{"id":85790,"date":"2020-07-01T09:19:11","date_gmt":"2020-07-01T00:19:11","guid":{"rendered":"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/"},"modified":"2025-08-11T10:38:34","modified_gmt":"2025-08-11T01:38:34","slug":"nipt-cohort-study","status":"publish","type":"post","link":"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en","title":{"rendered":"A cohort study to detect aneuploidies and autosomal partial deletions and duplications using NIPT in 42,910 pregnant women (singleton) with different clinical features"},"content":{"rendered":"\n<div class=\"wp-block-group nipu-report\"><div class=\"wp-block-group__inner-container is-layout-flow wp-block-group-is-layout-flow\">\n<h2 class=\"wp-block-heading hidden-heading\"><\/h2>\n\n\n\n<p>Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions\/ microduplications in a cohort of 42,910 single pregnancies with different clinical features<\/p>\n<\/div><\/div>\n\n\n\n<div class=\"wp-block-group author\"><div class=\"wp-block-group__inner-container is-layout-flow wp-block-group-is-layout-flow\">\n<p>Yibo Chen<sup>1<\/sup>, Qi Yu<sup>1<\/sup>, Xiongying Mao<sup>1<\/sup>, Wei Lei<sup>2<\/sup>, Miaonan He<sup>3<\/sup> and Wenbo Lu<sup>1*<\/sup><\/p>\n\n\n\n<p><sup>1<\/sup>Ningbo Women and Children Hospital, No.339, Liuting Street, Haishu District Ningbo, Ningbo 315010, China<\/p>\n<\/div><\/div>\n\n\n\n<section class=\"note_table table_0\">\n<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_83 counter-hierarchy ez-toc-counter ez-toc-grey ez-toc-container-direction\">\n<div class=\"ez-toc-title-container\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">\u76ee\u6b21<\/p>\n<span class=\"ez-toc-title-toggle\"><a href=\"#\" class=\"ez-toc-pull-right ez-toc-btn ez-toc-btn-xs ez-toc-btn-default ez-toc-toggle\" aria-label=\"Toggle Table of Content\"><span class=\"ez-toc-js-icon-con\"><span class=\"\"><span class=\"eztoc-hide\" style=\"display:none;\">Toggle<\/span><span class=\"ez-toc-icon-toggle-span\"><svg style=\"fill: #999;color:#999\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" class=\"list-377408\" width=\"20px\" height=\"20px\" viewBox=\"0 0 24 24\" fill=\"none\"><path d=\"M6 6H4v2h2V6zm14 0H8v2h12V6zM4 11h2v2H4v-2zm16 0H8v2h12v-2zM4 16h2v2H4v-2zm16 0H8v2h12v-2z\" fill=\"currentColor\"><\/path><\/svg><svg style=\"fill: #999;color:#999\" class=\"arrow-unsorted-368013\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"10px\" height=\"10px\" viewBox=\"0 0 24 24\" version=\"1.2\" baseProfile=\"tiny\"><path d=\"M18.2 9.3l-6.2-6.3-6.2 6.3c-.2.2-.3.4-.3.7s.1.5.3.7c.2.2.4.3.7.3h11c.3 0 .5-.1.7-.3.2-.2.3-.5.3-.7s-.1-.5-.3-.7zM5.8 14.7l6.2 6.3 6.2-6.3c.2-.2.3-.5.3-.7s-.1-.5-.3-.7c-.2-.2-.4-.3-.7-.3h-11c-.3 0-.5.1-.7.3-.2.2-.3.5-.3.7s.1.5.3.7z\"\/><\/svg><\/span><\/span><\/span><\/a><\/span><\/div>\n<nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#When_examining_42910_singleton_pregnant_women\" >When examining 42,910 singleton pregnant women<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Summary\" >#Summary<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Consideration_of_the_above_paper\" >Consideration of the above paper<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-4\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Introduction\" >Introduction<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-5\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Results\" >Results<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-6\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Patient_background\" >Patient background<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-7\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Prenatal_test_results_for_all_pregnancies\" >Prenatal test results for all pregnancies<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-8\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#NIPT_results_for_T21_T18_T13_and_SCA\" >NIPT results for T21, T18, T13, and SCA<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-9\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Table_1_Clinical_characteristics_of_pregnant_women_undergoing_NIPT\" >Table 1 Clinical characteristics of pregnant women undergoing NIPT<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-10\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#NIPT_results_for_CNV_and_other_chromosomal_aneuploidies\" >NIPT results for CNV and other chromosomal aneuploidies<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-11\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Table_2_Performance_of_non-invasive_prenatal_testing_NIPT_chromosome_aneuploidy\" >Table 2 Performance of non-invasive prenatal testing (NIPT) chromosome aneuploidy<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-12\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Inspection\" >Inspection<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-13\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Table_3_Size_and_number_of_CNVs_and_other_chromosomal_aneuploidies_on_each_chromosome\" >Table 3 Size and number of CNVs and other chromosomal aneuploidies on each chromosome<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-14\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Table_4_PPV_according_to_CNV_size\" >Table 4 PPV according to CNV size<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-15\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Table_5_Different_PPV_depending_on_pregnancy_characteristics\" >Table 5 Different PPV depending on pregnancy characteristics<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-16\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Conclusion\" >Conclusion<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-17\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Materials_and_methods\" >Materials and methods<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-18\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Serological_screening_and_ultrasound_examination\" >Serological screening and ultrasound examination<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-19\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Allocation_decision\" >Allocation decision<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-20\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Karyotype_analysis_and_amniocentesis\" >Karyotype analysis and amniocentesis<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-21\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Follow-up_of_negative_cases\" >Follow-up of negative cases<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-22\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Statistical_analysis\" >Statistical analysis<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-23\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Abbreviation\" >Abbreviation<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-24\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Thank_you\" >Thank