Cell-Free DNA Test Highly Accurate as Prenatal Screen

October 03, 2012

NEW YORK (Reuters Health) Oct 01 - A test that analyzes cell-free DNA in maternal blood is a "highly accurate" way to detect fetal aneuploidy, researchers say.

The Harmony Prenatal Test (Ariosa Diagnostics Inc), done in 2,049 women undergoing routine prenatal screening, had a 99% detection rate and a false positive rate below 1%.

"On the basis of existing data, non-invasive prenatal testing (NIPT) can potentially be used in universal screening for trisomies 21 and 18 in all singleton pregnancies and the main limiting factor for such widespread application of the test at present is cost," Dr. Kypros H. Nicolaides and colleagues from King's College Hospital in London conclude.

Previous studies have tested cell-free DNA (cfDNA) techniques in high risk women, Dr. Nicolaides and his colleagues note in the American Journal of Obstetrics and Gynecology.

To determine if NIPT would be effective in a population with a lower prevalence of aneuploidy, the researchers tested stored plasma samples from 2,049 pregnant women who underwent routine screening at 11 to 13 weeks' gestation.

Results from chromosome-selective sequencing were available for 1,949 cases; in 46, the fetal fraction was below the minimum requirement of 4%, and in 54 cases there was assay failure. There were eight cases of trisomy 21 and two trisomy 18 cases.

Risk scores based on chromosome-selective sequencing for trisomy 21 were >99% for all cases of trisomy 21 and <0.01% for the trisomy 18 cases. Testing for trisomy 18 yielded a >99% risk score for the two cases of trisomy 18, and <0.01% for the cases of trisomy 21.

Among the 1,939 proven or assumed euploid pregnancies, 1,936 had risk scores of <0.01%, and risk scores were below 1% in 1,937. Two of the euploid pregnancies had trisomy 18 risk scores of 9.8% and 11.7%, respectively. The authors suggest that the two false-positive cases could have been due to placenta-confined mosaicism.

"The sensitivity and specificity of NIPT is not 100% and therefore it should not be considered a diagnostic test to replace invasive testing in high-risk pregnancies," Dr. Nicolaides and colleagues write. "It is a new screening test that identifies a high-risk group requiring further investigation by invasive testing."

Nor should the test replace the 11- to 13-week scan, the researchers add.

"The latter is not only useful in screening for aneuploidies but it is a diagnostic test for many major fetal defects and in combination with biochemical and other biophysical markers can provide effective early screening for pregnancy complications, including pre-eclampsia and preterm birth," they conclude.

Dr. Nicolaides did not respond to a request for an interview by press time.

The study was supported by a grant from the UK's Fetal Medicine Foundation and by Ariosa Diagnostics Inc, San Jose, California.

SOURCE: http://bit.ly/SYFSr2

Am J Obstet Gynecol 2012.