Is cell-free fetal DNA testing a safe option for women in a high-risk population after combined first-trimester testing?

Objectives: 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. Methods: 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). Results: 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. Conclusion: 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.(c) 2022 Elsevier Masson SAS. All rights reserved.