Non-invasive Prenatal Diagnosis of Chromosomal Aneuploidies and Microdeletion Syndrome Using Fetal Nucleated Red Blood Cells Isolated by Nanostructure Microchips

Feng, Chun; He, Zhaobo; Cai, Bo; Peng, Jianhong; Song, Junjie; Yu, Xuechen; Sun, Yue; Yuan, Jing; Zhao, Xingzhong; Zhang, Yuanzhen

doi:10.7150/thno.21979

Cited by 37 publications

(50 citation statements)

References 38 publications

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“…An average of 53 fnRBCs per mL were captured from these maternal blood samples. The number of cells peaked around 17th–18th weeks of gestation, which was consistent with previous reports .…”

Section: Resultssupporting

confidence: 92%

“…Therefore, fnRBCs have been considered to have the greatest potential among cells for noninvasive prenatal diagnosis. This type of cell has been used prenatally to noninvasively diagnose chromosomal aneuploidy and microdeletion syndrome of the fetus .…”

Section: Introductionmentioning

confidence: 99%

“…As Fig. shows, silica microbeads (SiO 2 MBs) of 30 µm in diameter and 2 g/mL in density were first wholly modified with streptavidin and then conjugated with biotinylated anti‐CD147 antibody to specifically capture fnRBCs from maternal blood. After cell capture, Percoll separation solution (1.13 g/mL) was utilized as a density‐selective sedimentation to purify the cell‐attached MBs (>1.13 g/mL) from white blood cells (WBCs, 1.07–1.09 g/mL).…”

Section: Introductionmentioning

confidence: 99%

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Silica microbeads capture fetal nucleated red blood cells for noninvasive prenatal testing of fetal ABO genotype

et al. 2020

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Silica microbeads capture fetal nucleated red blood cells for noninvasive prenatal testing of fetal ABO genotypeABO hemolytic disease of the newborn (ABO-HDN), which may cause neonatal jaundice and polycythemia, or even stillbirth or neonatal death, is widespread in China. Prenatal testing for the fetal ABO blood group can reduce unnecessary concerns or ensure prompt treatment. Herein, we presented a method to employ high-density silica microbeads (SiO 2 MBs) for capturing fetal nucleated red blood cells (fnRBCs) in maternal peripheral blood, and we detected the ABO genotype of the fetus using these captured cells. We evaluated 52 patients using the SiO 2 MBs. Among 26 pregnant women with type O blood, 8 (30.8%) of the fetuses had type A blood, 5 (19.2%) had type B blood, and 13 (50%) had type O blood. SRY genes were detected in all 27 male fetuses. This study represents a simple and effective method for noninvasive prenatal detection of the fetal ABO genotype. We believe that this method has great potential for noninvasive prenatal testing of the fetal Rh blood group and other fetal diseases as well.Abbreviations: ABO-HDN, ABO hemolytic disease of the newborn; CTCs, circulating tumor cells; fnRBCs, Fetal nucleated red blood cells; PCR-SSP, PCR with sequence specific primer; SiO 2 MBs, silica microbeads * These authors contributed equally.

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Silica microbeads capture fetal nucleated red blood cells for noninvasive prenatal testing of fetal ABO genotype

et al. 2020

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“…However, using circulating fetal cells for prenatal diagnosis compared with cffDNA allows for whole genome analysis on DNA from pure fetal cells without maternal contamination 7‐9 . Several different types of circulating fetal cells have been identified and targeted for prenatal diagnosis, including lymphoid progenitor cells, nucleated red blood cells and fEVTs 10‐14 …”

Section: Introductionmentioning

confidence: 99%

Do fetal extravillous trophoblasts circulate in maternal blood postpartum?

Looij

Singh²,

Hatt³

et al. 2020

Acta Obstet Gynecol Scand

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractIntroduction: Circulating fetal extravillous trophoblasts may offer a superior alternative to cell-free fetal DNA for noninvasive prenatal testing. Cells of fetal origin are a pure source of fetal genome; hence, unlike the cell-free noninvasive prenatal test, the fetal cell-based noninvasive prenatal test is not expected to be affected by maternal DNA. However, circulating fetal cells from previous pregnancies may lead to confounding results. Material and methods:To study whether fetal trophoblast cells persist in maternal circulation postpartum, blood samples were collected from 11 women who had given birth to a boy, with blood sampling at 1-3 days (W0), 4-5 weeks (W4-5), around 8 weeks (W8) and around 12 weeks (W12) postpartum. The existence of fetal extravillous trophoblasts was verified either by X and Y chromosome fluorescence in situ hybridization analysis or by short tandem repeat analysis. To exclude technological bias in isolating fetal cells, blood samples were also collected from 10 pregnant women between a gestational age of 10 and 14 weeks, the optimal time frame for cell-based noninvasive prenatal test sampling. All the samples were processed according to protocols established by ARCEDI Biotech for fetal extravillous trophoblast enrichment and isolation.Results: Fetal extravillous trophoblasts were found in all the 10 samples from pregnant women between a gestational age of 10 and 14 weeks. However, only 4 of 11 blood samples taken from women at 1-3 days postpartum rendered fetal extravillous trophoblasts, and only 2 of 11 samples rendered fetal extravillous trophoblasts at 4 weeks postpartum. Conclusions:In this preliminary dataset on few pregnancies, none of the samples rendered any fetal cells at or after 8 weeks postpartum, showing that cell-based noninvasive prenatal testing based on fetal extravillous trophoblasts is unlikely to be influenced by circulating cells from previous pregnancies. K E Y W O R D S chorionic villi sampling, fetal cells, fetal extravillous trophoblasts, noninvasive prenatal testing, prenatal diagnosis S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section.

