What have we learned from 691 prenatal chromosomal microarrays for ventricular septal defects?

Abstract

Introduction Ventricular septal defect (VSD) represents the most common type of congenital cardiac anomaly, affecting more than 1 in 300 live births. The objective of this study was to examine the incidence and nature of abnormal chromosomal microarray analysis (CMA) results in a large cohort of pregnancies with VSD. Material and methods Data acquisition was performed through the Ministry of Health computerized database. All CMA results performed due to VSD during 2013‐2017 were included. The rates of clinically significant CMA results of cases with isolated and non‐isolated VSD were compared with two control populations—a systematic review of 9272 pregnancies and a local cohort of 5541 fetuses with normal ultrasound. Results Overall, 691 CMA analyses performed due to a sonographic indication of VSD were detected. Of 568 pregnancies with isolated VSD, eight (1.4%) clinically significant copy number variants were detected, a nonsignificant difference compared with low risk pregnancies. Of the 123 pregnancies with non‐isolated VSDs, 18 (14.6%) clinically significant CMA results were detected, a considerably increased risk compared with control pregnancies. Karyotype‐detectable anomalies constituted 12 of the 18 abnormal CMA results in non‐isolated VSD group (66.7%), a significantly higher proportion compared with 2 of 8 (25%) in isolated VSD cohort. Conclusions The outcomes of our study, representing the largest number of CMA results in pregnancies with VSD, suggest that the rate of abnormal CMA findings in isolated VSD does not differ from pregnancies with normal ultrasound. This observation is true for populations undergoing routine common trisomy screening tests and early sonographic evaluation, as well as widely available non‐invasive prenatal screening. Conversely, CMA analysis yields a high detection rate in pregnancies with non‐isolated VSD. Our results question the recommendation to perform invasive prenatal testing for CMA in pregnancies with isolated VSD.

Prenatally detected isolated ventricular septum defects and the association with chromosomal aberrations—A nationwide register‐based study from Denmark

“…The correlation between VSDs and chromosomal aberrations has been a subject of interest and investigated thoroughly over the years 4,6‐8,10‐13,18 . However, the results vary greatly with reported prevalences ranging from 1.2% to 46.8% including both non‐isolated and isolated VSDs with different definitions of “isolated”.…”

“…However, the results vary greatly with reported prevalences ranging from 1.2% to 46.8% including both non‐isolated and isolated VSDs with different definitions of “isolated”. The studies investigating isolated VSDs have found risks of chromosomal aberrations to be between 1.2% and 5.5%, 7,8,10‐13 however, most studies were done in small populations. The largest study published by Maya et al in 2019 included 568 isolated VSDs with CMA results and found 8 cases with clinically significant abnormal copy number variants (1.4%), which they state is no different from the general population 12 .…”

“…The studies investigating isolated VSDs have found risks of chromosomal aberrations to be between 1.2% and 5.5%, 7,8,10‐13 however, most studies were done in small populations. The largest study published by Maya et al in 2019 included 568 isolated VSDs with CMA results and found 8 cases with clinically significant abnormal copy number variants (1.4%), which they state is no different from the general population 12 . Their results are similar to ours, as we found aberrations in 1.3% of cases with prenatally detected isolated VSDs when invasive tests were performed.…”

“…As a result, we need updated data regarding the risk for chromosomal abnormalities when counseling these women. More recent studies have investigated the association between isolated VSDs and chromosomal abnormalities, but the studies differ in inclusion criteria, hence results 6‐13 . Some of the studies did not exclude cases with other malformations and cases where second‐trimester soft markers were present, and some excluded cases with a high first‐trimester risk assessment.…”

“…More recent studies have investigated the association between isolated VSDs and chromosomal abnormalities, but the studies differ in inclusion criteria, hence results. [6][7][8][9][10][11][12][13] Some of the studies did not exclude cases with other malformations and cases where second-trimester soft markers were present, and some excluded cases with a high first-trimester risk assessment. Therefore, controversy remains regarding whether the fetuses with an isolated VSD and a low first-trimester risk for trisomy 21, 18 and, 13 are at higher risk of having a chromosome abnormality compared to the general population and whether the mothers should be offered prenatal invasive testing when an isolated VSD has been detected on a prenatal scan.…”