Trisomy and Circulating DNA

Pregnant women have a lot on their minds, I'm sure we'd all agree.  What with environmental exposures, mortality related to flu strains, psychoactive medications and even OTC meds, it's a wonder the process can be undertaken with any degree of composure.  Enter now, as Rick and I discuss on PodMed, a new type of test that is quick, noninvasive, and very reliable for indicating risk that a fetus might have a genetic abnormality known as aneuploidy, or too many copies of specific chromosomes, as published in this week's NEJM.  The test has the potential to reduce anxiety for pregnant women who undergo routine screening that more often than would be desirable indicates a potential problem.  Not only that, but for the nerds among us the technology is way cool and is rapidly making its way through many other areas of clinical medicine.  What's it about?

Turns out that a bit of fetal DNA is shed from the fetal contribution to the placenta into the maternal circulation.  In the common vernacular that's some of the baby's DNA makes it into mom's bloodstream. This is known in the parlance as cell-free DNA or cfDNA.  There it can be detected when blood is withdrawn by a technique known as 'massively parallel sequencing.'  Yikes.  That means the baby's DNA fragments are detected and copied and analyzed to determine if too many copies of chromosomes 18 or 21 are present. These conditions are known as 'Edwards syndrome' and 'Downs syndrome.'  This last is the most common aneuploidy compatible with life, affecting some 1 in 800 live births and becoming increasingly common with increased maternal age.  Edwards syndrome affects 1 in 6000 live births.

This study is an extension of previous work demonstrating that this technique could be used with great sensitivity and specificity in women at high risk for having a fetus with an aneuploidy, such as older age or a previous pregnancy where aneuploidy was detected. In this case a multitude of low risk women were enrolled, and here's what the results report:

The primary series included 1914 women (mean age, 29.6 years) with an eligible sample, a singleton fetus without aneuploidy, results from cfDNA testing, and a risk classification based on standard screening. For trisomies 21 and 18, the false positive rates with cfDNA testing were significantly lower than those with standard screening (0.3% vs. 3.6% for trisomy 21, P<0.001; and 0.2% vs. 0.6% for trisomy 18, P=0.03). The use of cfDNA testing detected all cases of aneuploidy (5 for trisomy 21, 2 for trisomy 18, and 1 for trisomy 13; negative predictive value, 100% [95% confidence interval, 99.8 to 100]). The positive predictive values for cfDNA testing versus standard screening were 45.5% versus 4.2% for trisomy 21 and 40.0% versus 8.3% for trisomy 18.  This is impressive, we must admit, and calls for adoption of this screening for all pregnant women who choose to be screened.

Other topics this week include an enterovirus vaccine developed in China and causes of fever in African children in NEJM, and another analysis of vitamin E and selenium supplements and prostate cancer in the Journal of the National Cancer Institute.  Until next week, y'all live well.

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