Maternal origin of nucleated erythrocytes in peripheral venous blood of pregnant women

Abstract

We studied the origin of nucleated red blood cells (NRBC) in peripheral venous blood samples from 40 pregnant women carrying a male fetus, using a technique that allows direct chromosomal analysis by in situ hybridisation on immunologically and morphologically classified cells. Samples from ten nulligravid women were studied as controls. NRBC were enriched by negative magnetic activated cell sorting (miniMACS) using anti-CD45 monoclonal antibody. NRBC were detected by alkaline phosphatase anti-alkaline phosphatase immunostaining using a monoclonal anti-glycophorin A antibody. The origin of the NRBC was determined by fluorescence in situ hybridisation using X and Y specific probes. NRBC were found in 37 of the 40 pregnant women at a range of 1 to 230 per 20 ml of venous blood and in 6 of the 10 controls at a range of 1 to 3 per 20 ml of venous blood. All NRBC detected in the pregnant women were evidently of maternal origin, and in the pregnant women the number of NRBC was significantly higher (P < 0.05) than in the controls. Pregnancy per se seems to induce the appearance of maternal NRBC in the circulation, and it cannot therefore be assumed that NRBC isolated from the maternal blood are of fetal origin on the basis of morphology alone. Discrimination of fetal NRBC must occur for prenatal diagnosis of fetal genetic disorders.

Fetal Gender Determination and BclI Polymorphism Using Nucleated Erythrocytes in Maternal Blood

“…Combining these results, we could conclude that these three cells were of maternal origin. This finding also gives evidence that NRBCs in maternal blood are of both fetal and maternal origin, and it is comparable to those of previous studies (Ganshirt et al 1994;Slunga-Tallberg et al 1995von Eggeling et al 1997;Holzgreve et al 1998;Troeger et al 1999).…”

“…The problem is that NRBCs in maternal peripheral blood are of both fetal and maternal origin (Ganshirt et al 1994;Slunga-Tallberg et al 1995von Eggeling et al 1997;Holzgreve et al 1998;Troeger et al 1999). However, despite the fact that nucleated erythrocytes in maternal peripheral blood are of fetal and maternal origin, many researchers have claimed that they can diagnose various disorders using NRBCs in maternal peripheral blood, such as hemoglobinopathies (Di Naro et al 2000), Rhesus type, and Duchenne muscular dystrophy (Sekizawa et al 1996a,b).…”

Improved Specificity of NRBC Detection in Chorionic Villus Sample Supernatant Fluids Using Anti-Zeta and Anti-Epsilon Monoclonal Antibodies

“…While use of Abs against HBF Á-chain has improved recognition of NRBCs, it is not a 100% specific marker for fetal cells, since it is known that women during pregnancy may produce and release in the circulation adult Hb F Á-positive NRBCs [2][3][4]. In our study we identified 5 cases in which the fetus was shown correctly by FISH to be male, but NRBCs with two X signals were also detected in the CVS supernatant [1].…”

Enrichment, identification and analysis of fetal cells from maternal blood: evaluation of a prenatal diagnosis system

“…Analysis of this haemoglobin chain revealed it was most probably maternal in origin. Also Oosterwijk et al (1998b) and Slunga-Tallberg et al (1995) found that a considerable proportion of HbF-positive NRBCs in the blood of pregnant women is maternal.…”