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.

ObjectiveTo 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.MethodMaternal 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.ResultsThe 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.ConclusionThe 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.

Since the introduction of cell-free DNA (cfDNA) based non-invasive prenatal testing (NIPT) over the last decade, numerous studies have reported on its screening performance in terms of detection rate and false-positive rate. 1 Another NIPT performance metric that is sometimes overlooked is the test failure (or no-call) rate. In addition to being confusing for the woman and physician receiving such a result, failures also negatively affect the actual sensitivity or detection rate of the test because a proportion of failures can be assumed to be trisomy cases. This can be illustrated by considering a hypothetical NIPT test with 100% Trisomy 21 (T21) detection rate at varying failure rates, similar to that previously presented by Yaron. 2 For a failure rate of 1%, 5%, or 10%, the corresponding actual detection rate of the screened population will deteriorate to 99%, 95%, and 90%, respectively, if

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The cover image is based on the Original Article Clinical validation of a novel automated cell‐free DNA screening assay for trisomies 21, 13, and 18 in maternal plasma by Olle Ericsson et al., https://doi.org//10.1002/pd.5528