you<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-25\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Author_contributions\" >Author contributions<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-26\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Fund_transfer\" >Fund transfer<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-27\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Availability_of_data_and_materials\" >Availability of data and materials<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-28\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Ethical_acknowledgment_and_consent_to_participate\" >Ethical acknowledgment and consent to participate<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-29\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Consent_to_publication\" >Consent to publication<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-30\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Contrary_interests\" >Contrary interests<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-31\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Author_details\" >Author details<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-32\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#References\" >References<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-33\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\/#Publishers_Note\" >Publisher&#8217;s Note<\/a><\/li><\/ul><\/li><\/ul><\/nav><\/div>\n<h3><span class=\"ez-toc-section\" id=\"When_examining_42910_singleton_pregnant_women\"><\/span>When examining 42,910 singleton pregnant women<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<table>\n<thead>\n<tr>\n<th><\/th>\n<th>21<\/th>\n<th>18<\/th>\n<th>13<\/th>\n<th>Sex chromosomes<\/th>\n<th>Whole chromosome<\/th>\n<th>Deletion\/duplication<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<th data-total=\"535\">Number of positives<\/th>\n<td data-count=\"155\">155<\/td>\n<td data-count=\"44\">44<\/td>\n<td data-count=\"33\">33<\/td>\n<td data-count=\"147\">147<\/td>\n<td data-count=\"47\">47<\/td>\n<td data-count=\"109\">109<\/td>\n<\/tr>\n<tr>\n<th>Positive cut<\/th>\n<td>28.97%<\/td>\n<td>8.22%<\/td>\n<td>6.17%<\/td>\n<td>27.48%<\/td>\n<td>8.79%<\/td>\n<td>20.37%<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/section>\n\n\n<section>\n<h2><span class=\"ez-toc-section\" id=\"Summary\"><\/span>#Summary<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p><strong>Background:<\/strong> Since the discovery of cell-free DNA (cfDNA) in maternal plasma, it has opened a new approach for non-invasive prenatal testing. With the progress of whole genome sequencing, <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> has discovered partial deletion\/duplication diseases of all autosomal regions. This study reviewed the effectiveness of <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> as a screening test for aneuploidy and CNV (copy number variation) in 42,910 single pregnancies. <\/p>\n<p><strong>Methods:<\/strong> A total of 42,910 single pregnancies with different clinical characteristics were recruited. Cell-free fetal DNA was directly sequenced. Chromosomal aneuploidy and all autosomal partial deletion\/duplication diseases were analyzed. <\/p>\n<p><strong>Results:<\/strong> A total of 534 pregnancies (1.24%) had abnormal results detected by <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a>, and 403 pregnancies had undergone prenatal diagnosis. The positive predictive value (PPV) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidy (SCA), and other chromosome aneuploidies were 79.23% and 54.84%, respectively. They were 13.79%, 33.04% and 9.38%. The PPV of CNV was 28.99%. The PPV for CNV\u22665 Mb was 20.83%, 5-10 Mb 50.00%, &gt;10 Mb 27.27%. The PPV of <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> also differs depending on pregnancy characteristics. <\/p>\n<p><strong>Conclusion:<\/strong> Our data are potentially important in demonstrating the utility of <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> profiling not only for common whole-chromosome aneuploidies but also for CNVs. However, this modern method is still in its infancy for CNV. Clinical validation studies with accurate detection rates and false-positive rates in clinical practice are still needed. <\/p>\n<p><strong>Keywords:<\/strong>Non-invasive prenatal testing (<a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a>), chromosomal aneuploidy, whole autosomal partial deletion\/duplication disease (MMS), clinical features, positive predictive value (PPV)<\/p>\n<\/section>\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Consideration_of_the_above_paper\"><\/span>Consideration of the above paper<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>According to a paper by Chen et al. published in 2019, trisomy 21 is 155\/42910=1\/276, trisomy 18 is 44\/42910=1\/975, and trisomy 13 is 33\/42910=1\/1300. It is occurring in proportion. This corresponds to the inspection items that we usually call the O set. In addition, the test content is the same as that carried out by the <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> consortium in Japan. On the other hand, the frequency of occurrence of sex chromosomes is 147\/42910=1\/291, which is the second highest frequency after chromosome 21. This is what would be detected in the O+ set or A set in our inspection. Because developmental delays such as decreased intelligence are rare, they are not tested, but they are relatively common. In addition, all chromosomes included in the D+ set that we are conducting, all autosomal whole region partial deletion\/duplication diseases have an incidence rate of (47+109)\/42910=1\/275, which is about the same as trisomy 21. . Until now, the D set, which detects partial deletion diseases of all autosomal regions only in specific regions 1.4, 5, 15, and 22, has not occurred very often, but It is reported that this happens frequently. However, for cases of aneuploidy of all chromosomes or chromosome 13, which occur less frequently, the positive predictive value is relatively low. If <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> is positioned as a screening test, there may be some things that can&#8217;t be helped. Also, I have the impression that overall the number of positive cases is lower than at our facility. This is thought to be because in the population sampled in this paper, the proportion of pregnant women aged 35 years or older was 25.03%, which is lower than that at Hiro Clinic. At Hiro Clinic <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a>, the number seems to be even higher, but the above percentage of positive frequency is similar to what we feel. <\/p>\n<\/section>\n\n\n<p><\/p>\n<hr>\n<p><\/p>\n\n<div class=\"author\">Yibo Chen1, Qi Yu1, Xiongying Mao1, Wei Lei2, Miaonan He3 and Wenbo Lu1*<\/div>\n\n\n\n<div