Diagnostic Value of Fetal Nucleic Acid in Maternal Plasma

Prenatal diagnosis is now part of established obstetric practice in many countries. However, conventional methods of obtaining fetal tissues for genetic analysis, including amniocentesis and chorionic villus sampling, are invasive and constitute a finite risk to the unborn fetus. It has been a long-sought goal in human genetics to develop methods of obtaining fetal genetic materials for analysis.The discovery of cell-free fetal DNA in maternal plasma in 1997 has opened up new possibilities for noninvasive prenatal diagnosis. Circulating fetal DNA molecules have been detected in maternal plasma from the first trimester onwards and can be robustly detected using a variety of molecular methods. This approach has been used for the prenatal investigation of sex-linked diseases, fetal RhD status, and prenatal exclusion of ß-thalassemia major. Recently, fetal RNA has also been found in maternal plasma. Such fetal RNA has been shown to originate from the placenta and to be remarkably stable. The use of microarray-based approaches has made it feasible to rapidly generate new circulating RNA markers. It is hoped that further developments in this field will make the routine and widespread practice of noninvasive nucleic acid–based prenatal diagnosis for common pregnancy-associated disorders feasible in the near future.