Noninvasive Prenatal Test by Cell-Free Fetal DNA in Maternal Plasma: Current Progress and Prospective Clinical Applications

Context: Prenatal testing aims to identify fetal chromosomal and genetic disorders prior to delivery. Current invasive procedures such as amniocentesis and chorionic villus sampling (CVS) pose a risk to mother and fetus and such diagnostic procedures are available only to high-risk pregnancies, which limits aneuploidy detection rate. The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made noninvasive prenatal testing (NIPT) possible. This review seeks to highlight the necessity of investing in NIPT and briefly summarizes the technical aspects of the NIPT and application of this method in clinical practice.Evidence Acquisition: PubMed, OVID, SCOPUS, and the Cochrane database were searched for relevant articles published between 1995 and 2014, using appropriate keywords including prenatal screening, noninvasive testing, prenatal diagnosis, cell free fetal DNA, maternal circulation, chromosomal aneuploidies, trisomy, and sex determination. Results were restricted to systematic reviews, randomized clinical trials, meta-analysis, and observational studies. The importance of prenatal diagnosis and risks associated with current invasive techniques makes NIPT research morally and commercially beneficial. The outstanding advantages of NIPT over current prenatal diagnosis techniques include increasing detection rate, enabling earlier diagnosis, and eliminating iatrogenic fetal loss and risk to the mother due to invasive procedures. At present, two major techniques for isolating cffDNA, namely digital PCR and massively parallel sequencing (MPS), have enabled the successful implementation of NIPT into clinical practice such as fetal sex determination, RhD genotyping, and fetal chromosomal aneuploidy detection. The advent of new NIPT using cffDNA has been regarded as a revolution in prenatal testing and has attracted significant commercial interest in the field. It is not overoptimistic to predict that NIPT will supplement or replace existing screening and diagnostic tools.