A reanalysis of previously generated sequencing data from the general-risk Comparison of Aneuploidy Risk Evaluations (CARE) study was published in the New England Journal of Medicine, and offers new insight into false-positive results generated by non-invasive prenatal testing (NIPT). The letter, entitled “Copy-Number Variation and False Positive Prenatal Screening Results,” features new data after informatics updates were made to Illumina’s verifi® Prenatal Test. The modifications were made to reduce technical and biological variances and resulted in six fewer false positive cases than the 11 originally reported in the study cohort.
The 2014 study demonstrated that Illumina’s verifi® Prenatal Test could significantly improve clinical practice by reducing the number of invasive procedures needed to clarify false-positive results obtained with standard screening. In the CARE study cohort, 1,914 samples were analyzed and 11 false positives were originally recorded. The reanalysis resulted in six fewer false-positive cases, with the NIPT classification changing from “aneuploidy detected” to “no aneuploidy detected.” Three cases were attributed to the presence of maternal copy-number variants, which the algorithm now corrects for, and three were attributed to improved normalization steps.
“The current standard of care using serum screening has only a 5 percent positive predictive value, meaning a positive screen result is only associated with a fetal chromosomal abnormality in 1 of 20 cases,” said Diana W. Bianchi, M.D., Executive Director of the Mother Infant Research Institute at Tufts Medical Center, and senior author of the letter and lead author of the original study. “The reanalyzed CARE data using verifi® shows that maternal plasma DNA testing is a much more accurate screen.”
Illumina’s Reproductive and Genetic Health solutions use next-generation sequencing (NGS) technology and advanced microarrays to generate comprehensive, accurate genomic information to assist healthcare providers and patients in making informed decisions for their reproductive health and well-being. Illumina offers the non-invasive verifi® prenatal test (formerly offered by Verinata Health, Inc.) in its CLIA-certified, CAP-accredited clinical services laboratory, to detect certain chromosome abnormalities and aberrations with improved resolution for consistent and dependable results. The verifi® Prenatal Test screens for multiple fetal chromosomal aneuploidies using a single maternal blood draw and can be done as early as 10 weeks gestational age.
“This reanalysis of the CARE data shows that there are both technical and biologic reasons for the original false-positive results. Biological reasons include maternal copy number variations and fetoplacental mosaicism,” said Jeff Hawkins, Vice President and General Manager of Illumina’s Reproductive Genetic Health business. “As we continue to make improvements in our informatics algorithms, this will lead to improved verifi® test performance.”