scholarly journals Comprehensive non-invasive prenatal screening for pregnancies with elevated risks of genetic disorders: protocol for a prospective, multicentre study

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e053617
Author(s):  
Chenming Xu ◽  
Xiaoqiang Cai ◽  
Songchang Chen ◽  
Qiong Luo ◽  
Hui Xi ◽  
...  
Keyword(s):  
Prenatal Screening ◽  
Chromosomal Abnormalities ◽  
Genetic Disorders ◽  
Treatment Options ◽  
Copy Number Variations ◽  
Outcome Data ◽  
Predictive Values ◽  
Clinical Sensitivity ◽  
Monogenic Disorders ◽  
Non Invasive

IntroductionChromosomal abnormalities and monogenic disorders account for ~15%–25% of recognisable birth defects. With limited treatment options, preconception and prenatal screening were developed to reduce the incidence of such disorders. Currently, non-invasive prenatal screening (NIPS) for common aneuploidies is implemented worldwide with superiority over conventional serum or sonographic screening approaches. However, the clinical validity for the screening of frequent chromosome segmental copy number variations and monogenic disorders still awaits to be proved.Methods and analysisThis study is a multicentre, prospective study. The participants were recruited from three tertiary hospitals in China starting from 10 April 2021. The study is expected to conclude before 10 October 2022. Pregnant women with abnormal prenatal screening results indicated for invasive prenatal diagnosis or those who decide to terminate their pregnancies due to abnormal ultrasound findings will be evaluated for enrolment. Cell-free DNA extracted from the maternal plasma will be used for an analytically validated comprehensive NIPS test developed by Beijing BioBiggen Technology Co. (Beijing, China). The diagnostic results from prenatal or postnatal specimens as well as the pregnancy outcome data will be collected to examine the clinical sensitivity, specificity, positive and negative predictive values of the test.Ethics and disseminationThis study was approved by the Obstetrics and Gynecology Hospital of Fudan University (2020-178). Results of this study will be disseminated to public through scientific conferences and a peer-reviewed journal. Written informed consents will be obtained from participants.Trial registration numberChiCTR2100045739.

scholarly journals Assessment of a change of protocol of prenatal screening by inclusion of non-invasive prenatal diagnosis

2020 ◽  
Vol 1 (2) ◽  
Author(s):  
Rocío Cabra-Rodríguez ◽  
Guadalupe Bueno Rodríguez ◽  
Cristina Santos Rosa ◽  
Miguel Ángel Castaño López ◽  
Sonia Delgado Muñoz ◽  
...  
Keyword(s):  
Prenatal Screening ◽  
Chromosomal Abnormalities ◽  
Screening Program ◽  
High Sensitivity ◽  
Maternal Blood ◽  
Screening Tests ◽  
Loss To Follow Up ◽  
Non Invasive ◽  
Second Trimester Screening ◽  
Trimester Screening

AbstractObjectivesNon-invasive prenatal screening (NIPS) is a test for the detection of major fetal chromosomal abnormalities in maternal blood during pregnancy. The purpose of this study was to assess the performance of NIPS implemented within the framework of the Screening Program for Congenital Abnormalities of the Andalusian Health System.MethodsA retrospective observational study was undertaken to determine the number of NIPS tests performed since its introduction. The number of invasive diagnostic tests done after the implementation of NIPS in the patients included in the program between March 2016 and August 2017 was also quantified.ResultsA total of 6,258 combined first- and second trimester screening tests were performed, covering 95% of the population. In total, 250 subjects were identified as high risk, of whom 200 underwent NIPS after loss to follow-up. NIPS showed a sensitivity of 100% (95% CI: 76.84–100%) and a specificity of 99.46% (95% CI: 97.04–99.99%).ConclusionsThis test has proven to have a very high sensitivity and specificity. The results obtained demonstrate that the incorporation of NIPS in clinical practice minimizes the rate of miscarriages and reduces the frequency of invasive procedures by 70%.

