2018 ISPD Conference

Is cell-free DNA testing appropriate in fetuses with increased nuchal translucency?
Jezid Miranda1, Virginia Borobio2, Celia Badenas3, Laia Rodriguez-Revenga3, Antoni Borrell4

1Fetal i+D Fetal Medicine Research, BCNatal – Barcelona Center for Maternal-Fetal and Neonatal Medicine, Barcelona, Spain
2Department of Maternal-Fetal Medicine, Institute Gynecology, Obstetrics and Neonatology, Hospital Clínic Barcelona, Barcelona, Spain
3Hospital Clínic – Centro de Diagnóstico Biomédico – Bioquímica y Genética Molecular, Barcelona, Spain, Barcelona, Spain
4Department of Maternal-Fetal Medicine, Institute Gynecology, Obstetrics and Neonatology, Hospital Clinic of Barcelona, Barcelona, Spain
Objectives
Cell-free DNA is currently considered an advanced screening test, however, its utility in patients with an abnormal first-trimester ultrasound remains to be established. The objective of this study was to assess the frequency of atypical and submicroscopic chromosomal anomalies (not detectable using standard cell-free DNA testing), as well as fetal structural abnormalities observed at the first-trimester scan, in fetuses with an increased nuchal translucency (NT).
Methods
Prospective cohort study. From January 2013 to December 2017, 227 fetuses with an NT ≥ 99th centile at 11-13 weeks' gestation underwent genetic testing in chorionic villi by means of QF-PCR and chromosomal microarray analysis (CMA), in a clinical setting in which more than 95% of pregnant women receive first-trimester combined screening. The frequency of common, atypical and submicroscopic chromosomal anomalies (not detectable using standard cell-free DNA testing), as well as fetal structural abnormalities observed at the first-trimester scan, was determined in the study group. 
Results
In 67 cases (30%) common aneuploidies (involving chromosomes 13, 18, 21 or X) were identified. Among the remaining 160 fetuses that would receive a theoretical negative cell-free DNA, five (3.1%) had a clinically relevant atypical chromosomal anomaly (two triploidies, two mosaicisms, and one monosomy 5), and six (3.8%) had submicroscopic anomalies. Finally, among the 149 fetuses with normal QF-PCR and CMA, a major fetal malformation was observed in 16 (11%) fetuses at the early anomaly scan, and in 18 (12%) in the second or third trimester.
Conclusions
Cell-free DNA does not appear to be the appropriate genetic test in fetuses with a NT above the 99th centile, given that 6.9% of them will have a chromosomal anomaly not detectable with the current tests. Additionally, 11% of those fetuses will have a major structural abnormality identifiable using first-trimester ultrasound.