Cell-Free DNA Test Most Accurate for Trisomy 21 Screening

By Reuters Staff

February 12, 2015

NEW YORK (Reuters Health) - Screening for Down syndrome by analyzing cell-free DNA (cfDNA) in maternal blood has a higher detection rate and lower false-positive rate than other screening approaches, the authors of a new meta-analysis conclude.

However, the cost of the test and its relatively high failure rate mean it would be inappropriate for use as first-line trisomy 21 screening, Dr. K. H. Nicolaides, of King's College Hospital in London, and colleagues state. Instead, they argue, the test-which can be done at 10-11 weeks' gestation--should be used for contingent screening based on the results of another noninvasive screening method, ideally the first-trimester combined test.

The researchers had previously completed a review of screening for fetal aneuploidy with cfDNA that included studies published from 2011 to 2013. In the new meta-analysis, Dr. Nicolaides and colleagues looked at a total of 37 studies published up to January 4, 2015.

Twenty-four of the studies, including 1,051 affected pregnancies and 21,608 unaffected pregnancies, examined cfDNA screening of singleton pregnancies for trisomy 21. The detection rate was over 99%, with a false-positive rate below 0.1%.

Twenty-one studies investigated cfDNA screening for trisomy 18, and included 389 affected cases and 21,306 unaffected cases. The pooled, weighted detection rate was about 96%, while the false-positive rate was 0.13%.

Eighteen studies looked at cfDNA analysis for trisomy 13 screening, and included 139 affected pregnancies and 18,059 unaffected pregnancies. Detection rate was 91%, and false-positive rate was 0.13%.

Sixteen studies looked at detection of monosomy X, and included 177 affected singleton pregnancies and 9,079 unaffected pregnancies. Pooled detection rate was 90.3%, while the false positive rate was 0.23%.

There were a dozen studies reporting performance of cfDNA for other sex chromosome aneuploidies, with 56 affected pregnancies and 6,699 unaffected pregnancies, for a pooled detection rate of 93% and a false positive rate of 0.14%.

"There are essentially two options in the clinical implementation of cfDNA analysis of maternal blood in screening for trisomy 21: first, routine screening of the whole population, and second, contingent screening based on the results of first-line screening by another method, preferably the first-trimester combined test," the researchers write.

The most important issues with using the cfDNA test for universal screening, they add, are the cost of the test and the rate of failure to provide a result, but these issues could be resolved by using cfDNA testing for contingent screening.

"This strategy would also retain the advantages of first-trimester testing by ultrasound and biochemistry, including accurate pregnancy dating, early detection of many major fetal defects and prediction, with the potential of prevention, of a wide range of pregnancy complications, including pre-eclampsia and preterm birth," the researchers add.

Expanding indications of cfDNA screening to include trisomy 18, trisomy 13, and sex chromosome aneuploidies would increase the false positive rate to 0.72%, the authors note. And the performance of the test in screening twin pregnancies for trisomy 21 "requires further evaluation."

The authors report no external funding or disclosures.

SOURCE: http://bit.ly/1AZfCbK

Ultrasound Obstet Gynecol 2015.

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