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

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.

scholarly journals The Value of Non-Invasive Prenatal Testing in the Diagnosis of Birth Defects: Insights from a Large Multicentre Study in Southern China

2021 ◽  
Author(s):  
Meiying Cai ◽  
Na Lin ◽  
Xuemei Chen ◽  
Ying Li ◽  
Min Lin ◽  
...  
Keyword(s):  
Multicentre Study ◽  
Pregnant Women ◽  
Chromosomal Abnormalities ◽  
Southern China ◽  
Prenatal Testing ◽  
Copy Number Variations ◽  
Trisomy 13 ◽  
Detection Rates ◽  
Non Invasive ◽  
Large Multicentre Study

Abstract Non-invasive prenatal testing (NIPT) is a fast, safe, and non-disruptive diagnostic method. At present, few studies have evaluated the screening efficiency of NIPT positive predictive value (PPV) in study subjects. Here, the results of NIPT in pregnant women were retrospectively analysed, and the detection rate, PPV and follow-up data were evaluated to determine its clinical value. A large multicentre study was conducted involving 52,855 pregnant women who received NIPT. Based on gestational age, amniotic fluid or umbilical cord blood were extracted for simultaneous karyotype and chromosome microarray analysis (CMA) in NIPT-positive patients. Among the 52,855 cases, 754 were NIPT-positive, with a positivity rate of 1.4%. Karyotype analysis and/or CMA confirmed 323 cases of chromosomal abnormalities, with a PPV of 45.1%. PPV of Trisomy 21 (T21), Trisomy 18 (T18), Trisomy 13 (T13), sex chromosomal aneuploidies (SCA) and copy number variations (CNV) were 78.9%, 35.3%, 22.2%, 36.9% and 32.9%, respectively. The PPV of T21, T18, and T13 increased with age whereas, the PPV of SCA and CNVs had little correlation with age. The PPV was significantly high in patients with advanced age along with an abnormal ultrasound.NIPT had a high PPV for T21, and a low PPV for T13 and T18, while screening for SCA and CNVs showed clinical significance. However, in case of NIPT screening for SCA and CNVs, simultaneous karyotype and CMA should be performed to increase the detection rates. Interventional prenatal diagnosis is still required in NIPT-positive cases to avoid false positives or unnecessary termination of pregnancy.

scholarly journals Comprehensive Evaluation of Non-invasive Prenatal Screening to Detect Fetal Copy Number Variations

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Wang ◽  
Bin Zhang ◽  
Lingna Zhou ◽  
Qin Zhou ◽  
Yingping Chen ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Pregnant Women ◽  
Copy Number ◽  
Prenatal Screening ◽  
Comprehensive Evaluation ◽  
Copy Number Variations ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Non Invasive ◽  
Pathogenic Cnvs

ObjectiveTo evaluate the effectiveness of non-invasive prenatal screening (NIPS) in prenatal screening of fetal pathogenic copy number variants (CNVs).Materials and MethodsWe evaluated the prenatal screening capacity using traditional and retrospective approaches. For the traditional method, we evaluated 24,613 pregnant women who underwent NIPS; cases which fetal CNVs were suggested underwent prenatal diagnosis with chromosomal microarray analysis (CMA). For the retrospective method, we retrospectively evaluated 47 cases with fetal pathogenic CNVs by NIPS. A systematic literature search was performed to compare the evaluation efficiency.ResultsAmong the 24,613 pregnant women who received NIPS, 124 (0.50%) were suspected to have fetal CNVs. Of these, 66 women underwent prenatal diagnosis with CMA and 13 had true-positive results. The positive predictive value (PPV) of NIPS for fetal CNVs was 19.7%. Among 1,161 women who did not receive NIPS and underwent prenatal diagnosis by CMA, 47 were confirmed to have fetal pathogenic CNVs. Retesting with NIPS indicated that 24 of these 47 cases could also be detected by NIPS, representing a detection rate (DR) of 51.1%. In total, 10 publications, namely, six retrospective studies and four prospective studies, met our criteria and were selected for a detailed full-text review. The reported DRs were 61.10–97.70% and the PPVs were 36.11–80.56%. The sizes of CNVs were closely related to the accuracy of NIPS detection. The DR was 41.9% (13/31) in fetuses with CNVs ≤ 3 Mb, but was 55.0% (11/20) in fetuses with CNVs > 3 Mb. Finally, to intuitively show the CNVs accurately detected by NIPS, we mapped all CNVs to chromosomes according to their location, size, and characteristics. NIPS detected fetal CNVs in 2q13 and 4q35.ConclusionThe DR and PPV of NIPS for fetal CNVs were approximately 51.1% and 19.7%, respectively. Follow-up molecular prenatal diagnosis is recommended in cases where NIPS suggests fetal CNVs.

