Noninvasive prenatal diagnosis: current practice and future perspectives

Abstract

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.