Our study aimed to examine the relevance of cell-free fetal DNA (cfDNA) testing on the screening of chromosomal defects and the issue of pregnancies in patients with a risk over 1:50 after the first-trimester combined test.

This is a retrospective monocentric study. We included all consecutive patients with a singleton pregnancy between January 2015 and December 2020 attending our fetal medicine center because the estimated risk for trisomy 21 after the first-trimester combined screening was over 1:50. The patients could either choose to have invasive testing or cell-free DNA testing. We collected data about the patient, the tests results (cfDNA, karyotype) and the pregnancy outcome (born alive, medical termination, miscarriage or intrauterine fetal death).

We included 98 patients with an estimated risk for trisomy 21 over 1:50. We found a total of 14 major chromosomal abnormalities (14/98; 14.3%), of which: thirteen trisomies 21 and one triploidy 69, XXY. A cfDNA testing was chosen by 34 (34/98; 34.7%) patients. Among the pathological results of invasive testing, 5 (5/64; 7.8%) couldn't be targeted by cfDNA testing. Two of them were placental mosaicism, one a triploidy 69, XXY, and two defects inherited from a parent and considered benign. There was no miscarriage linked to an invasive test in the population study.

In our monocentric cohort, a third of the patients choose cfDNA in a case of a risk over 1:50 after combined testing. Even if this cohort is too small to draw definitive conclusions, cfDNA could be safe in a high-risk population after combined testing. None of the chromosomal abnormalities found at the karyotype and non-detectable by cfDNA was a loss of information that impacted pregnancy follow-up. Further study could explore the input of Genome-Wide cfDNA and chromosomal micro-array in this population.