scholarly journals 930: Clinical utility of non-invasive prenatal screening for common dominant monogenic disorders

2019 ◽  
Vol 220 (1) ◽  
pp. S599
Author(s):  
YE CAO ◽  
Yanjun Jiang ◽  
Anne Clinger ◽  
Sandra Peacock ◽  
Eric Schmitt ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Prenatal Screening ◽  
Monogenic Disorders ◽  
Non Invasive

Non-invasive prenatal screening of fetal sex chromosomal abnormalities: perspective of pregnant women

2012 ◽  
Vol 25 (12) ◽  
pp. 2616-2619 ◽  
Author(s):  
Tze Kin Lau ◽  
Mei Ki Chan ◽  
Pui Shan Salome Lo ◽  
Hon Yee Connie Chan ◽  
WaiSze Kim Chan ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Prenatal Screening ◽  
Chromosomal Abnormalities ◽  
Fetal Sex ◽  
Non Invasive

Challenges in non-invasive prenatal screening for sub-chromosomal copy number variations using cell-free DNA

2017 ◽  
Vol 37 (11) ◽  
pp. 1067-1075 ◽  
Author(s):  
Henna V. Advani ◽  
Angela N. Barrett ◽  
Mark I. Evans ◽  
Mahesh Choolani
Keyword(s):  
Copy Number ◽  
Prenatal Screening ◽  
Copy Number Variations ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Chromosomal Copy Number ◽  
Chromosomal Copy

scholarly journals Relevance of Invasive Testing in Era of Non-Invasive Testing for Prenatal Chromosomal Abnormalities

2020 ◽  
pp. 1
Author(s):  
Abhijeet Kumar ◽  
Madhusudan Dey ◽  
Devendra Arora
Keyword(s):  
Diagnostic Tests ◽  
Prenatal Screening ◽  
Chromosomal Abnormalities ◽  
Chorionic Villus ◽  
Prenatal Testing ◽  
Maternal Serum ◽  
Chorionic Villus Sampling ◽  
Non Invasive ◽  
Fetal Dna ◽  
Cell Free Fetal Dna

<p>Prenatal screening for chromosomal abnormalities has two components i.e. prenatal screening (maternal serum screening and cell-free fetal DNA screening) and prenatal diagnosis (chorionic villus sampling, amniocentesis, and cordocentesis). Prenatal testing in the past decade is evolving towards non-invasive methods to determine the chromosome abnormality disorders in the fetus without incurring the risk of miscarriage. Conventional tools for prenatal screening included maternal age, maternal serum markers, ultrasound marker (nuchal thickness), and their combinations. With the increased risk of screening test patients were offered diagnostic tests (chorionic villus sampling, amniocentesis, and cordocentesis). After the availability of noninvasive prenatal tests for commercial use in 2011, a great marketing drive is there to establish it as a master tool for prenatal testing. However various society guidelines i.e. ACOG, RCOG, and ISUOG have clearly stated that cell-free fetal DNA based noninvasive prenatal tests is a screening test, not a diagnostic test. In the succeeding paragraph, we will review current trends in the field of cell-free fetal DNA noninvasive prenatal tests and the relevance of invasive testing in the context of noninvasive prenatal tests. Noninvasive prenatal tests does not entirely replace invasive prenatal testing procedures. Positive noninvasive prenatal tests findings must be confirmed by diagnostic tests based on an invasive sample source, mainly chorionic villus sampling or amniocentesis due to false positive and false negative reports of cell-free fetal DNA based tests. Continuing research and development efforts are focused on overriding noninvasive prenatal tests limitations. Recent studies show that procedure-associated risks in the case of prenatal invasive testing are very low as compared to previous studies. Prenatal invasive testing will remain as the backbone of prenatal diagnostic testing until the limitation of noninvasive prenatal tests is overcome.</p>

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