ABSTRACT
OBJECTIVE: To evaluate clinical performance of a new automated cell-free (cf)DNA assay in maternal plasma screening for trisomies 21, 18, and 13, and to determine fetal sex. METHOD: Maternal plasma samples from 1200 singleton pregnancies were analyzed with a new non-sequencing cfDNA method, which is based on imaging and counting specific chromosome targets. Reference outcomes were determined by either cytogenetic testing, of amniotic fluid or chorionic villi, or clinical examination of neonates. RESULTS: The samples examined included 158 fetal aneuploidies. Sensitivity was 100% (112/112) for trisomy 21, 89% (32/36) for trisomy 18, and 100% (10/10) for trisomy 13. The respective specificities were 100%, 99.5%, and 99.9%. There were five first pass failures (0.4%), all in unaffected pregnancies. Sex classification was performed on 979 of the samples and 99.6% (975/979) provided a concordant result. CONCLUSION: The new automated cfDNA assay has high sensitivity and specificity for trisomies 21, 18, and 13 and accurate classification of fetal sex, while maintaining a low failure rate. The study demonstrated that cfDNA testing can be simplified and automated to reduce cost and thereby enabling wider population-based screening.
Subject(s)
Noninvasive Prenatal Testing/methods , Trisomy/diagnosis , Chromosomes, Human, Pair 13 , Chromosomes, Human, Pair 18 , Chromosomes, Human, Pair 21 , Female , Humans , PregnancyABSTRACT
Cell-free DNA analysis is becoming adopted for first line aneuploidy screening, however for most healthcare programs, cost and workflow complexity is limiting adoption of the test. We report a novel cost effective method, the Vanadis NIPT assay, designed for high precision digitally-enabled measurement of chromosomal aneuploidies in maternal plasma. Reducing NIPT assay complexity is achieved by using novel molecular probe technology that specifically label target chromosomes combined with a new readout format using a nanofilter to enrich single molecules for imaging and counting without DNA amplification, microarrays or sequencing. The primary objective of this study was to assess the Vanadis NIPT assay with respect to analytical precision and clinical feasibility. Analysis of reference DNA samples indicate that samples which are challenging to analyze with low fetal-fraction can be readily detected with a limit of detection determined at <2% fetal-fraction. In total of 286 clinical samples were analysed and 30 out of 30 pregnancies affected by trisomy 21 were classified correctly. This method has the potential to make cost effective NIPT more widely available with more women benefiting from superior detection and false positive rates.
Subject(s)
Cell-Free Nucleic Acids/blood , Down Syndrome/diagnosis , Prenatal Diagnosis/methods , Single Molecule Imaging/methods , Aneuploidy , Case-Control Studies , Cost-Benefit Analysis , Female , Humans , Pregnancy , Prenatal Diagnosis/economics , Prospective Studies , Single Molecule Imaging/economicsABSTRACT
UNLABELLED: The Inman Aligner is a highly effective and unique evolution of the traditional spring retainer that uses super-elastic Nickel-Titanium open coil springs to move upper and lower anterior teeth with light but consistent forces, enabling correction of anterior crowding, rotations and some types of spacing. CLINICAL RELEVANCE: This article describes the appliance, its uses and limitations.
Subject(s)
Orthodontic Appliance Design , Orthodontic Wires , Tooth Movement Techniques/instrumentation , Adolescent , Cuspid/pathology , Dental Alloys , Diastema/therapy , Elasticity , Female , Humans , Incisor/pathology , Male , Malocclusion/therapy , Models, Dental , Nickel , Orthodontic Anchorage Procedures/instrumentation , Orthodontic Retainers , Patient Care Planning , Patient Selection , Stress, Mechanical , Titanium , Young AdultABSTRACT
UNLABELLED: The Inman Aligner is a highly effective and unique evolution of the traditional spring retainer that uses super-elastic Nickel-Titanium open coil springs to move upper and lower anterior teeth with light but consistent forces, enabling correction of anterior crowding, rotations and some types of spacing. CLINICAL RELEVANCE: This article describes the appliance, its uses and limitations.
