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?
Prenatal cfDNA screening, often called NIPT, has given rise to many differences of opinion among professional societies. Recommendations about using cfDNA for prenatal screening have evolved slowly as studies have validated these tests – and, of course, as the tests themselves have changed and expanded over time. ACMG, representing medical genetics and laboratories, has tended to make the most expansive recommendations in favor of cfDNA screening, while ACOG, representing the bulk of obstetricians, has tended to be the most conservative group. Others, like ISPD, have usually fallen between the two extremes.
Commercial cfDNA labs, for their part, have grumbled about what they see as an overly slow pace of accepting this new technology (although, by historical medical standards, it’s actually been quite fast). One of their long-standing complaints has been revived in a just-published commentary in Prenatal Diagnosis. Adam Wolfberg, formerly employed by Ariosa (the makers of the Harmony™ cfDNA screen), argues in this new commentary that professional bodies have an inherent conflict of interest that has led them to resist more enthusiastic recommendation for prenatal cfDNA screening. Maternal-fetal medicine (MFM) specialists, he argues, see their livelihood endangered by this new technology, which threatens to undermine the fetal ultrasounds that are their bread and butter. Continue reading Are professional societies conflicted about cfDNA?
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.
As part of their series of studies reviewing demographic statistics to estimate prevalence and total population of individuals with Down syndrome, Dr. Brian Skotko and his team of researchers have now delved into the numbers for nine specific states. Based on their analysis, while pregnancies positive for Down syndrome are at an all-time high, the number of babies born has plateaued with the introduction of prenatal testing. Continue reading Study estimates population & prevalence of Down syndrome in nine U.S. states
Hello from Kansas City, the geographical center of the US, where the American Society for Bioethics and Humanities is holding its annual meeting! Several PIRCers are here presenting research and learning from colleagues in bioethics.
Michelle McGowan is speaking on reproductive ethics to the Reproduction Affinity Group of ASBH, Saturday October 21st at 6pm. Marsha Michie is delivering a paper, “Scaffolding Translation: A Model for Ethical and Social Guidance of Translational Genomic Medicine,” Saturday at 2pm, based on her research on prenatal cell-free DNA screening. Jessica Mozersky and Stephanie Kraft are speaking on other topics: Jessica on “How Do Clinical Research Coordinators Actually Gain Knowledge of Good Clinical Practice?” Sunday at 11am, and Stephanie as part of a panel on “Beyond the Therapeutic Misconception: The Challenges of New Misconceptions About Research,” Thursday at 4pm.
You can peruse the whole program for the 2017 ASBH meetings at asbh.org.