class=\"lead\">\n<p>Author 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:\/\/creativecommons.org\/licenses\/by\/4.0\/). This license permits unrestricted use, distribution, and reproduction in any medium. provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Disclaimer (http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/) applies to the data available in this section, unless otherwise noted. <\/p><\/div>\n\n\n\n<section>\n<h2><span class=\"ez-toc-section\" id=\"Introduction\"><\/span>Introduction<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p>Since the discovery of cell-free fetal DNA (cffDNA) in triterminal plasma in 1997 [1], it has opened a new approach for non-invasive prenatal testing (<a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a>). Since 2011, massively parallel sequencing (MPS) for embryonic polyploids has been available in more than 60 countries. <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a>, which uses cfDNA circulating in maternal blood, opens the door to early, accurate, and safe prenatal testing and has been used clinically for more than eight years [2]. 21, 18, 13 The weighted pooled detection and false positive rates of screening for monosomy reported as 90.3% (0.23%) and 93% (0.14%) [3]. <br>\nA growing number of studies indicate that <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> may reduce the incidence of unnecessary invasive procedures and iatrogenic fetal loss [4]. <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> had many additional advantages over traditional biochemical and ultrasound screening, such as higher sensitivity and specificity and the ability to perform <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> at earlier gestational ages. In China, <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> is restarted for trisomy 21 (T21), T18, and T13 screening for patients at high risk for late pregnancy serological screening results [5]. Currently, an increasing number of pregnant women are choosing <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> [6, 7]. <br>\nThis advanced prenatal screening method has other applications, including screening for all autosomal deletion\/duplication diseases (MMS) caused by copy number variants (CNVs) smaller than 10 Mb. Although individually rare, MMS accounts for 1-2% of genital abnormalities in newborns and often imposes a heavy burden on families and society. Recently, further development and expansion of <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> has focused on MMS such as Hu et al. [8] and Liang et al. [9] demon-strated <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> showed good results in some MMS. <br>\nHowever, there are many problems and challenges in clinical practice, and extensive verification is required to make a decision. <br>\nAccurate Detection Rate and False-Positive Rate The purpose of this study was to review the effectiveness of <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> as a screening test for aneuploidy and CNV in 42,910 single pregnancies. <\/p>\n<\/section>\n\n<section>\n<h2><span class=\"ez-toc-section\" id=\"Results\"><\/span>Results<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<h3><span class=\"ez-toc-section\" id=\"Patient_background\"><\/span>Patient background<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>From April 2015 to December 2018, a total of 42,931 maternal blood samples were collected from Ningbo Women&#8217;s and Children&#8217;s Hospital, China. Twenty-one cases failed, resulting in a failure rate of 0.05%. Therefore, the total sample included in this study was 42,910. The gestational age ranged from 12+0 to 26+6, the age ranged from 18 to 49 years, and there were 10,742 women with older maternal age (35 years or older). The clinical characteristics of the 42,910 cases are shown in Table 1. Of these 42,910 specimens, 348 pregnant women required resampling due to low fetal DNA concentration in plasma, and the resampling rate was 0.81% (348\/42910), and all resamplings resulted in <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> results. obtained (Table 1). <\/p>\n\n<h3><span class=\"ez-toc-section\" id=\"Prenatal_test_results_for_all_pregnancies\"><\/span>Prenatal test results for all pregnancies<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>Before <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a>, pregnant women undergo traditional tube screening tests including fetal ultrasound (including color ultrasound and 3-dimensional color ultrasound) and maternal serum biomarkers. Ultrasonography showed that 202 (0.47%) fetuses were structurally abnormal and there were 5749 (13.4%) fetuses with increased NT (NT \u2265 3 mm). Measurement of maternal serum biomarkers suggested 2318 (5.4%) high-risk pregnancies, 15,863 (36.97%) critical-risk pregnancies, and no clinical indication in 8024 (18.70%) pregnancies. (Table 1). <\/p>\n\n<h3><span class=\"ez-toc-section\" id=\"NIPT_results_for_T21_T18_T13_and_SCA\"><\/span>NIPT results for T21, T18, T13, and SCA<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>The flowchart is shown in Figure 1. A total of 42,931 specimens were recruited and 42,910 <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> results were obtained. <\/p>\n<\/section>\n\n<section class=\"note_table table_1\">\n<h3><span class=\"ez-toc-section\" id=\"Table_1_Clinical_characteristics_of_pregnant_women_undergoing_NIPT\"><\/span>Table 1 Clinical characteristics of pregnant women undergoing NIPT<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<table>\n<thead>\n<tr>\n<th>Gestational age at <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> (weeks)<\/th>\n<th>Number\/N = 42910<\/th>\n<th>Ratio (%)<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<td>12~15+6<\/td>\n<td>5535<\/td>\n<td>12.90<\/td>\n<\/tr>\n<tr>\n<td>16~19+6<\/td>\n<td>24759<\/td>\n<td>57.70<\/td>\n<\/tr>\n<tr>\n<td>20~23+6<\/td>\n<td>10513<\/td>\n<td>24.50<\/td>\n<\/tr>\n<tr>\n<td>24~26+6<\/td>\n<td>2103<\/td>\n<td>4.90<\/td>\n<\/tr>\n<\/tbody>\n<thead>\n<tr><th>Clinical characteristics<\/th>\n<th>No.