 196 (27.5%). True-positive results were 158 out of 241 limbs (65.6%), whereas true-negative results were 142 out of 196 limbs (72.4%). ABI using DUS as a benchmark identified a sensitivity for peripheral artery disease of 72.3% and a specificity of 69.3%. Concomitant CTA imaging was available in 200 limbs. The sensitivity and specificity of ABI correlated with CTA were 65.5 and 68.8%, respectively. Conclusion ABIs have a moderate predictive value in the diagnosis of LEAD. Normal range outcomes cannot be taken to infer the absence of LEAD and, as such, further arterial imaging in the form of DUS or angiography should be strongly considered in those with suspected underlying disease requiring intervention. Further noninvasive tests such as exercise studies or pulse volume waveforms should be considered, if diagnostic uncertainty exists, in those requiring nonoperative intervention and risk factor control.

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Efficiency of non-invasive prenatal screening in pregnant women at advanced maternal age

BMC Pregnancy and Childbirth ◽

10.1186/s12884-021-03570-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hui Zhu ◽

Xiaoxiao Jin ◽

Yuqing Xu ◽

Weihua Zhang ◽

Xiaodan Liu ◽

...

Keyword(s):

High Risk ◽

Pregnant Women ◽

Predictive Value ◽

Trisomy 21 ◽

Maternal Age ◽

Prenatal Screening ◽

Advanced Maternal Age ◽

Youden Index ◽

Non Invasive ◽

Sensitivity Specificity

Abstract Background Non-invasive prenatal screening (NIPS) is widely used as the alternative choice for pregnant women at high-risk of fetal aneuploidy. However, whether NIPS has a good detective efficiency for pregnant women at advanced maternal age (AMA) has not been fully studied especially in Chinese women. Methods Twenty-nine thousand three hundred forty-three pregnant women at AMA with singleton pregnancy who received NIPS and followed-up were recruited. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), receiver operating characteristic (ROC) curves and the Youden Index for detecting fetal chromosomal aneuploidies were analyzed. The relationship between maternal age and common fetal chromosomal aneuploidy was observed. Results The sensitivity, specificity, PPV, NPV of NIPS for detecting fetal trisomy 21 were 99.11, 99.96, 90.98, and 100%, respectively. These same parameters for detecting fetal trisomy 18 were 100, 99.94, 67.92, and 100%, respectively. Finally, these parameters for detecting trisomy 13 were 100, 99.96, 27.78, and 100%, respectively. The prevalence of fetal trisomy 21 increased exponentially with maternal age. The high-risk percentage incidence rate of fetal trisomy 21 was significantly higher in the pregnant women at 37 years old or above than that in pregnant women at 35 to 37 years old. (Youden index = 37). Conclusion It is indicated that NIPS is an effective prenatal screening method for pregnant women at AMA.

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The underestimated issue of non-reproducible cardiac troponin I and T results: case series and systematic review of the literature

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-1564 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Julien Favresse ◽

Jean-Louis Bayart ◽

Damien Gruson ◽

Sergio Bernardini ◽

Aldo Clerico ◽

...

Keyword(s):

Systematic Review ◽

Clinical Judgment ◽

Troponin I ◽

Troponin T ◽

Case Reports ◽

False Negative ◽

Case Series ◽

Elevated Alkaline Phosphatase ◽

Negative Results ◽

Significant Difference

Abstract Cardiac troponins (cTn) are the preferred biomarkers for the evaluation of myocardial injury and play a key role in the diagnosis of acute myocardial infarction (MI). Pre-analytical or analytical issues and interferences affecting troponin T and I assays are therefore of major concern given the risk of misdiagnosis. False positive troponin results have been related to various interferences including anti-troponin antibodies, heterophilic antibodies, or elevated alkaline phosphatase level. On the other hand, false negative results have been reported in the case of a large biotin intake. These interferences are characterized with erroneous but reproducible troponin results. Of interest, non-reproducible results have also been reported in the literature. In other words, if the sample is reanalyzed a second time, a significant difference in troponin results will be observed. These interferences have been named “fliers” or “outliers”. Compared to the biotin interference that received major attention in the literature, troponin outliers are also able to induce harmful clinical consequences for the patient. Moreover, the prevalence of outliers in recent studies was found to be higher (0.28–0.57%) compared to the biotin interference. The aim of this systematic review is to warn clinicians about these non-reproducible results that may alter their clinical judgment. Four case reports that occurred in the Clinique of Saint-Luc Bouge are presented to attest this point. Moreover, we aimed at identifying the nature of these non-reproducible troponin results, determining their occurrence, and describing the best way for their identification.

