ABSTRACT
Since all prenatal invasive procedures, such as amniocentesis and chorionic villus sampling carry a small risk for the pregnant woman and a risk to induce the loss of a pregnancy of up to 1%, there have been efforts now for at least a quarter of a century to develop a noninvasive method from the blood of pregnant women. First there was a considerable effort to isolate fetal cells from maternal circulation, and these techniques were carefully evaluated in a NIH-sponsored study of a few US American centers and ours in Basel/Switzerland. It turned out; however, that interphase fluorescence to identify fetal aneuploidies from these isolated cells was not reliable enough for clinical use. The breakthrough came with the recognition of the group by D Lo et al; who showed for the first time that cell-free fetal DNA in maternal plasma and serum can be used reliably for prenatal diagnosis. One of the first successful applications was the detection of the fetal Rhesus factor around 11 weeks of gestation in pregnancies of Rhesus-negative mothers. The Sequenom Company in San Diego, USA, which acquired the patent of D Lo et al on the use of cell free DNA and ours on size separation of fetal vs maternal DNA subsequently showed in large series that the noninvasive prenatal diagnosis of fetal trisomy 21 from maternal blood by massive parallel sequencing has an accuracy around 99%, and currently up to 100,000 cases have been investigated already in different laboratories. Also the noninvasive prenatal diagnosis of trisomies 18 and 13 is possible, and an increasing amount of single gene anomalies will be diagnosable in the future noninvasively. The whole development of noninvasive prenatal diagnosis is appositive example that long-term research pays-off to bring a concept from the first steps finally into clinical use.
How to cite this article
Holzgreve W. Noninvasive Prenatal Diagnosis from Maternal Blood: Finally Available after 20 Years of Research. Donald School J Ultrasound Obstet Gynecol 2013;7(4):440-442.
Noninvasive Prenatal Detection of Trisomy 21 by an Epigenetic–Genetic Chromosome-Dosage Approach