<\/th>\n<th>Ratio (%)<\/th>\n<\/tr><\/thead>\n<tbody>\n<tr>\n<td>B-Structural abnormalities of the fetus determined by ultrasound examination<\/td>\n<td>202<\/td>\n<td>0.47<\/td>\n<\/tr>\n<tr>\n<td>NT increase<\/td>\n<td>5749<\/td>\n<td>13.4<\/td>\n<\/tr>\n<tr>\n<td>Other a<\/td>\n<td>12<\/td>\n<td>0.03<\/td>\n<\/tr>\n<tr>\n<td>High risk of serological screening<\/td>\n<td>2318<\/td>\n<td>5.40<\/td>\n<\/tr>\n<tr>\n<td>Significant risks of serological screening<\/td>\n<td>15863<\/td>\n<td>36.97<\/td>\n<\/tr>\n<tr>\n<td>Mother&#8217;s age is older (\u226735 years)<\/td>\n<td>10742<\/td>\n<td>25.03<\/td>\n<\/tr>\n<tr>\n<td>No clinical indication<\/td>\n<td>8024<\/td>\n<td>18.70<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p class=\"table_comment\">Patients with contraindications for interventional surgery: reoperation infection, placenta previa, placental hemorrhage, poor pregnancy history<\/p>\n<\/section>\n\n<section>\n<p>Abnormal results in 534 cases (1.24%). Of these 534 cases, 155 of trisomy 21 (T21), 44 of T18, 33 of T13, 147 of sex chromosome aberrations (SCA), and other chromosomal aneuploidies (T21, T18, T13, sex chromosome (excluding aneuploidies) and 109 of CNVs. <br>\nKaryotypes were obtained to verify the abnormal results of <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> prediction. The total abnormal results for T21, T18, T13, and SCA were 379. Of these 379 cases, 302 underwent prenatal diagnostic testing, resulting in 161 true positives (103 for T21, 17 for T18, 4 for T13, and 37 for SCA) and 141 false positives (FP ) was confirmed. Additionally, the positive predictive value (PPV) of each test was evaluated. For trisomy 21, the PPV was 79.23%, for trisomy 18 54.84%, for trisomy 13 13.79%, and for SCA 33.04% (Table 2 and Figure 1). <\/p>\n\n<h3><span class=\"ez-toc-section\" id=\"NIPT_results_for_CNV_and_other_chromosomal_aneuploidies\"><\/span>NIPT results for CNV and other chromosomal aneuploidies<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>In addition, since this technology is genome-wide sequencing, we analyzed CNVs and other chromo-some aneuploidies. The total cases of CNV abnormalities are as follows. <br>\nOf the 109 cases, 20 were true positives, 49 were false positives, and 50 were unconfirmed. The number and size of CNVs on each chromosome were evaluated. CNVs were classified into three groups according to length: CNV\u2266Mb, CNV within 5-10 Mb, and CNV >10 Mb. PPV of each group was also evaluated. The total PPV of CNV was 28.99%. The PPV for CNVs below 5 Mb is 20.83%, 50.00% for CNVs between 5 and 10 Mb, and 27.27% for CNVs above 10 Mb. The total number of cases of other chromosomal aneuploidies was 46, including 3 true positives, 29 false positives, and 14 unconfirmed cases. The PPV of other chromosomal aneuploidies was 9.38%. Among other chromosomal aneuploidies, Chr7 aneuploidy is the largest group. Although all Chr7 aneuploidies predicted by <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> are trisomy 7, all confirmed patients (total number of 9) were confirmed to be false positives (Tables 3 and 4). <\/p>\n\n<p>Differences in PPV depending on pregnancy characteristics Table 5 shows differences in PPV of <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> depending on pregnancy characteristics. The total PPV of T21 is 79.23%, and the PPV of T21 fetuses in women with older maternal age is 89.29%, and in high-risk groups of serological screening, as follows<\/p>\n<\/section>\n\n\n<section class=\"note_table table_2\">\n<h3><span class=\"ez-toc-section\" id=\"Table_2_Performance_of_non-invasive_prenatal_testing_NIPT_chromosome_aneuploidy\"><\/span>Table 2 Performance of non-invasive prenatal testing (NIPT) chromosome aneuploidy<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<table>\n<tbody><tr><th><a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a><\/th><th>Positive<\/th><th>True Positive<\/th><th>False Positive<\/th><th>PPV<\/th><\/ tr>\n<tr><th>T21<\/th><td class=\"tr21\">155<\/td><td class=\"tr21\">103<\/td><td class=\"tr21\">27<\/td><td class=\"tr21\">79.23%<\/td><\/tr>\n<tr><th>T18<\/th><td class=\"tr18\">44<\/td><td class=\"tr18\">17<\/td><td class=\"tr18\">14<\/td><td class=\"tr18\">54.84%<\/td><\/tr>\n<tr><th>T13<\/th><td class=\"tr13\">33<\/td><td class=\"tr13\">4<\/td><td class=\"tr13\">25<\/td><td class=\"tr13\">13.79%<\/td><\/tr>\n<tr><th>SCA<\/th><td class=\"sca\">147<\/td><td class=\"sca\">37<\/td><td class=\"sca\">75<\/td><td class=\"sca\">33.04%<\/td><\/tr>\n<tr><th>\u4ed6\u306e<br class=\"sponly\">\u67d3\u8272\u4f53<br class=\"sponly\">aneuploidy\/th><td class=\"other\">46<\/td><td class=\"other\">3<\/td><td class=\"other\">29<\/td><td class=\"other\">9.38%<\/td><\/tr>\n<tr><th>CNV<\/th><td class=\"cnv\">109<\/td><td class=\"cnv\">20<\/td><td class=\"cnv\">49<\/td><td class=\"cnv\">28.99%<\/td><\/tr>\n<tr><th>\u5408\u8a08<\/th><td class=\"total\">534<\/td><td class=\"total\">184<\/td><td class=\"total\">219<\/td><td class=\"total\">45.66%<\/td><\/tr>\n<\/tbody><\/table>\n<p class=\"table_comment\">TP true positive, FP false positive, PPV positive rate, SCA sex chromosome anomaly, CNV number difference<\/p>\n<\/section>\n\n<section>\n<p>86.67%, the serious risk of the serological screening group is 71.74%, and the PPV of <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> in increasing the NT group is the highest, 100%. Similarly, the PPV of the increased NT group was also the highest in predicting SCA fetuses. Fetal T18 fetal PPV is 100% for fetal structural abnormalities by B-ultrasound group, increased NT group, and high risk for serological screening, whereas for fetal T13 and CNV prediction; It is worth noting that the PPV of the serological screening group and high risk of fetal structural abnormalities by the B-ultrasound group was the highest, respectively. <\/p>\n<\/section>\n\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Inspection\"><\/span>Inspection<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p><a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> has been widely used for T21, T18, and T13 prenatal screening in the past few years. However, to date, large-scale clinical trials focusing on the efficiency of subchronic mosomal copy number variants (CNVs), which are typically less than 5 Mb in size, have still not been conducted [8, 9] . In addition, there are some concerns regarding clinical performance [10, 11]. Therefore, we hope that this study, which includes 42,910 cases, will provide data support for these questions. <\/p>\n<\/section>\n\n\n<section class=\"note_table table_3\">\n<h3><span class=\"ez-toc-section\" id=\"Table_3_Size_and_number_of_CNVs_and_other_chromosomal_aneuploidies_on_each_chromosome\"><\/span>Table 3 Size and number of CNVs and other chromosomal aneuploidies on each chromosome<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<div class=\"table-sp-scroll\">\n<table>\n\n<thead><tr><th colspan=\"2\">\u67d3\u8272\u4f53<\/th><th>1<\/th><th>2<\/th><th>3<\/th><th>4<\/th><th>5<\/th ><th>6<\/th><th>7<\/th><th>8<\/th><th>9<\/th><th>10<\/th><th>11<\/th>< th>12<\/t h><th>13<\/th><th>14<\/th><th>15<\/th><th>16<\/th><th>17<\/th><th>18<\/th> <th>19<\/th><th>20<\/th><th>21<\/th><th>22<\/th><th>XorY<\/th><th>\u5408\u8a08<\/th><\/ tr>\n<\/thead>\n<tbody>\n<tr><th rowspan=\"3\">CNV<br>\u306e\u9577\u3055<\/th><th class=\"nowrap\">\u2264 5Mb<\/th><td>0<\/td><td>0<\/td><td>0<\/td><td>0<\/td><td>0<\/td><td>0<\/td><td>3<\/td><td>1<\/td><td>0<\/td><td>0<\/td><td>0<\/td><td>\/<\/td><td>2<\/td><td>0<\/td><td>2<\/td><td>2<\/td><td>3<\/td><td>4<\/td><td>\/<\/td><td>0<\/td><td>0<\/td><td>9<\/td><td>11<\/td><td>37<\/td><\/tr>\n<tr><th>5\uff5e<br>10Mb<\/th><td>0<\/td><td>0<\/td><td>0<\/td><td>1<\/td><td>1<\/td><td>1<\/td><td>1<\/td><td>1<\/td><td>0<\/td><td>0<\/td><td>0<\/td><td>\/<\/td><td>2<\/td><td>0<\/td><td>1<\/td><td>0<\/td><td>1<\/td><td>2<\/td><td>\/<\/td><td>1<\/td><td>0<\/td><td>0<\/td><td>5<\/td><td>17<\/td><\/tr>\n<tr><th