First-trimester absent nasal bone: is it a predictive factor for pathogenic CNVs in the low-risk population?

To evaluate the association of first-trimester absent nasal bone (NB) and genetic abnormalities at G-banding karyotype and chromosomal microarray analysis (CMA) according to the nuchal translucency (NT) thickness.

This is a retrospective cohort study of fetuses that underwent the first-trimester scan for the combined test at 11⁺⁰ to 13⁺⁶ weeks' gestation. Invasive test with G-banding karyotype and/or CMA was performed based on the result of the combined test or if fetal defects were detected or for patient's choice, after genetic counseling. All cases with absent NB in the first and second trimester underwent a detailed anomaly scan with echocardiography in the second trimester, had a longitudinal ultrasound, and postnatal follow-up up to at least 1 year.

Between 2013 and 2018, 7228 women underwent the first-trimester scan at 11⁺⁰ to 13⁺⁶ weeks. Overall prevalence of absent NB was 1.3% (96/7228). Of those, in 86 pregnancies (1.2%), the absence of NB was confirmed also in the second trimester: 0.58% (40/6909) in the group with NT <95th centile; 6%(14/233) in the group with NT between 95 and 99th centile; and 37.2% (32/86) in the group with NT >99th centile, respectively. CMA pathogenic variants were found only in the group with NT >99th centile with a diagnostic yield of 9.4%. Fetuses with absent NB and NT between 95 and 99th centile had in 57% (8/14) a major chromosomal anomaly, while in the NT <95 centile group, there were 5% (2/40) of chromosomal abnormalities (one inherited from the father).

In the first trimester, the risk for genetic syndromes detectable by CMA is related mainly to the NT thickness rather than to the absence of NB per se. In fetuses with absent NB and NT >99th centile, CMA should be performed after karyotype analysis, while for NT between 95 and 99th centile, a karyotype should be proposed as first-line procedure. Data provided by our study may be helpful in counseling women/couples when an absent NB is identified in the first trimester.