Clinical experience of laboratory follow‐up with noninvasive prenatal testing using cell‐free DNA and positive microdeletion results in 349 cases. (26th February 2018)

• Record Type: Journal Article
• Authors: Schwartz, S.; Kohan, M.; Pasion, R.; Papenhausen, P. R.; Platt, L. D.
• Is Part Of: Prenatal diagnosis. Volume 38:Number 3(2018)
• Page Start: 210
• Page End: 218
• Publication Date: 2018-02-26
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.5217
• Languages: English
• ISSNs: 0197-3851

Abstract

Abstract: Objective: Screening via noninvasive prenatal testing (NIPT) involving the analysis of cell‐free DNA (cfDNA) from plasma has become readily available to screen for chromosomal and DNA aberrations through maternal blood. This report reviews a laboratory's experience with follow‐up of positive NIPT screens for microdeletions. Methods: Patients that were screened positive by NIPT for a microdeletion involving 1p, 4p, 5p, 15q, or 22q who underwent diagnostic studies by either chorionic villus sampling or amniocentesis were evaluated. Results: The overall positive predictive value for 349 patients was 9.2%. When a microdeletion was confirmed, 39.3% of the cases had additional abnormal microarray findings. Unrelated abnormal microarray findings were detected in 11.8% of the patients in whom the screen positive microdeletion was not confirmed. Stretches of homozygosity in the microdeletion were frequently associated with a false positive cfDNA microdeletion result. Conclusions: Overall, this report reveals that while cfDNA analysis will screen for microdeletions, the positive predictive value is low; in our series it is 9.2%. Therefore, the patient should be counseled accordingly. Confirmatory diagnostic microarray studies are imperative because of the high percentage of false positives and the frequent additional abnormalities not delineated by cfDNA analysis. Abstract : What's already known about this topic? cfDNA is shown to be effective for prenatal detection of aneuploides. cfDNA has been used to detect microdeletions prenatally, but studies are limited. What does this study add? This is one of the largest follow‐up diagnostic studies to cfDNA detection of microdeletions. This manuscript provides clear evidence of the importance of follow‐up of cfDNA testing with diagnostic microarray analysis.