Current knowledge about fetal blood cells in the maternal circulation.

The aim of this review is to summarize the current status and future prospects of noninvasive prenatal genetic analysis by the isolation of fetal cells from the maternal circulation. The presence of fetal cells in maternal blood is no longer considered controversial. A variety of cell separation methods recover fetal cells from maternal blood; these differ in cost-effectiveness and required expertise. Fetal cell types that are useful for prenatal diagnosis are terminally differentiated and are unlikely to persist post-partum. Most investigators are isolating trophoblast sprouts, nucleated erythrocytes, or both from maternal blood. Advances in the understanding of cell surface and cytoplasmic protein expression have translated into better and more specific fetal cell identification. Fetal cells, once identified, are being screened for the presence of aneuploidy using chromosome-specific probes on interphase nuclei. Significant progress in single gene and single cell analysis has expanded the diagnostic possibilities for noninvasive fetal testing. Although fetal cells are generally rare in maternal blood samples, they appear to be more common when the fetus has trisomy 21. This is beneficial for clinical diagnosis. Furthermore, a large fetomaternal transfusion occurs at the time of labor and delivery in all pregnant women. This may establish fetal cell microchimerism in the mother, which may be implicated in the subsequent development of diseases such as scleroderma that are more common in women. The study of fetal cells in maternal blood, while technically challenging, provides a unique opportunity to explore the immunobiology of pregnancy.