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“…As expected, each of these conditions has been associated with increased NRBCs in the newborn 9 . The other objective is to screen and extract fNRBCs from maternal peripheral blood for non-invasive prenatal diagnosis (NIPD) 10–12 . The choice of fNRBCs as ideal target cells is based on the following parameters 13,14 : (1) presence of intact nuclei containing the complete fetal genome in fNRBCs, which is a prerequisite for prenatal analysis; (2) limited life span of fNRBCs in the maternal circulation, which can be differentiated morphologically from maternal cells; and (3) presence of distinct cell markers, such as epsilon hemoglobin transferrin receptor (CD71) 15 , thrombospondin receptor (CD36), and glycophorin A (GPA) in fNRBCs that enable isolation of these rare cells from large volumes of maternal blood.…”

Section: Introductionmentioning

confidence: 99%

Deep learning-based adaptive detection of fetal nucleated red blood cells

Sun

Wang

Zhao

et al. 2020

Preprint

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15Aim: this study, we established an artificial intelligence system for rapid 16 identification of fetal nucleated red blood cells (fNRBCs). 17Method: Density gradient centrifugation and magnetic-activated cell sorting were 18 used for the separation of fNRBCs from umbilical cord blood. The cell block 19 technique was used for fixation. We proposed a novel preprocessing method based on 20 imaging characteristics of fNRBCs for region of interest (ROI) extraction, which 21 automatically segmented individual cells in peripheral blood cell smears. The 22 discriminant information from ROIs was encoded into a feature vector and 23 pathological diagnosis were provided by the prediction network. 24Results: Four umbilical cord blood samples were collected and validated based on a 25 large dataset containing 260 samples. Finally, the dataset was classified into 3,720 and 26 1,040 slides for training and testing, respectively. In the test set, classifier obtained 27 98.5% accuracy and 96.5% sensitivity. 28Conclusion: Therefore, this study offers an effective and accurate method for 29 fNRBCs preservation and identification. 30 Keywords: fetal nucleated red blood cells, cell-block, deep learning, non-invasive 31 prenatal diagnosis 32 Introduction 33The clinical application of fNRBCs during pregnancy could be classified into two 34 main categories 1,2 . One is the prognosis of possible diseases in pregnant women by 35 counting fNRBCs in umbilical cord blood. Chronic tissue hypoxia results in increased 36 levels of erythropoietin, which, in turn, leads to stimulation of erythropoiesis and 37 increased numbers of circulating nucleated red blood cells (NRBCs) 1,3-5 . Increased 38 umbilical cord levels of erythropoietin have been reported in pregnancies complicated 39 by intrauterine growth restriction, maternal hypertension, preeclampsia, maternal 40 smoking, Rh isoimmunization, and maternal diabetes 5-8 . As expected, each of these 41 conditions has been associated with increased NRBCs in the newborn 9 . The other 42 objective is to screen and extract fNRBCs from maternal peripheral blood for 43 non-invasive prenatal diagnosis (NIPD) 10-12 . The choice of fNRBCs as ideal target 44 cells is based on the following parameters 13,14 : (1) presence of intact nuclei containing 45 the complete fetal genome in fNRBCs, which is a prerequisite for prenatal analysis; (2) 46 limited life span of fNRBCs in the maternal circulation, which can be differentiated 47 55 cells) 16,17 . Several fNRBC enrichment methods based on different principles have 56 been reported, such as density gradient centrifugation (DGC) 13,18 , 57 fluorescence-activated cell sorting (FACS) 19 , and magnetic-activated cell sorting 58 (MACS) 20 , dielectrophoresis, and microfluidics based technologies 21,22 . Nevertheless, 59 long-term preservation of samples and rapid identification of target cells (fNRBCs) 60 still present considerable challenges. 61 Since the identification of fNRBCs in large number of cell block slices represent a 62 huge manual burden on p...

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Non-invasive Prenatal Diagnosis of Chromosomal Aneuploidies and Microdeletion Syndrome Using Fetal Nucleated Red Blood Cells Isolated by Nanostructure Microchips

Cited by 37 publications

References 38 publications

Silica microbeads capture fetal nucleated red blood cells for noninvasive prenatal testing of fetal ABO genotype

Silica microbeads capture fetal nucleated red blood cells for noninvasive prenatal testing of fetal ABO genotype

Do fetal extravillous trophoblasts circulate in maternal blood postpartum?

Deep learning-based adaptive detection of fetal nucleated red blood cells

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