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Routinization of prenatal screening with the non-invasive prenatal test: pregnant women’s perspectives

European Journal of Human Genetics ◽

10.1038/s41431-021-00940-8 ◽

2021 ◽

Author(s):

Karuna R. M. van der Meij ◽

Annabel Njio ◽

Linda Martin ◽

Janneke T. Gitsels-van der Wal ◽

Mireille N. Bekker ◽

...

Keyword(s):

Down Syndrome ◽

Pregnant Women ◽

Prenatal Screening ◽

Screening Program ◽

Informed Choice ◽

Aneuploidy Screening ◽

Non Invasive ◽

Fetal Aneuploidy ◽

Societal Pressure ◽

Prenatal Test

AbstractDue to the favorable test characteristics of the non-invasive prenatal test (NIPT) in the screening of fetal aneuploidy, there has been a strong and growing demand for implementation. In the Netherlands, NIPT is offered within a governmentally supported screening program as a first-tier screening test for all pregnant women (TRIDENT-2 study). However, concerns have been raised that the test’s favorable characteristics might lead to uncritical use, also referred to as routinization. This study addresses women’s perspectives on prenatal screening with NIPT by evaluating three aspects related to routinization: informed choice, freedom to choose and (personal and societal) perspectives on Down syndrome. Nationwide, a questionnaire was completed by 751 pregnant women after receiving counseling for prenatal screening. Of the respondents, the majority (75.5%) made an informed choice for prenatal screening as measured by the multidimensional measure of informed choice (MMIC). Education level and religious affiliation were significant predictors of informed choice. The main reason to accept screening was “seeking reassurance” (25.5%), and the main reason to decline was “every child is welcome” (30.6%). The majority of respondents (87.7%) did not perceive societal pressure to test. Differences between test-acceptors and test-decliners in personal and societal perspectives on Down syndrome were found. Our study revealed high rates of informed decision-making and perceived freedom to choose regarding fetal aneuploidy screening, suggesting that there is little reason for concern about routinization of NIPT based on the perspectives of Dutch pregnant women. Our findings highlight the importance of responsible implementation of NIPT within a national screening program.

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Follow-up in Patients With Non-invasive Prenatal Screening Failures: A Reflection on the Choice of Further Prenatal Diagnosis

Frontiers in Genetics ◽

10.3389/fgene.2021.666648 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sha Liu ◽

Hongqian Liu ◽

Jianlong Liu ◽

Ting Bai ◽

Xiaosha Jing ◽

...

Keyword(s):

Genetic Counseling ◽

Prenatal Diagnosis ◽

Pregnant Women ◽

Prenatal Screening ◽

Chromosomal Abnormalities ◽

Detection Methods ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Non Invasive

BackgroundOur aim was to provide a theoretical basis for clinicians to conduct genetic counseling and choose further prenatal diagnosis methods for pregnant women who failed non-invasive prenatal screening (NIPS).MethodsA retrospective analysis was performed on pregnant women who had failed NIPS tests.ResultsAmong the 123,291 samples, 394 pregnant women did not obtain valid results due to test failures. A total of 378 pregnant women were available for follow-up, while 16 patients were lost to follow-up. Of these 378, 135 pregnant women chose further prenatal diagnosis through amniocentesis, and one case of dysplasia was recalled for postpartum chromosome testing. The incidence rate of congenital chromosomal abnormalities in those who failed the NIPS was 3.97% (15/378), which was higher than that of the chromosomal abnormalities in the common population (1.8%). Among the pregnant women who received prenatal diagnosis, the positive rates of chromosomal abnormalities in the chromosomal microarray analysis/copy number variation sequencing (CMA/CNV-seq) group and in the karyotyping group were 15.28 and 4.76%, respectively.ConclusionPrenatal diagnosis should be strongly recommended in posttest genetic counseling for pregnant women with NIPS failures. Further, high-resolution detection methods should be recommended for additional prenatal diagnoses.

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