Fetal cells in the maternal circulation: feasibility for prenatal diagnosis

Bianchi, Diana W.

doi:10.1046/j.1365-2141.1999.01383.x

Cited by 176 publications

(125 citation statements)

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“…1 There are currently 3 steps: enrichment of fetal cells in maternal blood, identification of fetal cells among background maternal cells, and diagnosis using fluorescence in situ hybridization (FISH) or single-cell techniques. Antibody directed against the ␥ chain of fetal hemoglobin is commonly used for both the fetal cell enrichment 2,3 and identification 4 steps.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous fetal cell identification and diagnosis by epsilon-globin chain immunophenotyping and chromosomal fluorescence in situ hybridization

Choolani

O'Donnell

Campagnoli

et al. 2001

Blood

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Isolating fetal erythroblasts from maternal blood offers a promising noninvasive alternative for prenatal diagnosis. The current immunoenzymatic methods of identifying fetal cells from background maternal cells postenrichment by labeling ␥-globin are problematic. They are nonspecific because maternal cells may produce ␥-globin, give poor hybridization efficiencies with chromosomal fluorescence in situ hybridization (FISH), and do not permit simultaneous visualization of the fetal cell identifier and the FISH signal. We describe a novel technique that allows simultaneous visualization of fetal erythroblast morphology, chromosomal FISH, and ⑀-globin labeled with AMCA (7-amino-4-methylcoumarin-3-acetic acid).AMCA was chosen as the fluorescent label to circumvent the problem of heme autofluorescence because the mean difference in relative fluorescence intensity between fetal erythroblasts stained positive for antiglobin antibody and autofluorescence of unstained cells was greater with AMCA (mean 43.2; 95% confidence interval [CI], 34.6-51.9; SD ‫؍‬ 14.0) as the reporting label compared with fluorescein isothiocyanate (mean 24.2; 95% CI, 16.4-31.9; SD ‫؍‬ 12.4) or phycoerythrin (mean 9.8; 95% CI, 4.8-14.8; SD ‫؍‬ 8.0). Median FISH hybridization efficiency was 97%, comparable to the 98% (n ‫؍‬ 5 paired samples) using Carnoy fixative. One ⑀-positive fetal erythroblast was identified among 10 5 maternal nucleated cells in 6 paired mixture experiments of fetal erythroblasts in maternal blood (P < .001). Male ⑀-positive fetal erythroblasts were clearly distinguishable from adult female ⑀-negative erythroblasts, with no false positives (n ‫؍‬ 1000). The frequency of fetal erythroblasts expressing ⑀-globin declines linearly from 7 to 14 weeks' gestation (y ‫؍‬ ؊15.8 ؋ ؉ 230.8; R 2 ‫؍‬ 0.8; P < .001). We describe a rapid and accurate method to detect simultaneously fetal erythroblast morphology, intracytoplasmic ⑀-globin, and nuclear FISH. IntroductionIsolating fetal nucleated red blood cells (NRBCs) from maternal blood should allow first trimester noninvasive prenatal diagnosis of aneuploidy and monogenic disorders. 1 There are currently 3 steps: enrichment of fetal cells in maternal blood, identification of fetal cells among background maternal cells, and diagnosis using fluorescence in situ hybridization (FISH) or single-cell techniques. Antibody directed against the ␥ chain of fetal hemoglobin is commonly used for both the fetal cell enrichment 2,3 and identification 4 steps. There may be a case for using ␥-globin for sorting, favoring yield over purity, but it is not nearly specific enough for accurate fetal erythroblast identification because of increased maternal fetal hemoglobin production in pregnancy 5 and ␤ thalassemia. 6,7 In contrast, ⑀-or -globin chains appear specific for fetal cells in chorionic villus supernatants 7 but have not been tested in maternal blood. Whereas -globin is occasionally produced in adults with ␣ thalassemia, 8 ⑀-globin has not been found in adult peripheral blood, 9 making it the prefer...

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Section: Introductionmentioning

confidence: 99%

Simultaneous fetal cell identification and diagnosis by epsilon-globin chain immunophenotyping and chromosomal fluorescence in situ hybridization

Choolani

O'Donnell

Campagnoli

et al. 2001

Blood

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“…Due to the uncertain results of ultrasound before 13 weeks of gestation, assessment of fetal sex by this technique is usually done in the second trimester of pregnancy. Recovery of transcervical cells [22] and isolation of fetal cells from maternal blood [23] have also has been reported for the detection of fetal gender, but problems due to lack of sensitivity or specificity; frequent method failure rates and high cost make them unsuited to routine application. The detection of cell-ffDNA in maternal blood in 1997 has opened up new possibilities for noninvasive prenatal diagnosis and created an important field of study in prenatal genetic diagnosis, including fetal sex determination for couples at risk of X-linked diseases such as Haemophilia, single-gene disorders of paternal origin, and fetal RhD status in RhD -negative women.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of an Improved Non- invasive Fetal Sex Determination in Haemophilia A Patients

Mokarizadeh

Mesbah‐Namin

2015

JCDR

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Background: Haemophilia A (HA) is the most severe sex-linked bleeding disorder that is characterized with non-controlled and often threatening Haemorrhage. Routine fetal sex determination in early pregnancy with Haemophilia is based on invasive procedures that can be dangerous to the mother and fetus.Aim: The goal of this study is to present an improved assay for the non-invasive fetal sex determination using a Real-Time duplex PCR on the free fetal DNA (ffDNA) obtained from the maternal serum of the HA carriers.

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“…Several types of fetal cells, including progenitor cells have been detected in the maternal peripheral blood and organs during gestation (Walknowska et al 1969;Covone et al 1984;Bianchi 1999;Osada et al 2001); however, it was not known where these fetal cells were located and how these cells functioned in the maternal body. It was recently reported that the Y-chromosome DNA of fetus origin (maternal-fetal microchimerism) was found in the peripheral blood of female patients with lupus nephritis (Mosca et al 2003) and in the salivary glands and lungs of female patients with Sjögren's syndrome (Kuroki et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…, trophoblasts (Covone et al 1984), leukocytes (Bianchi 1999), and hematopoietic progenitor cells (Osada et al 2001), have been detected in the maternal peripheral blood during gestation and have been used in the noninvasive prenatal diagnosis of congenital anomalies (Bianchi et al 1990). In fact, fetal cells can persist in the maternal circulation long after birth.…”

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confidence: 99%