In most European countries, if the risk of trisomy 21 exceeds 1/50, Women are offered further investigation through an invasive test. Since the development of the non-invasive test based on circulating free DNA from the entire genome (cfDNA), the use of non-invasive tests in this high-risk population is now being debated. Our study aims to investigate a cohort of women at high risk of isolated trisomy 21 with no ultrasound abnormalities at the first trimester ultrasound scan or nuchal translucency greater than the 99th percentile who underwent invasive sampling with chromosomal microarray analysis (CMA).

This retrospective cohort included 159 women with isolated high-risk of Trisomy 21 (T21) screening who underwent invasive testing with CMA between 2017 and 2023. We described chromosomal abnormalities and explored associations with first-trimester markers and ultrasound findings.

Chromosomal abnormalities were identified in 24% of cases (38/159), including twenty-seven trisomy 21, two trisomy 18, four true fetal mosaicisms (one trisomy 22, two trisomy 16, and one monosomy X), two cases of confined placental mosaicism (trisomy 22 and trisomy 13), and three copy number variants (two likely benign and one pathogenic). Low PAPP-A levels were significantly associated with chromosomal imbalance ( p < 0.001).

In a population of women with a high risk of trisomy 21 but without nuchal translucency greater than the 99th percentile or ultrasound signs at the first trimester, the rate of chromosomal abnormalities is 24%. Although these abnormalities are heterogeneous, the majority are aneuploidy; with only large CNVs of 13.9 Mb having a poor neurodevelopmental prognosis.