Abstract
Background: Currently, a fetal nuchal translucency (NT) ≥ 99th percentile is an indication for invasive testing, often followed by chromosomal microarray analysis. However, there are no international guidelines for screening of NT between the 95th-99th percentiles.
Objective: To identify the chromosomal anomalies detected in the subgroup of NT between the 95th and 99th percentiles and to evaluate the accuracy of genome-wide cell-free DNA (cfDNA) testing for their detection.
Methods: This retrospective cohort study was performed at the Antenatal Diagnosis Unit in the Centre Hospitalier Universitaire (CHU) of Liège. Our cohort included all pregnancies with increased NT ≥ 95th percentile, that underwent invasive sampling using microarray analysis for genetic testing between January 2017 and December 2023. We compared the results of invasive testing with the expected results from genome-wide cfDNA analysis.
Results: Fifty-nine pregnancies were identified, with 40 exhibiting isolated increased NT between the 95th and 99th percentiles. Among these 40 fetuses, 6 were found to have chromosomal abnormalities detected by microarray analysis, including 4 with Trisomy 21 and 2 with microdeletions. Theoretically, at least one of these six abnormalities would not have been detected by cfDNA screening.
Conclusion: Our data suggest that in the subset of fetuses with mildly increased NT (95-99th percentiles), undergoing an invasive procedure with microarray analysis remains recommended due to a 15% (6/40) positive predictive value and if genome-wide cfDNA was performed instead at least one of the six anomalies would be missed. Our data suggest that 3 mm would be the best cut-off for invasive diagnostic testing. If a pregnant woman declines the invasive procedure, genome-wide cfDNA can be an alternative. However, it is important to inform the pregnant woman that even if the results of the cfDNA testing are normal, there still exists a residual risk for a chromosomal abnormality in the fetus.
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