A decade of change – lessons learned from prenatal diagnostics in Central Denmark region in 2008–2018

• Published in: Acta obstetricia et gynecologica Scandinavica Vol. 102; no. 11; pp. 1505 - 1510
• Main Authors: Lildballe, Dorte Launholt, Becher, Naja, Vestergaard, Else Marie, Christensen, Rikke, Lou, Stina, Sandager, Puk, Pedersen, Lars Henning, Gadsbøll, Kasper, Petersen, Olav Bjørn, Vogel, Ida
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-11-2023; John Wiley and Sons Inc
• Subjects: chromosomal aberrations; chromosomal microarray; clinical laboratory techniques; copy number variation; Diagnostic tests; Genetic disorders; interdisciplinary communication; Medical diagnosis; Original; Pregnancy; Prenatal care; Prenatal Diagnosis; prenatal screening; Denmark; chromosomal microarray; copy number variation; chromosomal aberrations; clinical laboratory techniques; interdisciplinary communication; prenatal diagnosis; prenatal screening
• ISSN: 0001-6349; 1600-0412
• DOI: 10.1111/aogs.14631

Introduction
In 2011, it was decided to implement chromosomal microarray in prenatal testing in the Central Denmark Region, mainly due to the expected higher diagnostic yield. Chromosomal microarray was introduced gradually for an increasing number of pregnancies and without a transition period where both karyotyping and chromosomal microarray were performed: first malformations (2011), then large nuchal translucency (2013), then high risk at combined first trimester risk screening (2016) and finally for all indications (2018). This retrospective study summarizes 11 years of using chromosomal microarray in invasive prenatal testing and presents the effect on diagnostic yield and turnaround time. Furthermore, the concerns when introducing chromosomal microarray are presented and discussed.
Material and methods
Registry data from the Danish Fetal Medicine Database, the regional fetal medicine database, the Danish Cytogenetic Central Register and the local laboratory database at Department of Clinical Genetics were all combined, and a cohort of 147 158 singleton pregnancies with at least one ultrasound examination was established
Results
Of the 147 158 pregnancies, invasive sampling was performed (chorionic villi or amniocytes) in 8456, corresponding to an overall invasive rate of 5.8%. Between 2016 and 2018, 3.4% (95% confidence interval [CI] 2.8–4.2%; n = 86) of the invasive samples (n = 2533) had a disease causing copy number variant and 5.3% (95% CI 4.4–6.2%; n = 133) had trisomies and other aneuploidies. The turnaround time more than halved from 14 days to an average of 5.5 days for chorionic villus sampling.
Conclusions
Chromosomal microarray identified 5.3% trisomies and 3.4% copy number variants, thereby increased the diagnostic yield by more than 64% compared with karyotype only and it also more than halved the turnaround time. Some preliminary concerns proved real, eg prenatal counseling complexity, but these have been resolved over time in a clinical path with expert consultations.
Diagnostic yield increased with 64% when pregnancies with indications high risk at first trimester screening and malformations were offered chromosomal microarray over karyotyping. A total of 1:481 pregnancies were diagnosed with a disease causing CNV when screened by cFTS and malformation scan in pregnancy.