Top developments in Down syndrome prenatal testing for 2013

Finishing the year-in-review posts, here are what I believe are the developments in Down syndrome prenatal testing that had and will have the greatest impact from 2013:

1. Non-invasive prenatal screening goes mainstream: introduced on October 17, 2011 in 20 select cities by Sequenom, the newest form of Down syndrome prenatal testing went mainstream in 2013. In 2012, other labs joined the marketplace with their tests–Verinata’s verifi and Ariosa’s Harmony. Natera joined with its Panorama test in 2013. Each lab issued press release after press release of the tens of thousands of tests performed, with labs also going international, adding tens of countries that are now offering NIPS. Last year ended with ACOG issuing a statement recognizing NIPS for mothers considered “high-risk.” In 2013, ACMG, ISPD, and NSGC all joined suit, issuing their own statements. With this professional acknowledgement, insurers soon followed, covering the cost of NIPS in many instances. 2013 was the year when Down syndrome testing was forever changed, with NIPS being accepted as part of the testing protocol for expectant mothers.
2. The rest of the genetic iceberg to be revealed: a common metaphor I (and many others) have used for Down syndrome prenatal testing is that Down syndrome is just the tip of the genetic iceberg. Down syndrome is at the forefront of genetic testing mainly because it’s easy: all a lab tech has to do is count past 46 and they have found a trisomy, with Down syndrome being the most common. But, there are thousands upon thousands of genetic variations. This month, ACOG and the Society for Maternal-Fetal Medicine closes out 2013 by recommending that the rest of the genetic iceberg be tested for when a woman undergoes invasive testing. The ACOG/SMFM joint committee opinion recommends microarray testing as a first-tier invasive test. The opinion does so even while relying on a study of mothers who described microarray test results as “toxic knowledge,” for their uncertainty about what the genetic variation diagnosed could even mean, if anything, for their developing child. This new era of ever more genetic knowledge led to the third significant development:
3. Pre- and post-test genetic counseling now recommended by professional guidelines: In the professional statements on NIPS and microarray testing, for the first time, the professional organizations recognize that the state of prenatal testing has outpaced both professional and patient understanding. While NIPS can be a more accurate screening test of certain populations, it remains a screening test, but this can be lost on patients (and practitioners) when it is described as the “Holy Grail” and test results are returned as “consistent with Trisomy 21.” With microarray testing, it can return so much information, including consanguinity, paternity, and conditions that could affect the parents. Therefore, the professional organizations emphasized the need for both pre-test counseling and post-test counseling for NIPS and microarray testing in an effort to respect patient autonomy and increase the chance that informed decisions are made.
4. Down syndrome “reversed,” “turned off,” “cured”: In July, it was announced that researchers had “turned off” the extra 21st Chromosome that is the genetic cause of Down syndrome. They did so by inserting a gene (ironically called XIST) from the X chromosome, which turns off the other X chromosomes in females, onto the 21st Chromosome to turn off the third copy. While the lead researcher cautioned that their research did not promise a “cure,” to the extent it could be applied, it would be at the embryonic stage. Soon thereafter, a different team of researchers “reversed” the cognitive delay effects associated with Down syndrome in mouse models by injecting a compound into the mice’s brains called “sonic hedgehog.” These developments stirred a reflection on what Down syndrome is: a disease to be cured or a part of the genetic diversity that makes up the human family? Further, one of the lead NIPS developers wrote that this promise of potential treatments casts prenatal testing in a different light: rather than allowing for the termination of the pregnancy, with possible prenatal treatments, prenatal testing could be seen as therapeutic. But, given the 5th development, will these treatments arrive too late before the first option becomes seen as the norm?
5. The elimination of Down syndrome: Studies from other countries suggest a one-way bent in the trends following the roll-out of prenatal testing: more selective abortions of pregnancies following a prenatal result for Down syndrome. Taiwan reported that it was experiencing a 94% termination rate of all Down syndrome pregnancies, attributing the dramatic decrease in live births to increasing uptake of prenatal testing. Similarly, Sweden announced that after just a few years of instituting a prenatal testing program, there had been an increase in selective terminations following a positive prenatal result. The trend towards elimination was so much in Denmark–where prenatal testing had reduced the number of live births by two-thirds–that a photographer decided he needed to document a life of a  family with a child with Down syndrome because such a life was becoming so exceedingly rare. In February, the Atlantic ran a headline, “Better prenatal testing does not mean more abortions,” but the headlines this year suggest the contrary is true.

Newer prenatal testing is becoming part of standard prenatal care, with more genetic information than ever to be returned, justifying pre- and post-test counseling. That counseling may ultimately include information on possible prenatal treatments, but the current trend is towards selective termination following a prenatal test result. These developments will shape the administration of prenatal testing and lives with Down syndrome in the coming years.

If I missed a news item bearing on Down syndrome and prenatal testing from 2013 that you think should be on this list, I invite you to leave a comment below.