class=\"nowrap\">&gt;10Mb<\/th><td>1<\/td><td>2<\/td><td>2<\/td><td>2<\/td><td>2<\/td><td>0<\/td><td>6<\/td><td>4<\/td><td>4<\/td><td>3<\/td><td>5<\/td><td>\/<\/td><td>4<\/td><td>2<\/td><td>0<\/td><td>1<\/td><td>0<\/td><td>7<\/td><td>\/<\/td><td>2<\/td><td>1<\/td><td>5<\/td><td>2<\/td><td>55<\/td><\/tr>\n<tr><th rowspan=\"4\">CNV<br>number of<\/th><th><a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a><br>positive<\/th><td>1<\/td><td>2<\/td><td>2<\/td><td>3<\/td><td>3<\/td><td>1<\/td><td>10<\/td><td>6<\/td><td>4<\/td><td>3<\/td><td>5<\/td><td>\/<\/td><td>8<\/td><td>2<\/td><td>3<\/td><td>3<\/td><td>4<\/td><td>13<\/td><td>\/<\/td><td>3<\/td><td>1<\/td><td>14<\/td><td>18<\/td><td>109<\/td><\/tr>\n<tr><th class=\"nowrap\">true positive<\/th><td>1<\/td><td>0<\/td><td>0<\/td><td>1<\/td><td>0<\/td><td>0<\/td><td>1<\/td><td>0<\/td><td>0<\/td><td>0<\/td><td>1<\/td><td>\/<\/td><td>2<\/td><td>1<\/td><td>1<\/td><td>0<\/td><td>0<\/td><td>4<\/td><td>\/<\/td><td>0<\/td><td>1<\/td><td>2<\/td><td>5<\/td><td>20<\/td><\/tr>\n<tr><th class=\"nowrap\">false positive<\/th><td>0<\/td><td>2<\/td><td>0<\/td><td>2<\/td><td>1<\/td><td>1<\/td><td>8<\/td><td>1<\/td><td>1<\/td><td>3<\/td><td>2<\/td><td>\/<\/td><td>3<\/td><td>1<\/td><td>1<\/td><td>3<\/td><td>3<\/td><td>3<\/td><td>\/<\/td><td>0<\/td><td>0<\/td><td>8<\/td><td>6<\/td><td>49<\/td><\/tr>\n<tr><th class=\"nowrap\">unverified<\/th><td>0<\/td><td>0<\/td><td>2<\/td><td>0<\/td><td>2<\/td><td>0<\/td><td>1<\/td><td>5<\/td><td>3<\/td><td>0<\/td><td>2<\/td><td>\/<\/td><td>3<\/td><td>0<\/td><td>1<\/td><td>0<\/td><td>1<\/td><td>6<\/td><td>\/<\/td><td>3<\/td><td>0<\/td><td>4<\/td><td>7<\/td><td>40<\/td><\/tr>\n<tr><th rowspan=\"4\">other<br>chromosome<br>aneuploidy<\/th><th><a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a><br>positive<\/th><td>\/<\/td><td>\/<\/td><td>2<\/td><td>1<\/td><td>1<\/td><td>\/<\/td><td>14<\/td><td>5<\/td><td>2<\/td><td>1<\/td><td>1<\/td><td>1<\/td><td>\/<\/td><td>3<\/td><td>2<\/td><td>4<\/td><td>\/<\/td><td>\/<\/td><td>\/<\/td><td>5<\/td><td><\/td><td>4<\/td><td>\/<\/td><td>46<\/td><\/tr>\n<tr><th class=\"nowrap\">true positive<\/th><td>\/<\/td><td>\/<\/td><td>0<\/td><td>0<\/td><td>1<\/td><td>\/<\/td><td>0<\/td><td>0<\/td><td>0<\/td><td>0<\/td><td>0<\/td><td>0<\/td><td>\/<\/td><td>0<\/td><td>1<\/td><td>0<\/td><td>\/<\/td><td>\/<\/td><td>\/<\/td><td>1<\/td><td>\/<\/td><td>0<\/td><td>\/<\/td><td>3<\/td><\/tr>\n<tr><th class=\"nowrap\">false positive<\/th><td>\/<\/td><td>\/<\/td><td>2<\/td><td>0<\/td><td>0<\/td><td>\/<\/td><td>9<\/td><td>3<\/td><td>1<\/td><td>0<\/td><td>1<\/td><td>1<\/td><td>\/<\/td><td>2<\/td><td>1<\/td><td>4<\/td><td>\/<\/td><td>\/<\/td><td>\/<\/td><td>3<\/td><td>\/<\/td><td>2<\/td><td>\/<\/td><td>29<\/td><\/tr>\n<tr><th class=\"nowrap\">unverified<\/th><td>\/<\/td><td>\/<\/td><td>0<\/td><td>1<\/td><td>0<\/td><td>\/<\/td><td>5<\/td><td>2<\/td><td>1<\/td><td>1<\/td><td>0<\/td><td>0<\/td><td>\/<\/td><td>1<\/td><td>0<\/td><td>0<\/td><td>\/<\/td><td>\/<\/td><td>\/<\/td><td>1<\/td><td>\/<\/td><td>2<\/td><td>0<\/td><td>14<\/td><\/tr>\n<\/tbody>\n<\/table>\n<p class=\"can_slide\">Can slide horizontally<\/p>\n<\/div>\n<\/section>\n\n\n<section class=\"note_table table_4\">\n<h3><span class=\"ez-toc-section\" id=\"Table_4_PPV_according_to_CNV_size\"><\/span>Table 4 PPV according to CNV size<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<table>\n<tbody><tr><th>CNV size<\/th><td>\u22645Mb<\/td><td>5-10Mb<\/td><td>&gt;10Mb<\/td><td>Total <\/td><\/tr>\n<tr><th>NIP positive<\/th><td>37<\/td><td>17<\/td><td>55<\/td><td>109<\/td><\/tr>\n<tr><th>true positive<\/th><td>5<\/td><td>6<\/td><td>9<\/td><td>20<\/td><\/tr>\n<tr><th>false positive<\/th><td>19<\/td><td>6<\/td><td>24<\/td><td>49<\/td><\/tr>\n<tr><th>Not verified<\/th><td>13<\/td><td>5<\/td><td>22<\/td><td>40<\/td><\/tr>\n<tr><th>PPV (%)<\/th><td>20.83<\/td><td>50.00<\/td><td>27.27<\/td><td>28.99<\/td><\/tr>\n<\/tbody><\/table>\n\n<\/section>\n\n<section>\n<p>In this study, <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> was evaluated using positive predictive value (PPV). The PPV for T21 was 79.23%, and for T18 and T13 it was 54.84%, 13.79%, and 33.04%. Additionally, PPVs of other chromosomal aneuploidies and CNVs were also analyzed. The PPV of other chromosomal aneuploidies was 9.38%, and the CNV was 28.99%. In recent studies, the PPV range for T21 was 65\u201394%, T18 was 47\u201385%, and T13 was 12\u201362% [12\u201314]. falls within this range. Interestingly, the PPV of CNV was 28.99%, which was obviously higher than T13. Previous clinical validation studies have reported that the detection performance of specific MMS varies, with positive predictive value (PPV) being slightly low to moderate [9]. <br>\nRecently, more relaxed guidelines have been proposed, allowing routine screening for MMS in young women, where full autosomal full-region deletions are more common than aneuploidies. [15] Based on the results of this retrospective study of more than 42,000 pregnancies, <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> represents a suitable screening method for MMS of central nervous system origin. In this study, the PPV for CNV within 5-10 Mb was the highest (50.00%), and the PPV for CNV below 5 Mb was the lowest (20.83%). The PPV of CNVs&gt;10 Mb (32%) and CNVs&lt;10 Mb (19%) was also low, but reasonable, for potential screening of genome-wide fetal CNVs, according to Liang&#8217;s paper (reference) [9]. This indicates that sufficient sensitivity and specificity of the test is possible. PPV depends not only on the sensitivity and specificity of the test but also on the prevalence of the disease [16]. PPV for CNV <10 Mb is 31% in this study (data not shown in table, PPV = (5 + 6)\/[(5 +)].