Another roundup of research presented at this year’s ACMG conference on prenatal testing for Down syndrome and other genetic conditions.
Poster 593: Double trisomy detected through integrated screening: Down syndrome and trisomy 18.
Out of 88,000+ pregnancies, 35 received screen results indicating both Trisomy 21 and 18. The take away:
Our data confirm that there is a high likelihood of a poor pregnancy outcome when the IPS is positive for both Down syndrome and trisomy 18, with only 17.1% of pregnancies culminating in the live birth of a healthy, chromosomally normal infant. This information may help health care providers to convey realistic expectations to women they are counseling with double positive IPS results.
Or, it may help convey that screening tests are just that, and while Double Trisomy is more likely than not based on a screen result, there still remains a 17% chance of it being a false positive.
Poster 601: what does a “positive” NIPS result mean for Trisomy 18 or 13? At this clinic, it means more than likely, you are NOT carrying a child with Trisomy 18 or 13:
Conclusion: Because of the low prevalence of trisomies 13 and 18, the majority of women with positive test results for trisomies 13 and 18 have actually normal fetuses. Accurate counseling of such cases is essential because the high accuracy of the test in terms of detection rate and specificity may be misunderstood as implying a high positive predictive value
Poster 603: Adam Wolfberg last year disagreed with the recommendations to only offer NIPS to women who were considered “high-risk,” making NIPS a second-tier test. This despite research he participated in showing NIPS was more accurate in the high risk population and not in the low risk population. Undaunted, Wolfberg admitted to offering NIPS to all women, not just those with a traditional screen result, or another risk indicator. In 2014, as lead author this time, he presented research that concluded:
The use of first-trimester ultrasound prior to non-invasive screening led to early diagnosis of aneuploidy in a general-screening population. NIPT test performance in this population demonstrated a high degree of accuracy.
Soon after calling for NIPS as a first-tier test, Wolfberg joined the NIPS lab Ariosa. His own research, though, supports NIPS being offered to the high risk population, but not the low risk population.
Poster 607: NIPS rules out aneuploidy in sample of patients with isolated echogenic intracardiac focus (EIF). All EIF indicated pregnancies that returned results were screened negative by NIPS, avoiding the risk of miscarriage from follow-up invasive testing. The study concludes:
This cohort provides clinical evidence to support the role of a NIPT as an option for aneuploidy screening in the context of isolated EIF, minimizing the need for invasive procedures in this setting.
Poster 609: those affiliated with Ariosa conducted a study to compare NIPS with first trimester nuchal translucency combined testing (NT) to see which was more effective in the general population, e.g. regardless of risk assessment, patients were offered both tests. Results:
1116 women were offered prenatal testing for aneuploidy. The mean maternal age was 32.25 years (range: 18-49). … 134 (17.5%) women declined all testing[;] 412 women (37%) chose NIPT either as first-line testing option or following FTS. …
There were 4 total high risk results (0.98% test positive rate). In 2 cases there was > 99% probability for Trisomy 21 both of which were confirmed by CVS. The other 2 cases had a >99% probability for Trisomy 13. One case spontaneously miscarried and the other was confirmed trisomy 13 by amniocentesis. Interestingly, this case had a negative FTS but patient elected to also have NIPT (1.6 mm NT, FTS: 1/2,465 risk for Trisomy 21, 1/4721 risk for Trisomy 18/13). Of those choosing FTS (n= 688), there was a 4% (n=26) screen positive rate (lab cut off = 1/311). 24 out of 26(92%) declined invasive testing, but 17 of FTS screen positive patients had follow-up NIPT which reported a low risk result.
NIPT leads to a lower test positive rate in this general population compared to FTS when used as a first-line test. The average age of patients choosing NIPT is <35 years of age. While payer reimbursement policies have evolved since NIPT was first introduced in 2012 not all patients interested in having NIPT can obtain coverage for this test.
But see Poster 603 above regarding NIPS still more accurate as a second-tier screen, and Poster 601 regarding most “positive” NIPS for Trisomy 18 or 13 turning out to be false.