Isolation of fetal nucleated red blood cells from maternal blood in normal and aneuploid pregnancies.

Abstract

Fetal nucleated red blood cells (NRBC) have been widely reported in maternal blood during pregnancy. However, there is no consensus with regard to their presence in all pregnancies. Therefore, the usefulness of developing a fetal NRBC-based noninvasive method suitable for clinical prenatal diagnosis remains uncertain. Fluorescence in situ hybridization (FISH) method was used to evaluate the ability of one of our own monoclonal antibodies (mAb), 2B7.4, to isolate fetal NRBC from maternal blood by magnetic activated cell sorting (MACS). Our mAb was able to isolate from 25 to 822 NRBC from all of the 45 maternal blood samples included in this study. A correct diagnosis was achieved in 21 out of 24 pregnancies carrying trisomic fetuses (87.5%), with a fetal/maternal NRBC frequency of 8.4%. In contrast, a significantly lower percentage of fetal NRBC (0.2%) was observed in 22% of pregnancies carrying a chromosomally normal male fetus, that were correctly predicted. In conclusion, using 2B7.4 mAb we succeeded in isolating NRBC from the maternal blood samples, but most of the isolated cells were maternal in origin. Nevertheless, a higher number of fetal NRBC was found in the peripheral blood of pregnant women carrying aneuploid fetuses, which could allow development of a screening method for prenatal diagnosis of fetal aneuploidies.