Comparative Genomic Hybridization to Microarrays in Fetuses with High-Risk Prenatal Indications: Polish Experience with 7400 Pregnancies

Abstract

The aim of this study was to determine the suitability of the comparative genomic hybridization to microarray (aCGH) technique for prenatal diagnosis, but also to assess the frequency of chromosomal aberrations that may lead to fetal malformations but are not included in the diagnostic report. We present the results of the aCGH in a cohort of 7400 prenatal cases, indicated for invasive testing due to ultrasound abnormalities, high-risk for serum screening, thickened nuchal translucency, family history of genetic abnormalities or congenital abnormalities, and advanced maternal age (AMA). The overall chromosomal aberration detection rate was 27.2% (2010/7400), including 71.2% (1431/2010) of numerical aberrations and 28.8% (579/2010) of structural aberrations. Additionally, the detection rate of clinically significant copy number variants (CNVs) was 6.8% (505/7400) and 0.7% (57/7400) for variants of unknown clinical significance. The detection rate of clinically significant submicroscopic CNVs was 7.9% (334/4204) for fetuses with structural anomalies, 5.4% (18/336) in AMA, 3.1% (22/713) in the group of abnormal serum screening and 6.1% (131/2147) in other indications. Using the aCGH method, it was possible to assess the frequency of pathogenic chromosomal aberrations, of likely pathogenic and of uncertain clinical significance, in the groups of cases with different indications for an invasive test.

Prenatal Screening and Diagnostic Considerations for 22q11.2 Microdeletions

“…Genitourinary (GU) malformations are reported in 8-17% of 22q11.2DS pregnancies, and include pyelectasis and hydronephrosis, unilateral or rarely bilateral renal agenesis, unilateral multicystic dysplastic kidney, and ureterocele [6,11,38,39,41,54,55]. GU malformations were noted in 7.5% (6/80) of the pregnancies in the Kowalczyk et al series [48].…”

“…Cardiac malformations were the indication for diagnostic genetic testing in 59 of 80 patients with 22q11.2DS identified in previously unpublished prenatal data from a series using CMA at the Institute of Mother and Child, Warsaw, Poland, from 2014-2021 (Table 3) [48]. Of the cardiac anomalies reported, 49% (29/59) were ToF, 12% hypoplastic left heart syndrome (HLHS), and 19% a VSD (Table 3).…”

Prenatal Utility of Chromosomal Microarray Analysis and Pregnancy Outcomes ： A Cohort Study of 4211 Pregnancies

“…Clinical indications include only advanced maternal age (467/4211,11.09%), high-risk maternal serum screening (832/4211, 19.76%), high risk of NIPT (573/4211,13.6%), abnormal ultrasound (1379/4211, 32.75%) and other indications(960/4211,22.80%), such as intrauterine growth retardation, history of adverse pregnancy or family history, maternal request, in vitro fertilization, drug use or exposure to toxic substances during pregnancy, consanguineous marriage, and parental anxiety. The mean gestational age was 12 weeks (11)(12)(13) for chorionic villus and 20 weeks (16-30) for amniocentesis. ).…”

Clinical Application of Chromosomal Microarray Analysis in High-Risk Pregnancies

“…Nevertheless, for patients with microdeletion or microduplication and high-risk NIPT ndings, karyotyping alone was not be su cient as it could not detect additional CNVs, which was Along with UPD variations, this totals to a 10.5% diagnostic yield by both CMA and G-banding, which is similar to those reported in the literature. [22,23] Detection rate of UPD by CMA chromosomal segments resulting from complete or segmental chromosomal homozygosity, which may be a common nding in normal individuals. When the presence of ROH is restricted to a single autosome of ≥ 10 Mb, this region is likely an isodisomy due to an UPD event.…”