Prenatal diagnosis of fetal chromosome abnormalities currently relies on invasive testing, by amniocentesis or chorionic villous sampling in women considered to be at high risk. Evaluation of high-risk pregnancies includes a positive result for a screening test. Because of the uncertainties of screening and invasive procedure related risk, as well as miscarriage and maternal medical complications, there is a considerable interest in developing noninvasive alternatives for obtaining genetic information of the gestating fetus. One such alternatives involves recovery of fetal cells from maternal circulation.
The presence of fetal cells was, at first, probably reported in 1893, when fetal trophoblasts were found in the lung of a pregnant woman affected by eclampsia, a severe disease of the pregnancy. In 1969, Y-chromatin was reported in blood cells from women carrying male fetuses. Ten years later, fetal leukocytes were detected and, in 1990, fetal nucleated red blood cells were recovered. In summary, throughout the years various types of fetal cells have been separated from maternal blood: trophoblasts, lymphocytes, granulocytes, and nucleated red blood cells. Among those, nucleated red blood cells, or erythroblasts, appear to have the greatest potential of being used during pregnancy for prenatal genetic analysis of both chromosome anomalies and single gene disorders.
Because fetal cells are rare in maternal blood in respect to maternal cells, sophisticated analyses for cell separation and detection are needed to isolate and to evaluate them. However, although rare, these cells can be obtained as early as 6-8 weeks gestation without any risk to mother or fetus. Genetic analysis of the identified fetal cell has relied primarily on two techniques, fluorescent in site hybridization (FISH) for chromosome specific probes, and polymerize chain reaction (PER) to amplify uniquely fetal gene sequences. Evidence of diagnosis of fetal genetic anomalies includes, thus far, trisomy 13, 18 and 21, triploidy, sickle cell anemia, thalassemia, cystic fibrosis, and Duchenne muscular dystrophy.
When the gestation is complicated by fetal trisomy 21, the observed number of erythroblasts is, in average, higher then the expected for a normal pregnancy. This further finding, allows consideration of the number of fetal cells in maternal blood as a marker for aneuploidies to be used as a primary or secondary screen, combined in a sequential algorithm with other non invasive tests such as biochemical or ultrasonographic screening. Although, no large screenings project have been performed so far, evidences suggest that this application of fetal cells can open a new route for screening tests.
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