Fetal cells in the maternal circulation: Feasibility for prenatal diagnosis

With the advent of sensitive molecular genetic analytic techniques, the existence of fetal nucleated cells in maternal blood samples has been conclusively demonstrated. Quantitative PCR studies performed on maternal whole blood and plasma/serum samples have shown that in most pregnancies, fetal cells are rare in number. A larger feto-maternal transfusion occurs when the fetus is aneuploid, or when preeclampsia develops. Detection of aneuploidy is likely to be facilitated by the increased number of fetal cells detectable in the mother, as well as the fact that blood cells from aneuploid fetuses are immature for gestational age and express many antigens at higher density than normal fetal or immature maternal cells. The major strategies being used to detect fetal cells include enrichment, cell culture, and improved recognition through automated microscope scanning. At present, almost all fetal aneuploidies have been diagnosed in maternal blood using FISH. Many single gene mutations have also been demonstrated. Conditions in which the mother is also a carrier of a mutant gene can be addressed by micromanipulation and single-cell PCR. Recent data regarding the postpartum development of fetal cell microchimaerism in the mother and its possible relationship to subsequent onset of 'autoimmune' disorders may enhance our understanding of the fetus as an allograft and engender a new appreciation of the biology of human pregnancy.