Prenatal Genome-Wide Cell-Free DNA Screening: Three Years of Clinical Experience in a Hospital Prenatal Diagnostic Unit in Spain

Autores de IIS La Fe

• Laia Pedrola Vidal

  Autor

• Mónica Pilar Roselló Piera

  Autor

• Carla Martín Grau

  Autor

• Juan Salvador Rubio Moll

  Autor

• Rosa Maria Gomez Portero

  Autor

• Beatriz Marcos Puig

  Autor

• José Vicente Cervera Zamora

  Autor

• Ramiro De La Cruz Quiroga

  Autor

• Carmen Orellana Alonso

  Autor

Grupos

• Hematología y Hemoterapia

• Investigación Traslacional en Genética

Abstract

Genome-wide prenatal cell-free DNA (cfDNA) screening can be used to screen for a wide range of fetal chromosomal anomalies in pregnant patients. In this study, we describe our clinical experience with a genome-wide cfDNA assay in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RAAs), and copy-number variations (CNVs) in about 6000 patients over a three-year period at our hospital's Prenatal Diagnostic Unit in Spain. Overall, 204 (3.3%) patients had a high-risk call, which included 76 trisomy 21, 21 trisomy 18, 7 trisomy 13, 29 SCAs, 31 RAAs, 31 CNVs, and 9 cases with multiple anomalies. The diagnostic outcomes were obtained for the high-risk cases when available, allowing for the calculation of positive predictive values (PPVs). Calculated PPVs were 95.9% for trisomy 21, 77.8% for trisomy 18, 66.7% for trisomy 13, 10.7% for RAAs, and 10.7% for CNVs. Pregnancy and birth outcomes were also collected for the majority of RAA and CNV cases. Adverse perinatal outcomes for some of these cases included preeclampsia, fetal growth restriction, preterm birth, reduced birth weight, and major congenital structural abnormalities. In conclusion, our study showed strong performance for genome-wide cfDNA screening in a large cohort of pregnancy patients in Spain.

Keywords

• prenatal cfDNA screening; genome-wide; rare autosomal aneuploidies; copy-number variations; trisomy