The American College of Medical Genetics and Genomics (ACMG) believes that the application of genetic technology, particularly when used in the prenatal setting, needs to be supported by prospective clinical trials and considered carefully before its incorporation into routine clinical care. The ACMG has previously published guidelines on prenatal screening for Down syndrome, which have successfully assisted health-care providers and their patients during pregnancy.
1One of the major breakthroughs in obstetrical care was the advent of prenatal genetic diagnosis, initially by amniocentesis in the second trimester of pregnancy. Subsequently, chorionic villus sampling during the first trimester allowed for earlier diagnosis and management. However, the potential risk of fetal loss secondary to an invasive procedure has driven the search for noninvasive approaches for genetic screening and diagnosis. Until recently, noninvasive screening for aneuploidy relied on either the measurement of maternal serum analytes and/or ultrasonography with positive screen rates of ~5% and detection rates of 50-95%, depending on the screening strategy utilized. More recent advances in genomics and genomic technologies have resulted in the development of a noninvasive prenatal screening (NIPS) test using cell-free fetal DNA sequences isolated from a maternal blood sample.2-6 About 10% of DNA in maternal serum is of fetal origin; 4,7,8 this has been used for prenatal Rh determination and gender identification. Using nextgeneration sequencing platforms, millions of amplified genetic fragments can be sequenced in parallel (massively parallel sequencing). Platforms differ according to whether amplified regions throughout the genome, chromosome-specific regions, or single-nucleotide polymorphisms are the targets for sequencing. Furthermore, by using powerful bioinformatics tools, differences between maternal and fetal sequences and dosage differences in identical sequences or a reference chromosome can be determined and used for noninvasive screening for fetal aneuploidy. 9,10 Although studies are promising and demonstrate high sensitivity and specificity with low false-positive rates, there are limitations to NIPS. Specificity and sensitivity are not uniform for Noninvasive assessment of the fetal genome is now possible using next-generation sequencing technologies. The isolation of fetal DNA fragments from maternal circulation in sufficient quantity and sizes, together with proprietary bioinformatics tools, now allows patients the option of noninvasive fetal aneuploidy screening. However, obstetric care providers must become familiar with the advantages and disadvantages of the utilization of this approach as analysis of cell-free fetal DNA moves into clinical practice. Once informed, clinicians can provide efficient pretest and posttest counseling with the goal of avoiding patient harm. It is in the public's best interest that test results contain key elements and that laboratories adhere to established quality control and proficiency te...