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Chromosomal microarray analysis (CMA) is preferred for genetic work-up when fetal malformations are detected prenatally. To assess the detection rate of CMA after pregnancy termination due to abnormal ultrasound findings. CMA was successfully performed in 71 pregnancies using fetal DNA (mainly from skin) or placenta. Data regarding clinical background, pregnancy work-up, and CMA were analyzed. Findings were abnormal in 17 cases (23.9%), of which 13 were detectable by karyotype. The incremental yield of CMA was 4/71 (5.6%); 1/32 (3.1%) for cases with an isolated anomaly and 3/39 (7.7%) for cases with nonisolated anomalies. CMA yield from terminated pregnancies was 23.9%. Although most chromosomal abnormalities are detectable by karyotype, CMA does not require viable dividing cells; hence, it is more practical for work-up after termination. In most cases, the diagnosis was followed by consultation regarding the risk of recurrence and recommendations for testing in subsequent pregnancies. [ABSTRACT FROM AUTHOR]

Introduction: Duplication of the renal collecting system is one of the most common variants of urinary tract anatomy. The objective of our study was to examine the risk for chromosomal aberrations in this isolated prenatal sonographic finding. Methods: Data from all chromosomal microarray analyses (CMA) reported to the Ministry of Health between January 2013 and September 2017 were retrospectively obtained from a computerized database. All pregnancies with a sonographic diagnosis of the isolated duplex renal collecting system and documentation of CMA result were included. Rate of abnormal CMA findings was compared to the general population risk, based on a systematic review encompassing 9272 cases with normal ultrasound and a local data of 5541 pregnancies undergoing CMA due to maternal request. Results: Two pathogenic CMA finding was found amongst 143 pregnancies with double collecting system (1.4%), not significantly different from the risk for abnormal CMA results in the general population. In addition, five variants of unknown significance were demonstrated (3.5%). Conclusion: To our best knowledge, this analysis is the first report describing the rate of chromosomal anomalies in pregnancies with isolated duplex renal collecting system. Its results suggest that routine invasive prenatal testing with CMA analysis in such cases is no more useful than in the general population. Prospective well-adjusted studies are needed to guide the optimal management of these pregnancies. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated the yield of chromosomal microarray analysis in pregnancies complicated with fetal growth restriction (FGR) according to specific clinical parameters.Methods: The study was based on national records from the Israeli Ministry of Health. Chromosomal microarray analyses of amniocenteses performed nationwide for the indication of FGR, from January 2016 to March 2018, were included. The CMA yield was compared to 2 cohorts that reported the background risk.Results: Of 174 tests performed for the indication of FGR, there were 11 cases with a pathogenic/likely pathogenic result (6.3%). The yield of CMA was significantly higher in cases with major structural findings (29.4 vs. 3.4%, p = 0.001), compared to isolated FGR but not for minor structural findings (6.1 vs. 3.4%, p = 0.5). The rate of chromosomal aberrations was significantly higher for all cases with FGR, when compared to the background risk of a cohort of normal pregnancies (odds ratio [OR] 4.7, 95% CI 2.5-9 and OR 6.09, 95% CI 3.2-11.4) but not for isolated cases or cases diagnosed after 24 weeks of pregnancy.Conclusions: Chromosomal microarray analysis should be performed for all pregnancies complicated with FGR diagnosed before 24 weeks and for cases with major structural anomalies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To explore the risk for abnormal chromosomal microarray analysis (CMA) findings in pregnancies with oligohydramnios. Methods: Data from all CMA analyses performed due to oligohydramnios between 2013 and 2017 were retrospectively obtained from the Israeli Ministry of Health database. The rate of clinically significant (pathogenic and likely pathogenic) findings was compared to a local cohort of pregnancies with normal ultrasound, yielding a 1.4% rate of abnormal CMA results. In addition, a search was conducted through the PubMed database addressing the issue. Results: Fifty CMA analyses were performed due to oligohydramnios. The 2% risk for clinically significant CMA finding in pregnancies with oligohydramnios did not differ from the control population of 5541 pregnancies with normal ultrasound – relative risk (RR) 1.4 [95% confidence interval (CI) 0.2–10.2]. Literature search yielded 394 titles, of which four relevant articles were selected, all using fetal karyotyping. Conclusion: There is yet insufficient evidence to support invasive prenatal testing in pregnancies with isolated oligohydramnios. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to examine the frequency of abnormal Chromosomal Microarray (CMA) analyses among fetuses with isolated non-visualization of fetal gallbladder.Methods: Data from CMA analyses performed due to isolated non-visualization of fetal gallbladder between January 2013 and September 2016 were retrospectively acquired from a computerized database of the Israeli Ministry of Health. The results were compared with the rate for clinically significant CMA findings in general population, based on a large cohort of 5541 pregnancies undergoing CMA due to maternal request, and a systematic review of 9272 cases with normal ultrasound.Results: Of 45 pregnancies with isolated non-visualization of fetal gallbladder, CMA testing yielded one (2.22%) gain-of-copy-number variant at 16p11.2, categorized as "pathogenic". In addition, one finding of unknown significance was demonstrated. The risk for clinically meaningful CMA findings among pregnancies with isolated absent gallbladder was not significantly increased compared to control population.Conclusions: To the best of our knowledge, this study is the first report describing the rate of pathogenic CMA results in fetuses with isolated non-visualization of fetal gallbladder. The results, in conjunction with previous studies, show that the risk for abnormal CMA results in pregnancies diagnosed with non-visualized gallbladder is not significantly different from pregnancies with normal ultrasound. [ABSTRACT FROM AUTHOR]

