Abstract
BackgroundThis paper describes the clinical practice and performance of cell-free DNA sequencing-based non-invasive prenatal testing (NIPT) as a screening method for fetal trisomy 21, 18, and 13 (T21, T18, and T13) and sex chromosome aneuploidies (SCA) in a general Italian pregnancy population.MethodsThe AMES-accredited laboratory offers NIPT in maternal blood as a screening test for fetal T21, T18, T13 and SCA. Samples were sequenced on a NextSeq 550 (Illumina) using the VeriSeq NIPT Solution v1 assay.ResultsA retrospective analysis was performed on 36,456 consecutive maternal blood samples, including 35,650 singleton pregnancies, 800 twin pregnancies, and 6 triplet pregnancies. Samples were tested between April 2017 and September 2019. The cohort included 46% elevated-risk and 54% low-risk patients. A result indicative of a classic trisomy was found in 356 (1%) of singleton or twin samples: 254 T21, 69 T18, and 33 T13. In addition, 145 results (0.4%) were indicative of a SCA. Of the combined 501 screen-positive cases, 484 had confirmatory diagnostic testing. NIPT results were confirmed in 99.2% (247/249) of T21 cases, 91.2% (62/68) of T18 cases, 84.4% (27/32) of T13 cases, and 86.7% (117/135) of SCA cases. In the 35,955 cases reported as unaffected by a classic trisomy or SCA, no false negative cases were reported. Assuming that false negative results would be reported, the sensitivity of NIPT was 100.00% for T21 (95% Cl 98.47–100.0), T18 (95% Cl 94.17–100.0), and T13 (95% Cl 87.54–100.0). The specificities were 99.99% (95% Cl 99.98–100.0), 99.98% (95% Cl 99.96–100.0), 99.99% (95% Cl 99.97–100.0), and 99.95% (95% Cl 99.92–99.97) for T21, T18, T13, and SCA, respectively.ConclusionThis retrospective analysis of a large cohort of consecutive patients who had whole-genome sequencing-based NIPT for classic trisomies and SCA shows excellent detection rates and low false positive rates.
Highlights
This paper describes the clinical practice and performance of cell-free DNA sequencing-based noninvasive prenatal testing (NIPT) as a screening method for fetal trisomy 21, 18, and 13 (T21, T18, and T13) and sex chromosome aneuploidies (SCA) in a general Italian pregnancy population
In the case of an abnormal test result, additional counselling was provided by a clinical geneticist or obstetrician [19], and confirmatory testing in material obtained via amniocentesis or chorionic villus sampling was offered
Participants Between 18 April 2017 and 30 September 2019, 36,456 blood samples were sent for NIPT
Summary
This paper describes the clinical practice and performance of cell-free DNA sequencing-based noninvasive prenatal testing (NIPT) as a screening method for fetal trisomy 21, 18, and 13 (T21, T18, and T13) and sex chromosome aneuploidies (SCA) in a general Italian pregnancy population. The presence of circulating cell-free DNA (cfDNA) from the placenta in the maternal circulation was first demonstrated by Lo et al [4] This finding, combined with the discovery of massively parallel sequencing (MPS) technologies [5, 6], made it possible to develop a highly accurate noninvasive prenatal test (NIPT) for fetal aneuploidy detection, with a highly improved positive predictive value (PPV). This has allowed for a reduction in the number of invasive procedures and associated risks [7], as well as a reduction in the number of patients exposed to anxiety resulting from abnormal screening results [8]. As data on twin pregnancies are limited [15], the use of NIPT in twin and higher-order multiple pregnancies has been recommended with caution [16,17,18]
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