<\/p>\n<p>6)+19+6)] Much higher than Liang Guanglie&#8217;s paper. Moreover, a previous study reported that the total PPV of CNV was 9.2% [17], and the PPV of the present study was much higher. <br>\nThe PPV for other chromosomal aneuploidies was low at 9.38%, similar to that reported in the paper by Liang (ref.). [9]). The reason is that these aneu-polyploids are not very abundant, and many of them have a high rate of focal placental mosaicism (CPM). <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> is performed using cell-free fetal DNA, and the primary source of cell-fetal DNA in the maternal circulation is apoptosis of placental cells from cell-trophoblasts [18], which are not necessarily representative of the fetus. It is thought that. The situation in which chromosomal abnormalities are found only in the placenta, but not in the fetus, is known as CPM [19], with an observed incidence of approximately 1\u20132% [20]. <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> is a screening test. For pre-counseling for <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a>, selected women should be fully informed about accuracy, reliability, false-positive, and false-negative rates. After counseling, confirmation of all positive findings by invasive prenatal diagnosis is strongly recommended with respect to current <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> guidelines [21]. In addition, all women who were carrying a suspected fetus with a confirmed or potentially pathogenic fetal chromosomal abnormality were scheduled to undergo a genetic counseling session to discuss pregnancy management options. . <br>\nIn addition, although we have further investigated the different PPV of <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> according to pregnancy characteristics, the results in this section require support from more clinical data. Different pregnancy characteristics show different PPVs, with the PPV of <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> being highest at T21 and much lower for other aneuploidies [22]. Older maternal age (usually over 35 years) is a risk factor for T21. Therefore, the PPV of mothers in old age is much higher than in the group without clinical indication. Also, the PPV of high risk in the serological screening group was higher than that in the critical risk group, which is consistent with Yu&#8217;s paper [23]. <\/p>\n<\/section>\n\n\n<section class=\"note_table table_5\">\n<h3><span class=\"ez-toc-section\" id=\"Table_5_Different_PPV_depending_on_pregnancy_characteristics\"><\/span>Table 5 Different PPV depending on pregnancy characteristics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<table>\n<thead>\n<tr>\n<th colspan=\"6\">Clinical characteristics<\/th>\n<\/tr>\n<tr>\n<th>T21 PPV (%)<\/th>\n<th>T18 PPV (%)<\/th>\n<th>T13 PPV (%)<\/th>\n<th>SCAPPV (%)<\/th>\n<th>His Chromosome<br class=\"sponly\">Anomaly PPV (%)<\/th>\n<th>CNV PPV (%)<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<td colspan=\"6\">B-Structural abnormalities of the fetus determined by ultrasound examination<\/td>\n<\/tr>\n<tr>\n<td>0<\/td>\n<td>100<\/td>\n<td>0<\/td>\n<td>0<\/td>\n<td>0<\/td>\n<td>100.00<\/td>\n<\/tr>\n<tr>\n<td colspan=\"6\">NT increase<\/td>\n<\/tr>\n<tr>\n<td>100<\/td>\n<td>100<\/td>\n<td>\/<\/td>\n<td>50.00<\/td>\n<td>0<\/td>\n<td>37.50<\/td>\n<\/tr>\n<tr>\n<td colspan=\"6\">Other a<\/td>\n<\/tr>\n<tr>\n<td>\/<\/td>\n<td>\/<\/td>\n<td>\/<\/td>\n<td>\/<\/td>\n<td>\/<\/td>\n<td>0.00<\/td>\n<\/tr>\n<tr>\n<td colspan=\"6\">High risk for serological screening<\/td>\n<\/tr>\n<tr>\n<td>86.67<\/td>\n<td>100<\/td>\n<td>100<\/td>\n<td>28.57<\/td>\n<td>12.50<\/td>\n<td>11.11<\/td>\n<\/tr>\n<tr>\n<td colspan=\"6\">Serological Screening Serious Risks<\/td>\n<\/tr>\n<tr>\n<td>71.74<\/td>\n<td>33.33<\/td>\n<td>9.09<\/td>\n<td>28.57<\/td>\n<td>0<\/td>\n<td>50.00<\/td>\n<\/tr>\n<tr>\n<td colspan=\"6\">Mother&#8217;s advanced age (\u226735 years)<\/td>\n<\/tr>\n<tr>\n<td>89.29<\/td>\n<td>60.00<\/td>\n<td>9.09<\/td>\n<td>30.77<\/td>\n<td>15.38<\/td>\n<td>5.26<\/td>\n<\/tr>\n<tr>\n<td colspan=\"6\">Not clinically indicated<\/td>\n<\/tr>\n<tr>\n<td>33.33<\/td>\n<td>0<\/td>\n<td>25.00<\/td>\n<td>35.71<\/td>\n<td>0<\/td>\n<td>41.67<\/td>\n<\/tr>\n<tr>\n<td colspan=\"6\">Total<\/td>\n<\/tr>\n<tr>\n<td>79.23<\/td>\n<td>54.84<\/td>\n<td>13.79<\/td>\n<td>33.04<\/td>\n<td>9.09<\/td>\n<td>28.99<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p class=\"table_comment\">&#8216;\/&#8217; is no data<br>\nPatients with contraindications to interventional surgery: reoperative infection, placenta previa, placental hemorrhage, history of unfavorable pregnancy. <\/p>\n<\/section>\n\n\n<section>\n<p>On the other hand, advanced maternal age may not be a risk indicator for T18 and T13. Similarly, unlike aneuploidy, the most common CNVs are not related to maternal age, so older mothers do not have higher PPV values. <br>\nCNVs are increasingly recognized as important contributors to human disease, present in approximately 1.7% of structurally normal pregnancies [24]. Chromosomal microarray analysis (CMA) is a powerful tool for detecting small invisible chromosomal deletions or duplications, and as a first-step diagnostic tool for some pa-thient with well-defined syndromes. Recommended [26, 27]. However, CMA has many limitations. Sampling for CMA requires invasive testing, which is associated with risks such as miscarriage, miscarriage, and intrauterine infection [28][29], or can identify variants of unknown significance. Some women may refuse it. <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a>&#8217;s detection of subchronic mosomal copy number variants (CNVs) has shown good performance in some MMS [30], and in recent years, <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> expanded for MMS has resulted in a significant number of reports. exists [8,9,31]. However, <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> is a screening test, and a clinically valid test is still needed regarding its accurate detection rate and false-positive rate for a large number of clinical samples. <br>\nIn this study, follow-up results are negative. According to the People&#8217;s Republic of China Health Commission guidelines, follow-up started at 12 weeks after delivery. Follow-up should include the subject&#8217;s pregnancy outcome and the health of the newborn. The main follow-up information for newborns is whether the newborn is T21, T18, or T13. Our follow-up began at 3 months of age and strictly followed national guidelines for this study. At follow-up, parents who complain of a newborn with a congenital anomaly should undergo further genetic diagnosis. Furthermore, regarding CNV, although we considered positive results, we hope that this study can provide validity of <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> as a screening test for aneuploidy and CNV. <\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Conclusion\"><\/span>Conclusion<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>In conclusion, this study included a large prospective group of pregnant women with different clinical characteristics. This data is potentially important in demonstrating the utility of using <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> profiling not only for general chromosomal aneuploidies but also for CNVs.  