The utility of nuchal translucency ultrasound in identifying rare chromosomal abnormalities not detectable by cell-free DNA screening.

Objective:: To evaluate the utility of nuchal translucency (NT) screening in the detection of rare chromosomal aneuploidies in the setting of cell-free DNA (cfDNA).

Methods:: A retrospective cohort study of pregnancies screened through the California Prenatal Screening Program between March 2009 and December 2012. Karyotype analysis was the primary method of chromosomal evaluation during the study period and abnormal chromosomal karyotype results were classified by whether the abnormality would be detectable by cfDNA (non-mosaic trisomy 13, 18, 21 or sex-chromosomal aneuploidy (SCA)). For those rare aneuploidies detectable by karyotype but not cfDNA, the number of cases that had an increased NT and the detection rate and positive predictive value (PPV) of increased NT for rare aneuploidies were determined.

Results:: A total of 452,901 pregnant women had screening. There were 2,572 chromosomally abnormal fetuses, of which 1,922 (74.7%) had a common aneuploidy detectable by cfDNA, leaving 450,979 without T13, 18, 21. Of these, 4,181 (0.93%) had an NT ≥ 3.0mm. There were 649 rare aneuploidies not detectable by cfDNA. Of these, 108 (16.6%) had an NT ≥3.0mm. The PPV of an NT ≥3.0mm for rare aneuploidies was 2.6%. In all, 4,176 fetuses need to be screened with NT to detect a rare aneuploidy.

Conclusions:: The addition of NT to cfDNA screening would detect 16.6% of rare aneuploidies. Increased NT has a low PPV for rare aneuploidies and a large number of women would need NT screening to detect each affected fetus.