Implementation of maternal blood cell-free DNA testing in early screening for aneuploidies

Abstract

Several externally blinded validation and implementation studies in the last 9 years have shown that it is now possible, through analysis of cell-free (cf) DNA in maternal blood, to effectively detect a high proportion of fetuses affected by trisomies 21, 18, and 13 at a much lower false-positive rate (FPR) than all other existing screening methods. This article is aimed at reviewing technical and clinical considerations for implementing cfDNA testing in routine practice, including methods of analysis, performance of the test, models for clinical implementation, and interpretation of results.

Comparison of first‐tier cell‐free DNA screening for common aneuploidies with conventional publically funded screening

“…Pregnancy outcomes were not available but FPR and impact on diagnostic testing were reported. 17 Although the implementation of NIPS as a first-tier test would have the benefit of reducing the number of invasive diagnostic procedures, some argue that it would also decrease the number of chromosomal abnormalities other than the common aneuploidies that are currently detected by traditional screening approaches. 12,13 Karyotype analysis of invasive prenatal testing in singleton pregnancies performed for a positive prenatal traditional screen in a cohort of 1 324 607 women identified an atypical chromosomal abnormality likely to result in an abnormal phenotype and not likely detectable by NIPS in 1.4% of the 68 990 pregnancies with a positive screen, suggesting that these abnormal pregnancies would not be detected were cfDNA analysis to replace standard screening.…”

A prospective clinical trial to compare the performance of dried blood spots prenatal screening for Down’s syndrome with conventional non-invasive testing technology

“…Since Lo et al 26 first described the presence of circulating fetal cfDNA in maternal plasma in 1997, its diagnostic value has come into clinic with amber applications including prenatal chromosomal aneuploidy detection. 14,[27][28][29] Gradually, maternal plasma cfDNA scrutiny has integrated into routine prenatal care mostly in detecting chromosomal aneuploidy, after a transition of experimental and clinical validation of the methodology. 27 From the year of 2011, fetal cfDNA analysis has been approved to be incorporated into prenatal care clinic as an alternative to fetal screening technology in the United States 14 and elsewhere across the world.…”

Preimplantation genetic screening: Changes in technology and methodology, ethical implications, and areas of future research

“…One example of further testing is maternal blood cell testing for alpha-fetoprotein, which can indicate a risk for neural tube defects (Burke et al, 2011). Maternal blood can also be used for DNA testing, to detect aneuploidies in the developing fetus (Gil et al, 2013). Maternal blood testing has a high success rate of determining trisomies 21, 18, and 13, and when implemented in the first trimester of pregnancy, can either reassure parents early on that their child is unlikely to possess a trisomy mutation or provide parents of an affected fetus early counselling or access to earlier and safer pregnancy termination options (Gil et al, 2013).…”