Noninvasive prenatal diagnosis: current practice and future perspectives

Purpose of review To review recent developments in the noninvasive determination of fetal genetic loci via the use of fetal cells or cell-free nucleic acids in maternal blood, and provide an overview of the possibilities for future clinical applications. Recent findings Noninvasive prenatal fetal sex or Rhesus D status determination via the analysis of cell-free fetal DNA is now offered by a number of European centres. The detection of fetal loci not completely disparate from maternal ones, such as point mutations, however, is more complex due to the preponderance of maternal cell-free DNA. Promising approaches to overcome this drawback include specialized PCR protocols employing peptide-nucleic acid clamps, mass spectrometry or the enrichment of fetal cell-free DNA sequences by size-fractionation. The discovery of cell-free fetal mRNA has opened up the exciting possibility of noninvasive detection of Down's syndrome, as well as examination of fetal gene expression profiles. Summary The noninvasive determination of Mendelian disorders such as thalassemia or cystic fibrosis, and Down's syndrome may soon become a clinical reality. Noninvasive fetal profiling technologies could lead to the development of a new generation of highly specific tools for the detection of pregnancies at risk for preeclampsia or preterm labour.