Risk of Clinically Significant Chromosomal Microarray Analysis Findings in Fetuses With Nuchal Translucency From 3.0 mm Through 3.4 mm.

Objective: To examine the risk of clinically significant chromosomal microarray analysis findings in fetuses with nuchal translucency from 3.0-3.4 mm. In addition, we aimed to define the yield of noninvasive prenatal testing (NIPT) in such pregnancies.

Methods: This retrospective cohort study included results of all chromosomal microarray analysis tests performed owing to a nuchal translucency measurement from 3.0-3.4 mm, without ultrasonographic anomalies, retrieved from the Israeli Ministry of Health computerized database. Rates of clinically significant (pathogenic and likely pathogenic) microarray findings were compared with a previously published local control population, encompassing 2,752 fetuses with normal ultrasound findings and nuchal translucency less than 3.0 mm.

Results: Overall, 619 chromosomal microarray analyses were performed owing to isolated nuchal translucency from 3.0-3.4 mm. Of these, 29 (4.7%) cases had clinically significant copy number variants, a significantly higher risk compared with control-group pregnancies (relative risk 3.3, 95% CI 2.6-7.2). Divided by tenths of millimeters, the risk for abnormal chromosomal microarray analysis findings remained significantly increased, except for the subgroup of 198 fetuses with nuchal translucency measurements of 3.0 mm. Noninvasive prenatal testing for the five common chromosome aneuploidies would have missed 41.4% of the abnormal copy number variants-1.9% of overall cases, or 1 in 52 fetuses with nuchal translucency from 3-3.4 mm. Genome-wide NIPT, as well as traditional karyotyping, could have missed an abnormal finding in 9 of 619 (1.5%), or 1 in 69 fetuses.

Conclusion: Our outcomes show that the rate of abnormal chromosomal microarray analysis findings in fetuses with nuchal translucency from 3.1-3.4 mm is significantly higher compared with fetuses with normal ultrasound findings.