First Trimester Screening for Common Trisomies and Microdeletion 22q11.2 Syndrome Using Cell-Free DNA: A Prospective Clinical Study.

Objectives: The aims of the study were to assess the false-positive and uninformative test rate with first trimester cell-free DNA (cfDNA) screening for common trisomies and microdeletion 22q11.2 (22q11.2DS) and to examine women's attitudes toward such an approach.

Methods: This is a prospective study at the Prenatal Medicine Department of the University of Tübingen, Germany, at 11-13 weeks. In all pregnancies, a detailed ultrasound examination was carried out, followed by a cfDNA analysis for common trisomies and 22q11.2DS. In cases where the cfDNA analysis indicated 22q11.2DS, invasive prenatal diagnostic testing and parental testing were performed. After delivery, a detailed neonatal clinical examination was carried out including further genetic testing. Prior to counselling about the study, we asked the pregnant women who were potentially eligible for the study to anonymously report on their knowledge about 22q11.2DS.

Results: A total of 1,127 pregnancies were included in the final analysis of the study. The first cfDNA test was uninformative in 15 (1.33%) pregnancies. In 10 (0.89%) cases, the test remained uninformative, even after the second blood sample. There were 3 (0.27%) cases with a positive cfDNA test for 22q11.2DS. In all, 983 women returned the anonymous questionnaire prior to study participation. Only 80 (8.1%) women responded that they felt familiar or very familiar with 22q11.2DS.

Conclusion: The addition of 22q11.2DS in first trimester cfDNA screening for common trisomies is feasible. The uninformative test rate for common trisomies and 22q11.2DS is 0.9%, and the false-positive rate for 22q11.2DS is 0.3%. Awareness and education around 22q11.2DS should be improved.