Fetal nucleated cells in maternal peripheral blood: frequency and relationship to gestational age

Abstract

To determine the frequency of fetal nucleated cells in maternal peripheral blood during different stages of pregnancy, 50 primigravidas were investigated by determining the frequency of cells with the Y chromosome using fluorescence in situ hybridization (FISH) of Y-specific repetitive sequences of the DYZ1 family. Polymerase chain reaction (PCR) amplifying the same part of the DYZ1 used as the probe in FISH and a single-copy Y-specific fragment was also carried out for genomic DNA from the same samples. Cells with the hybridization signal were detected by FISH at and after 15 weeks of pregnancy in all pregnant women who gave birth to boys. The ratio of cells with the signal to those without the signal ranged from 1 in 144,000 to 1 in 4,000 with a tendency to increase as the pregnancy advanced. The frequency of fetal cells estimated by the PCR experiments was significantly and positively correlated with that found by FISH. The present study suggests that fetal nucleated cells increase in maternal peripheral blood with advancing gestation, from less than 1 in 100,000 nucleated cells in the first trimester to around 1 in 10,000 at term. These frequencies were much lower than those reported by cytological methods.

Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood

“…Noninvasive prenatal diagnosis of aneuploidy has been a challenging problem because fetal DNA constitutes a small percentage of total DNA in maternal blood (13), and intact fetal cells are even rarer (6,7,9,31,32). We showed in this study the successful development of a truly universal, polymorphism-independent noninvasive test for fetal aneuploidy.…”

An alternatively spliced form of HLA-G mRNA in human trophoblasts and evidence for the presence of HLA-G transcript in adult lymphocytes.

“…Thus, HLA-G may protect the fetal trophoblasts from NK cell killing and confer immunological tolerance of fetus vs. mother. Another intriguing immunological problem concerns the finding that human fetal cells can cross the placental barrier and transfer into maternal circulation at about 8 weeks of gestation (29,30) and may persist up to 8 months after delivery (31). It is unclear in which manner the fetal cells escape the mother's immunological control and possible cytotoxic reactions.…”

FISH Analysis of All Fetal Nucleated Cells in Maternal Whole Blood: Improved Specificity by the Use of Two Y-chromosome Probes

“…Evidence that the latter approach may be feasible was described in nonblinded studies for the first time by Hamada et al (1993) and more recently by Krabchi et al (2001). Hamada et al (1993) published parallel investigations by FISH and polymerase chain reaction (PCR) in 50 pregnancies in which both methods used repetitive and single-copy sequences specific for the Y-chromosome. Analyzing ‫ف‬ 100,000 nucleated cells per maternal blood sample, these investigators reported an overall sensitivity of 82.8% for Y-chromosome-specific FISH as well as increasing fetal cell numbers during pregnancy.…”