One of the major selling points for prenatal cell-free DNA (cfDNA) screening has been that it will reduce the number of miscarriages resulting from invasive diagnostic tests–amniocentesis and CVS. However, a randomized controlled trial in France, just published (paywall) in the Journal of the American Medical Association, has found no evidence of this promised benefit.
The SAFE21 Study Group randomized “high risk” pregnant women in 57 French clinics to either go straight to invasive diagnosis or, alternately, to have cfDNA screening first. Those in the cfDNA arm of the trial received invasive testing only if the cfDNA screen returned positive results. There were just over 1000 women assigned to each arm of the trial. In the cfDNA arm, nearly all the women had cfDNA screening, and 84 women (8.3%) had follow-up invasive diagnosis. Yet the miscarriage rate for the cfDNA arm was identical to that for the invasive testing arm, in which 751 women (76.5%) had invasive diagnosis. In each arm 8 women (0.8%) experienced miscarriage. Furthermore, in the invasive testing arm, researchers discovered 11 chromosomal anomalies (1.5%) that would not have been found using cfDNA screening. Continue reading No safety differences between cfDNA screening and diagnostic testing?
Genome-wide sequencing is increasingly being conducted on fetal tissues, either as whole exome sequencing (WES), whole genome sequencing (WGS), or targeted analysis that uses clinical panels. These kinds of prenatal sequencing are sometimes done when more standard genetic tests have not yielded helpful results to explain structural anomalies, or if a specific genetic condition is suspected that would not be detected through other prenatal tests. While such sequencing is more likely to yield a positive result, it comes with its own set of risks and challenges – for instance, it is more likely to detect variants of unknown significance and other results that lead to excessive testing and stress on parents without significant benefit.
The International Society of Prenatal Diagnosis (ISPD), in conjunction with the Society of Maternal Fetal Medicine (SMFM) and the Perinatal Quality Foundation (PQF), just issued a joint position statement on the use of genome-wide sequencing for fetal diagnosis. While they recognize that sequencing can be useful in some instances, they generally take a cautionary approach. Based on “lessons learned from existing prenatal testing,” along with currently available literature and a panel discussion at the most recent annual ISPD meetings, their consensus opinion includes the following points. Continue reading ISPD issues new guidelines for prenatal genome-wide sequencing
A new study reports on the impact of noninvasive prenatal genetic screening (“NIPGS”) on referrals for diagnostic testing. It finds plummeting diagnostic testing and more. Continue reading More NIPGS = More Misdiagnoses and Risk