Objective: To examine the risk for abnormal chromosomal microarray analysis (CMA) results among fetuses with an apparently isolated pelvic kidney. Methods: Data from all CMA analyses performed due to an isolated pelvic kidney reported to the Israeli Ministry of Health between January 2013 and September 2016 were retrospectively obtained. Risk estimation was performed comparing the rate of abnormal observed CMA findings to the general population risk, based on a systematic review encompassing 9272 cases and on local data of 5541 cases. Results: Of 120 pregnancies with an isolated pelvic kidney, two gain-of-copy number variants suggesting microduplication syndromes were demonstrated (1.67%). In addition, three variants of unknown significance were detected (2.5%). Conclusion: The risk for clinically significant CMA findings among pregnancies with an isolated single pelvic kidney was not significantly different compared to both control populations. The results of our study question the practice of routine CMA analysis in fetuses with an isolated pelvic kidney. [ABSTRACT FROM AUTHOR]

Objective: To determine the rate of chromosomal cytogenetic abnormalities in fetuses with late onset abnormal sonographic findings. Design: Retrospective cohort of women who underwent amniocentesis at or beyond 23 weeks of gestation, for fetal karyotype and chromosomal microarray analysis, indicated due to late onset abnormal sonographic findings. Results: All 103 fetuses had a normal karyotype. Ninety-five women also had chromosomal microarray analysis (CMA) performed. The detection rate of abnormal CMA (5/95, 5.3%) was similar to that of women who underwent amniocentesis due to abnormal early onset ultrasound findings detected at routine prenatal screening tests during the first or early second trimester (7.3%, P=0.46) and significantly higher than that for women who underwent amniocentesis and CMA upon request, without a medical indication for CMA (0.99%, P<0.0001). Conclusions: Late onset sonographic findings are an indication for amniocentesis, and if performed, CMA should be applied to evaluate fetuses with late onset abnormal sonographic findings. [ABSTRACT FROM AUTHOR]

