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.

Diagnostic Accuracy of Sentence Recall and Past Tense Measures for Identifying Children's Language Impairments.

Purpose Measures of linguistic processing and grammatical proficiency represent strong candidates for adaptation into language screeners for early elementary students. One key barrier, however, has been the lack of consensus around the preferred reference standard for assigning affected status. Diagnostic accuracies associated with sentence recall and past tense marking index measures were examined relative to 5 different reference standards of language impairment: receipt of language services, clinically significant levels of parental concern, low performance on language measures, a composite requiring at least 2 of these indicators, and a composite requiring convergence across all indicators. Method One thousand sixty grade K-3 students participated in school-based language screenings. All students who failed the screenings and a random sampling of those who passed were invited to participate in confirmatory assessments. The community-based sample was supplemented by a clinical sample of 58 students receiving services for language impairment. Two hundred fifty-four students participated in confirmatory testing. Examiners were naive to participants' status. Results Diagnostic accuracies for the sentence recall and past tense marking index measures varied across the different reference standards (areas under receiver operating characteristic curves: .67-.95). Higher levels of convergence occurred with reference standards based on behavioral measures. When affected status was defined by receipt of services and/or parental ratings, cases presented with higher levels of performance on the language measures than when affected status was based on behavioral criteria. Conclusion These results provide additional support for the adaptation of sentence recall and past tense marking to screen for language impairments in early elementary students. Supplemental Material https://doi.org/10.23641/asha.8285786.