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Multicenter Study
. 2022 Dec;42(13):1575-1586.
doi: 10.1002/pd.6271. Epub 2022 Nov 30.

Positive predictive values and outcomes for uninformative cell-free DNA tests: An Italian multicentric Cytogenetic and cytogenomic Audit of diagnOstic testing (ICARO study)

Francesca Romana Grati  1 , Ilaria Bestetti  2   3 , Daria De Siero  1 , Francesca Malvestiti  1 , Nicoletta Villa  4 , Elena Sala  4 , Francesca Crosti  4 , Valentina Parisi  5 , Anna Maria Nardone  6 , Gianluca Di Giacomo  7 , Antonella Pettinari  8 , Giada Tortora  8 , Annamaria Montaldi  9 , Annapaola Calò  9 , Donatella Saccilotto  9 , Sara Zanchetti  9 , Paola Celli  9 , Silvana Guerneri  2 , Rosamaria Silipigni  2 , Laura Cardarelli  10 , Elisabetta Lippi  10 , Simona Cavani  11 , Michela Malacarne  11 , Rita Genesio  12 , Nicola Beltrami  13 , Maria Carla Pittalis  14 , Laura Desiderio  14 , Mattia Gentile  15 , Romina Ficarella  15 , Maria Paola Recalcati  16 , Ilaria Catusi  16 , Maria Garzo  16 , Lorena Miele  17 , Cecilia Corti  17 , Sara Ghezzo  18 , Veronica Bertini  19 , Francesca Cambi  19 , Angelo Valetto  19 , Barbara Facchinetti  20 , Laura Bernardini  21 , Anna Capalbo  21 , Federica Balducci  22 , Elisabetta Pelo  23 , Barbara Minuti  23 , Chiara Pescucci  23 , Costanza Giuliani  23 , Alessandra Renieri  24   25   26 , Ilaria Longo  26 , Rossella Tita  26 , Giuseppe Castello  26 , Rosario Casalone  27 , Rossana Righi  27 , Barbara Raso  28 , Alessandro Civolani  28 , Maria Cristina Muzi  28 , Manuela di Natale  28 , Luigia Varriale  29 , Daniela Gasperini  30 , Maria Cristina Nuzzi  31 , Angelo Cellamare  31 , Paola Casieri  31 , Rosa Busuito  32 , Caterina Ceccarini  33 , Carla Cesarano  33 , Orsola Privitera  34 , Daniela Melani  34 , Cristina Menozzi  35 , Cristina Falcinelli  35 , Olga Calabrese  35 , Paola Battaglia  36 , Antonella Tanzariello  36 , Tamara Stampalija  37   38 , Carmela Ardisia  39 , Paolo Gasparini  39 , Peter Benn  40 , Antonio Novelli  5
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Free article
Multicenter Study

Positive predictive values and outcomes for uninformative cell-free DNA tests: An Italian multicentric Cytogenetic and cytogenomic Audit of diagnOstic testing (ICARO study)

Francesca Romana Grati et al. Prenat Diagn. 2022 Dec.
Free article

Abstract

Objectives: To establish the positive predictive values (PPV) of cfDNA testing based on data from a nationwide survey of independent clinical cytogenetics laboratories.

Methods: Prenatal diagnostic test results obtained by Italian laboratories between 2013 and March 2020 were compiled for women with positive non-invasive prenatal tests (NIPT), without an NIPT result, and cases where there was sex discordancy between the NIPT and ultrasound. PPV and other summary data were reviewed.

Results: Diagnostic test results were collected for 1327 women with a positive NIPT. The highest PPVs were for Trisomy (T) 21 (624/671, 93%) and XYY (26/27, 96.3%), while rare autosomal trisomies (9/47, 19.1%) and recurrent microdeletions (8/55, 14.5%) had the lowest PPVs. PPVs for T21, T18, and T13 were significantly higher when diagnostic confirmation was carried out on chorionic villi (97.5%) compared to amniotic fluid (89.5%) (p < 0.001). In 19/139 (13.9%), of no result cases, a cytogenetic abnormality was detected. Follow-up genetic testing provided explanations for 3/6 cases with a fetal sex discordancy between NIPT and ultrasound.

Conclusions: NIPT PPVs differ across the conditions screened and the tissues studied in diagnostic testing. This variability, issues associated with fetal sex discordancy, and no results, illustrate the importance of pre- and post-test counselling.

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References

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