AIM: To evaluate a conservative estimate of the prevalence of chromosome conditions in all fetuses and children with a major congenital heart defect (CHD) in Denmark between 2008 and 2018.

METHODS: This was a national register-based study including all singleton pregnancies with a pre- or postnatally diagnosed major CHD usually requiring surgery within the first year of life and a due date between July 2008 and December 2018 in Denmark. Data were retrieved from the Danish Fetal Medicine Database (DFMD) and the Danish Cytogenetic Central Register (DCCR) in the fall of 2020. The DCCR contains information on all prenatal and postnatal genetic analyses including karyotyping, chromosomal microarray, polymerase chain reaction, multiplex ligation-dependent probe amplification, and fluorescence in situ hybridization. All cases were reviewed by a clinical geneticist, and genetic changes were classified as pathogenic, likely pathogenic, uncertain significance, likely benign, and benign. Pathogenic and likely pathogenic were considered to be abnormal. Cases with a CHD without any registered chromosome analysis reported were considered genetically normal. Isolated CHD was defined as a case with a major CHD without any other structural malformations detected pre- or postnatally. Results were given as total numbers and frequencies. Comparison between isolated and non-isolated cases was performed using logistic regression analysis and presented as odds ratios (ORs) including 95% confidence intervals (CI).

RESULTS: We retrieved 8,482 cases with any cardiovascular diagnosis from the DFMD and excluded twins (n=112) and minor CHD (n=6,921), resulting in 1,449 cases with major CHD. Of the included cases, 917 (63.3%) had a chromosome analysis performed with an abnormal test result in 186 cases, resulting in a prevalence of chromosomal conditions of 12.8% (95% confidence interval 11.2;14.7) in cases with major CHD. The highest prevalences were found in cases with pulmonary atresia with an intact ventricular septum and in truncus arteriosus (28.6%), and the lowest in cases with transposition of the great arteries (TGA) (2.2%) and congenitally corrected transposition of the great arteries (0%). In isolated cases of TGA, the prevalence of chromosome conditions was 0.6%. The overall OR for a chromosome condition in non-isolated cases compared to isolated cases was 2.65 (95% CI 1.85;3.79).

CONCLUSIONS: We found an overall prevalence of chromosome conditions in cases with a major CHD of 12.8% in a national cohort with a high participation rate in 1st and 2nd -trimester screening, without including exome sequencing (ES) and whole exome sequencing (WES). The prevalences varied considerably according to CHD diagnosis and whether associated with extra-cardiac malformations. This knowledge is important in prenatal counseling. This article is protected by copyright. All rights reserved.