Prenatal diagnosis for fetuses with isolated and non-isolated congenital heart defects using chromosomal microarray and exome sequencing

Objective To investigate the use of chromosomal microarray (CMA) and Exome sequencing (ES) in fetuses with congenital heart disease (CHD). Methods The Fetal Medicine Unit of Shanghai First Maternity and Infant Hospital records were reviewed to ascertain all cases diagnosed with CHD by level 2 ultrasound examination between 2016 and 2019. Cases were categorized as isolated or associated with other abnormalities or fetal growth restriction. CMA was offered to all cases as a first-line genetic test followed by ES when CMA was non-diagnostic. Results Of the 586 ascertained, 84 (14.3%) had causative CMA abnormality, of which 8.8% (35/400) were in fetuses with isolated CHD and 26.3% (49/186) in those with other abnormalities. ES was performed in 47 cases with a negative CMA. Causative variants were identified in two (10.5%, 2/19) isolated cases and four(14.3%, 4/28) with other abnormalities. Conclusion Invasive procedures with CMA should be offered in pregnancies complicated by both non-isolated and isolated cardiac abnormalities. When CMA is not diagnostic, ES can add diagnostic value in both groups and should be considered even for fetuses with an isolated CHD.

Automated summary

This study investigated the use of chromosomal microarray (CMA) and exome sequencing (ES) in fetuses with congenital heart disease (CHD). The results showed that CMA should be offered as a first-line genetic test in pregnancies complicated by both isolated and non-isolated cardiac abnormalities. When CMA is non-diagnostic, ES can be considered to add diagnostic value.