Cell-free fetal nucleic acids as prenatal biomarkers

Cell-free fetal nucleic acids in maternal plasma or serum have become important tools in the pursuance of new methods for non-invasive prenatal diagnosis, such as the determination of fetal blood groups and fetal gender. During these pioneering explorations, elevations in the concentration of these new-found biological analytes were noted in several pregnancy-related disorders, including preterm labor, pre-eclampsia and malimplantation. As these elevations appeared to occur before onset of clinical symptoms, it was proposed that such analyses might assist in screening for at-risk pregnancies. A major problem with these early studies is that they relied on the quantitation of Y-chromosome-specific gene sequences, and as such could be applied only in those cases where the fetus was male. Recent developments that might permit gender-independent analysis include epigenetic markers, as well as the analysis of cell-free placentally derived mRNA species.

This article focuses specifically on prognostic markers, which enable at-risk pregnancies to be identified, allowing the modification of pregnancy management and in turn improvement of pregnancy outcome. The authors also provide their opinion on the progress and future challenges that lie ahead.

Accurate quantification of fetal nucleic acids and the specificity of these elevations for particular disorders remain controversial issues. Regarding the multifactorial etiology of some pregnancy disorders, the use of fetal nucleic acids as prenatal markers is restricted to well-defined high-risk groups.