However, this modern method is still in its infancy for CNV. Clinical validation studies with accurate eradication rates and false-positive rates are still needed in clinical practice. <\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Materials_and_methods\"><\/span>Materials and methods<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<h4>Patient<\/h4>\n<p>Pregnant women were collected consecutively. Pregnant women from April 2015 to December 2018 came to Ningbo Women&#8217;s and Children&#8217;s Hospital for prenatal testing. A total of 42,910 pregnant women were recruited. A signed consent form was obtained from each participant before blood collection. Inclusion criteria were (1) gestational age between 12+0 and 26+6, (2) single pregnancy, and (3) body mass index (BMI) <100. Exclusion criteria were: (1) pregnant women with chromosomal abnormalities or abnormalities, (2) multiple pregnancy, (3) pregnant women who underwent stem cell therapy and transplant surgery, (4) received allogeneic blood products within 1 year, and (5) ) received immunotherapy within 4 weeks. <\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Serological_screening_and_ultrasound_examination\"><\/span>Serological screening and ultrasound examination<span class=\"ez-toc-section-end\"><\/span><\/h3>\nA combination of early pregnancy screening from week 11 to week 13+6 was used to detect serological screening tests: AFP, free bHCG, and free E3 concentrations were detected by time-resolved immunofluorescence assay. NT was measured by a trained sonographer according to the Fetal Medicine Foundation protocol [32]. Risk values \u200b\u200bwere calculated by Life Cycle Software (4.0): High risk, T21&gt;1\/300, T18&gt;1\/350; Intermediate risk, T21 1\/300~1\/1000, T18 Increased NT [33] was defined as 1\/350~1\/1000; maternal age (AMA), maternal age \u226535 years [23]; and NT \u22653 mm. <\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Allocation_decision\"><\/span>Allocation decision<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>Maternal peripheral blood (5 ml) was collected into ethyl-enediaminetetraacetic acid (EDTA) tubes at 12+0 to 26+6 weeks of gestational age. Immediately after blood collection, it was stored at 4\u00b0C. Plasma was isolated within 8 hours using a two-step centrifugation protocol as previously described (ref.). [6]). Cell-free DNA extraction, library construction, sequencing, and bioinformatics analysis were performed according to previous studies (ref.). [6]). For high-throughput sequencing of non-fetal DNA fragments, use the JingXin BioelectronSeq 4000 system (CFDA Registration Permit NO.). 20153400309) Semiconductor sequencer. Sequencing reads were filtered and aligned to the human reference genome (hg19). A combination of GC correction method and Z-score testing method was used to identify autosomal aneuploidy in the fetus. Here, each chromosome with an absolute value of Z score greater than 3 was marked with chromosomal aneuploidy or whole autosomal whole region partial deletion\/duplication disease. <\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Karyotype_analysis_and_amniocentesis\"><\/span>Karyotype analysis and amniocentesis<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>Women with positive <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> results were recommended to undergo amniotic fluid karyotyping for further verification. Amniocentesis was performed as routinely described. Karyotype analysis was performed according to the International System for Human Cytogenetic Nomenclature Guidelines [34]. <\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Follow-up_of_negative_cases\"><\/span>Follow-up of negative cases<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>A follow-up survey was conducted for <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> negative cases. According to the guidelines of the Mission of the National Health Commission of the People&#8217;s Republic of China, follow-up was started at 12 weeks after delivery. Follow-up should include the subject&#8217;s pregnancy outcome and the health of the newborn. The main follow-up information for newborns is whether the newborn is T21, T18, or T13. Our follow-up began at 3 months of age and strictly followed national guidelines for this study. At follow-up, parents who complain of a newborn with a congenital anomaly should undergo further genetic diagnosis. Patients who were lost to follow-up were excluded from the analysis. <\/p>\n<\/section>\n\n\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Statistical_analysis\"><\/span>Statistical analysis<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>SPSS 20.0 software was used for statistical analysis. Measured data were expressed as mean \u00b1 standard deviation (x). <br>\n\u00b1SD), adoption rate (%) of count data, positive predictive value = number of true positives\/all positive cases. <\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Abbreviation\"><\/span>Abbreviation<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>cfDNA: Cell-free DNA; CMA: Chromosome microarray analysis; CNV: Copy number variant; MMS: Whole autosomal partial deletion\/duplication disease; <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a>: Non-invasive prenatal testing; NT: Nuchal half Transparent;PPV:Positive Prevalence<\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Thank_you\"><\/span>Thank you<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>Not available. <\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Author_contributions\"><\/span>Author contributions<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>All authors substantially participated in this research and manuscript preparation. YC, QY, and XM collected all clinical data and performed all molecular genetic analyses. WL participated in data analysis and wrote the manuscript. MH was involved in the molecular genetic analysis. WL designed the study, drafted and revised the manuscript. All authors approved the final article. <\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Fund_transfer\"><\/span>Fund transfer<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>Mizue Health Science and Technology Plan (number) 2018KY720\n<\/p><\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Availability_of_data_and_materials\"><\/span>Availability of data and materials<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>The datasets used and\/or analyzed in the current study are available from the corresponding author on reasonable request. <\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Ethical_acknowledgment_and_consent_to_participate\"><\/span>Ethical acknowledgment and consent to participate<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>This study was approved by the Ethics Committee of Ningbo Women&#8217;s and Children&#8217;s Hospital. <\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Consent_to_publication\"><\/span>Consent to publication<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>The authors declare that they have no competing interests and the patient in this case report consented for publication. <\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Contrary_interests\"><\/span>Contrary interests<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>The authors declare that they have no competing interests. <\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Author_details\"><\/span>Author details<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>Ningbo Women&#8217;s Hospital, No.339, China, Ningbo 315010, Haizhou County Ningbo, Kaitong Street, 1 Ningbo Women&#8217;s and Children&#8217;s Hospital, Liuting Street, China, Ningbo 315010. 