By Linda Carroll

Not even one of the commercial labs offering “cell-free” noninvasive prenatal screening for chromosomal disorders is fully following the recommendations published by the American College of Medical Genetics, according to a new report.

The report was put together by a team of specialists in medical genetics and published in Genetics in Medicine.

The ACMG made it clear in 2016 that labs should not offer this screening if they could not follow the suggested guidelines, said the new report’s lead author, Dr. Brian Skotko, the Emma Campbell Endowed Chair on Down Syndrome at Massachusetts General Hospital and an associate professor at Harvard Medical School in Boston.

The tests, known as noninvasive prenatal screening, or NIPS, are meant to be used as a sort of pre-screening so that women whose fetus has a low risk of having a chromosomal abnormality won’t need to get more invasive tests, like amniocentesis.

The NIPS tests look at bits of DNA in the prospective mother’s blood that broke off from the placenta. The labs count up “free floating fragments of chromosomes,” Skotko explained. The theory is that if a fetus has Down syndrome, for example, which is marked by three rather than two copies of chromosome 21, many more copies of this chromosome will be found in the mother’s blood sample, as compared to other chromosomes.

“When you find an overabundance of 21 then you’re able to predict whether or not it’s because the fetus has Down syndrome,” Skotko said. But it’s not an exact science and that’s why “ACMG was clear from the beginning that this was a screening test, not a diagnostic one,” he added.

Using the numbers from the blood sample, along with other factors like the mother’s age, the labs can calculate what percentage of fetuses with similar results had Down syndrome.

The problem is that some labs are simply reporting results as positive or negative. But there is a wide range of positive percentages, and without knowing how high the number is, parents can’t make an informed choice, Skotko said. If for example, there’s a 95 percent chance that the baby has Down syndrome, then the parents can either go on to have a diagnostic amniocentesis, which carries a small, but real, risk of miscarriage, or they can decide to educate themselves about the condition so they’ll be ready when the baby comes, Skotko said. “Expecting couples want to know the percentage,” he added.

Another recommendation, seemingly ignored by some labs, was to provide education to the prospective parents. This could include links to websites that would provide information on the tests and on the conditions the fetus might have.

“We want to shine a flashlight on their adherence or lack of adherence so there will be a transparent way physicians and couples can make the most accurate decisions,” Skotko said.

The new report includes a table listing companies offering NIPS plotted against the list of recommendations. Where a company has followed a recommendation, the table shows a green dot, where they haven’t, a red dot.

“We want this big table to be replaced by one with all green dots,” Skotko said.

The new report is “really interesting,” said Dr. Leena Nathan, an obstetrician-gynecologist and an assistant clinical professor at the University of California, Los Angeles. “It was surprising to see there was no standardization.”

And that’s very important, Nathan said, adding that the ob-gyns at her hospital were about to have a meeting to discuss which lab would be best to use. “This is a very helpful table,” she said. “And we will look closely at it and discuss it as a group as we decide which company to go with.”

SOURCE: https://go.nature.com/2I0yoJp Genetics in Medicine, online April 3, 2019.