Improvement of algorithm based on free DNA fragment size for non-invasive prenatal test

Abstract

To derive more sensitive and accurate Z-scores for noninvasive prenatal testing of fetal trisomies based on a combined DNA count- and size- algorithm. One hundred eighty women at a high risk for fetal aneuploidies underwent amniocentesis. An effective cut-off value for DNA size ratio was explored. Conventional count-based Z-scores and size ratio-corrected Z scores were calculated. The reliability of each Z-score was assessed through comparison with the results of cytogenetic analysis. With the cut-off value set as 150 bp, the ratio of small DNA is positively correlated with the proportion of fetal DNA. The sensitivity and specificity of conventional count-based Z-scores were 75.00%, and 98.86%, respectively. This rate has increased to nearly 100% with a count-based 150 bp size correction. Compared with count-based methods alone, count-based Z-scores with 150 bp size correction may better predict fetal trisomies.