2CapitalBio\u30fbTechnology Company, China, Beijing 101111 3Beijing CapitalBio Medical Laboratory, Beijing 101111, China.<\/p>\n<p>Acceptance: June 30, 2019 Acceptance: November 15, 2019<\/p>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"References\"><\/span>References<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<ul>\n<li>Lo, Y.M., et al. 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PLoS One. 2014;9(10):e109173.<\/li>\n<li>Hu, H, et al., Clinical experience with non-invasive prenatal chromosomal aneuploidy testing in 190,277 patient specimens. 2016. 16(8): p. -.<\/li>\n<li>Mccullough, R.M.et al., Non-invasive premental chromosomal aneuploidy testing \u2013 Clinical experience: 100,000 clinical specimens 2014. 9(10): p. e109173.<\/li>\n<li>Hu, H., et al., Noninvasive premental testing for chromosomal aneuploidies and subchromosomal microdeleations\/microduplication in a cohort of 8141 Single pregnancy. 2019. 13(1): p. 14.<\/li>\n<li>Liang D, et al. Clinical utility of non-invasive prenatal screening for expanded chromosomal disease syndromes. Genet Med. 2019.<\/li>\n<li>Rose NC, Benn P, Milunsky A. Current controversies in prenatal diagnosis 1: Should <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> routinely include all autosomal partial deletions and duplications? Pregnancy diagnosis. 2016;36(1):10\u20134.<\/li>\n<li>Evans, M.I., et al., Noninvasive prenatal screening or advanced diagnostic testing: caveat emptor. 2016. 215(3): p. 298-305.<\/li>\n<li>Neofytou MC et al. Target capture enrichment assay for non-invasive prenatal testing of large and small subchromosomal deletions and duplications. PLoS One. 2017;12(2):e0171319.<\/li>\n<li>Yaron Y et al. Current status of testing for microdeletion syndromes and rare autosomal trisomies using cell-free DNA technology Obstetrics and Gynecology 2015;126(5):1095\u20139.<\/li>\n<li>Mary E et al. Cell-free DNA analysis for non-invasive testing of trisomy. N Engl J Med. 2015;372:1589\u201397.<\/li>\n<li>Verma, I.C., R. Dua-Puri, and S.J.F. M. Bijarnia-Mahay, ACMG 2016, Update on non-invasive prenatal testing for fetal aneuploidy: Implications for India. 2017. 4(1): p. 1-6.<\/li>\n<li>Lutgendorf, M.A., et al., Noninvasive prefative testing: limitations and open questions. 2014. 16(4): p. 281-285.<\/li>\n<li>Schwartz, S. et al. Clinical experience of non-invasive prenatal testing using cell-free DNA and follow-up with clinical testing for positive autosomal partial deletions in 349 cases. 2018.<\/li>\n<li>Tjoa, M.L., et al., Trophoblastic oxidative stress and release of cell-free fetoplacental DNA. 2006. 169(2): p. 400-404.<\/li>\n<li>J.A.J.O.M.G.P.C.S.i.M.G. Wapner, Trapped placental mosaicism and its impact on confirmation of <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/\">NIPT<\/a> results. 2016. 172(2): p. 118-122.<\/li>\n<li>Grati, F.R., et al., Fetoplacental mosaicism: potential implications for false-positive and false-negative non-invasive prenatal screening results. 2014. 16(8): p. 620.<\/li>\n<li>Gregg, A.R. et al., Noninvasive premental screening fetal aneuploidy, 2016 update: American College of Medical Genetics and Genomics position statement. 2016. 18(10): p. 1056-1065.<\/li>\n<li>Norton ME et al. Cell-free DNA analysis for non-invasive testing of trisomies. 2015;372(17):1589\u201397.<\/li>\n<li>Yu, B, et al., Comprehensive evaluation of the clinical value of prenatal screening for fetal free DNA in maternal blood. 2017. 96(27): p. e7114.<\/li>\n<li>Girirajan, S., C.D. Campbell, and E.E.J.A.R.o.G. Eichler, Human copy number variation and complex genetic diseases. 2011. 45(1): p. 203-226.<\/li>\n<li>Wapner RJ et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012;367(23):2175\u201384.<\/li>\n<li>Miller, D.T., et al., Consensus statement: Chromosomal microarrays are a first-line clinical diagnostic test for individuals with developmental disorders or congenital abnormalities. 2010. 86(5): p. 749-764.<\/li>\n<li>Melanie, M. and H.G.i.M. Louanne, Array-based techniques and recommendations for their use in medical genetics practice for the detection of chromosomal abnormalities. 2010. 12(11): p. 742-745.<\/li>\n<li>Niederstrasser, S.L., et al. Fetal loss after invasive prenatal testing: a comparison of transabdominal chorionic villus sampling, transcervical chorionic sampling, and amniocentesis. 2016. 37(S 01).<\/li>\n\n<li>Tabor A, Alfirevic Z. Update procedure-related risks for prenatal diagnostic techniques. Fetal Diagnosis 2010;27(1):1\u20137.<\/li>\n<li>Srinivasan A et al. Non-invasive detection of fetal subchromosomal abnormalities through deep sequencing of maternal plasma. Am J Hum Genet. 2013;92(2):167\u201376.<\/li>\n<li>Martin K et al. Clinical experience using non-invasive prenatal testing based on single nucleotide polymorphisms for five clinically important autosomal full-region partial deletions. Clin Genet 2018;93(2):293\u2013300.<\/li>\n<li>Nicolaides, K.H., %J American Journal of Obstetrics and Gynecology, Nuchal translucency, and other ultrasound markers of chromosomal abnormalities in early pregnancy. 2004. 191(1): p. 45-67.<\/li>\n<li>Ching-Hua, H., et al., Extended first-trimester screening using multiple sonographic markers and maternal serum biochemistry: a five-year prospective study. 2014. 35(4): p. 296-301.<\/li>\n<li>Gonzalez Garcia, J.R. and J.P.J.B. Mezaespinoza, International system for cytogenetic nomenclature (ISCN). 2006. 108(12): p. 3952.<\/li>\n<\/ul>\n<\/section>\n\n<section>\n<h3><span class=\"ez-toc-section\" id=\"Publishers_Note\"><\/span>Publisher&#8217;s Note<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. <\/p>\n<\/section>\n","protected":false},"excerpt":{"rendered":"Noninvasive prenatal&#8230;\n <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt-cohort-study\/?lang=en\">\u7d9a\u304d\u3092\u8aad\u3080<\/a>","protected":false},"author":1,"featured_media":24299,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[97],"tags":[],"class_list":["post-85790","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts\/85790","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/comments?post=85790"}],"version-history":[{"count":3,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts\/85790\/revisions"}],"predecessor-version":[{"id":109603,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts\/85790\/revisions\/109603"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/media\/24299"}],"wp:attachment":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/media?parent=85790"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/categories?post=85790"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/tags?post=85790"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}