Prenatal screening pathways, as nowadays offered in most Western countries consist of similar tests. First, a risk-assessment test for major aneuploides is offered to pregnant women. In case of an increased risk, invasive diagnostic tests, entailing a miscarriage risk, are offered. For decades, only conventional karyotyping was used for final diagnosis. Moreover, several foetal ultrasound scans are offered to detect major congenital anomalies, but the same scans also provide relevant information for optimal support of the pregnancy and the delivery. Recent developments in prenatal screening include the application of microarrays that allow for identifying a much broader range of abnomalities than karyotyping, and non-invasive prenatal testing ( NIPT) that enables reducing the number of invasive tests for aneuploidies considerably. In the future, broad NIPT may become possible and affordable. This article will briefly address the ethical issues raised by these technological developments. First, a safe NIPT may lead to routinisation and as such challenge the central issue of informed consent and the aim of prenatal screening: to offer opportunity for autonomous reproductive choice. Widening the scope of prenatal screening also raises the question to what extent 'reproductive autonomy' is meant to expand. Finally, if the same test is used for two different aims, namely detection of foetal anomalies and pregnancy-related problems, non-directive counselling can no longer be taken as a standard. Our broad outline of the ethical issues is meant as an introduction into the more detailed ethical discussions about prenatal screening in the other articles of this special issue. [ABSTRACT FROM AUTHOR]

ABSTRACT This retrospective cohort study aimed to define the optimal Regions of Homozygosity (ROH) size cut‐offs for prediction of morbidity, based on 13 483 Chromosomal Microarray Analyses (CMA). Receiver operating characteristic (ROC) curves were generated, and area under the curve (AUC) was used to assess the predictive capability of total ROH percentage (TRPS), ROH number and ROH segment size in distinguishing between healthy (n=6,196) and affected (n=6,839) cohorts. The metrics were examined for telomeric and interstitial segments, distinct TRPS categories, and across different ancestral origins. ROH segments were identified in 13 035 samples (96.7%), encompassing 66 710 ROH segments. Significant differences in TRPS and ROH segment size were observed between healthy and affected cohorts (p=0.012 and p < 0.001, respectively). However, no clinically significant thresholds could be established based on ROC curves for TRPS and ROH number per sample, as well as for ROH size (AUC 0.64, 0.55, and 0.62, respectively, Figure 1). The same was noted for telomeric versus interstitial locations, various origins, and subcategories of TRPS. In conclusion, this study highlights the complexity of ROH interpretation and emphasizes the importance of tailored reporting strategies in clinical practice. Our findings underscore the need for context‐specific reporting guidelines and further research, particularly in consanguineous populations. [ABSTRACT FROM AUTHOR]

This study investigates distal 2q13 microdeletion, presenting the largest cohort to date, including prenatal cases, alongside a comprehensive literature review. A retrospective analysis was conducted on distal 2q13 microdeletions from clinical charts and laboratory reports. The cohort was divided into "clinically indicated" and "not-clinically indicated" groups based on the reason for chromosomal microarray testing. Clinical cases from medical literature were reviewed and compared with our cohort. The study included 25 cases: 17 index patients and 8 family members, with 47% males and 53% females. Of these, 2 were postnatal and 15 were prenatal. In the "clinically indicated" group, 35% had abnormalities on prenatal ultrasound, while 65% in the "not-clinically indicated" group had no major anomalies. Inheritance was 50% paternal in the "clinically indicated" group, and in the "not-clinically indicated" group, 44% paternal, 22% maternal, and 33% de novo. Symptoms varied from asymptomatic to severe developmental issues. Literature review identified 51 postnatal cases, with intellectual disability, and dysmorphism being common features. Familial cases showed 20% de novo, 20% maternal, 21.5% paternal, and 40% unknown inheritance. Distal 2q13 microdeletion is linked to cognitive impairment risk and should be reported in test results based on parental preferences, requiring special considerations for clinical classification and reporting., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Chromosomal microarray analysis (CMA) is a technology used for the detection of clinically-significant microdeietions or duplications, with a high sensitivity for submicroscopic aberrations. It is able to detect changes as small as 5-10Kb in size - a resolution up to 1000 times higher than that of conventional karyotyping. CMA is used for uncovering copy number variants (CNVs) thought to play an important role in the pathogenesis of a variety of disorders, primarily neurodevelopmental disorders and congenital anomalies. CMA may be applied in the prenatal or postnatal setting, with unique benefits and limitations in each setting. The growing use of CMA makes it essential for practicing physicians to understand the principles of this technology and be aware of its powers and limitations.