M I Srebniak1, M Joosten1, M F C M Knapen2,3, L R Arends4,5, M Polak4, S van Veen1, A T J I Go2, D Van Opstal1. 1. Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands. 2. Department of Obstetrics and Gynecology, Erasmus MC, Rotterdam, The Netherlands. 3. Foundation Prenatal Screening Southwest Region of the Netherlands, Rotterdam, The Netherlands. 4. Department of Psychology, Education & Child Studies (DPECS), Erasmus University Rotterdam, Rotterdam, The Netherlands. 5. Department of Biostatistics, Erasmus MC, Rotterdam, The Netherlands.
Abstract
OBJECTIVE: To establish, based on a systematic literature review, the frequency of pathogenic submicroscopic chromosomal aberrations in fetuses that are not at increased risk for unbalanced structural chromosomal aberrations, with the aim of determining whether high-resolution testing for submicroscopic aberrations is beneficial in a general pregnant population. METHODS: EMBASE, PubMed, Web of Science and CENTRAL databases were searched systematically on 3 June 2016 for all relevant articles on the prevalence of pathogenic submicroscopic copy number variants (CNVs) in fetuses referred for prenatal invasive testing because of advanced maternal age (AMA) or parental anxiety (ANX). Relevant full-text articles were analyzed and the prevalence of submicroscopic CNVs was calculated based on the extracted data. Meta-analysis was conducted in a pooled cohort of 10 614 fetuses based on the 10 largest studies (n > 300) of a total of 19 that were relevant. RESULTS: Pooled estimate analysis indicated that 0.84% (95% CI, 0.55-1.30%) of fetuses that had invasive testing because of AMA/ANX carried a pathogenic clinically significant submicroscopic aberration. The onset/penetrance of submicroscopic findings was studied in 10 314 fetuses reported in eight papers that presented aberrant cases with all necessary details to allow assessment of the findings. The pooled estimates resulting from meta-analysis of the data indicated that an early-onset syndromic disorder was detected in 0.37% (95% CI, 0.27-0.52%) of cases, a susceptibility CNV was found in 0.30% (95% CI, 0.14-0.67%) and late-onset diseases were reported in 0.11% (95% CI, 0.05%-0.21%). The prevalence of early-onset syndromic disorders caused by a submicroscopic aberration was calculated to be 1:270. When the risk for submicroscopic aberrations is added to the individual risk for microscopic chromosomal aberrations, all pregnant women have a risk of higher than 1 in 180 for a relevant chromosomal aberration, and pregnant women under 36 years of age have a higher risk for submicroscopic pathogenic aberrations than for Down syndrome. CONCLUSION: This systematic review shows that a significant proportion of fetuses in a general pregnant population carry a submicroscopic pathogenic CNV. Based on these figures, all women should be informed on their individual risk for all pathogenic chromosomal aberrations and not only for common trisomies.
OBJECTIVE: To establish, based on a systematic literature review, the frequency of pathogenic submicroscopic chromosomal aberrations in fetuses that are not at increased risk for unbalanced structural chromosomal aberrations, with the aim of determining whether high-resolution testing for submicroscopic aberrations is beneficial in a general pregnant population. METHODS: EMBASE, PubMed, Web of Science and CENTRAL databases were searched systematically on 3 June 2016 for all relevant articles on the prevalence of pathogenic submicroscopic copy number variants (CNVs) in fetuses referred for prenatal invasive testing because of advanced maternal age (AMA) or parental anxiety (ANX). Relevant full-text articles were analyzed and the prevalence of submicroscopic CNVs was calculated based on the extracted data. Meta-analysis was conducted in a pooled cohort of 10 614 fetuses based on the 10 largest studies (n > 300) of a total of 19 that were relevant. RESULTS: Pooled estimate analysis indicated that 0.84% (95% CI, 0.55-1.30%) of fetuses that had invasive testing because of AMA/ANX carried a pathogenic clinically significant submicroscopic aberration. The onset/penetrance of submicroscopic findings was studied in 10 314 fetuses reported in eight papers that presented aberrant cases with all necessary details to allow assessment of the findings. The pooled estimates resulting from meta-analysis of the data indicated that an early-onset syndromic disorder was detected in 0.37% (95% CI, 0.27-0.52%) of cases, a susceptibility CNV was found in 0.30% (95% CI, 0.14-0.67%) and late-onset diseases were reported in 0.11% (95% CI, 0.05%-0.21%). The prevalence of early-onset syndromic disorders caused by a submicroscopic aberration was calculated to be 1:270. When the risk for submicroscopic aberrations is added to the individual risk for microscopic chromosomal aberrations, all pregnant women have a risk of higher than 1 in 180 for a relevant chromosomal aberration, and pregnant women under 36 years of age have a higher risk for submicroscopic pathogenic aberrations than for Down syndrome. CONCLUSION: This systematic review shows that a significant proportion of fetuses in a general pregnant population carry a submicroscopic pathogenic CNV. Based on these figures, all women should be informed on their individual risk for all pathogenic chromosomal aberrations and not only for common trisomies.
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Authors: Jane L Halliday; Cecile Muller; Taryn Charles; Fiona Norris; Joanne Kennedy; Sharon Lewis; Bettina Meiser; Susan Donath; Zornitza Stark; George McGillivray; Melody Menezes; Sian K Smith; Della Forster; Susan Walker; Mark Pertile; David J Amor Journal: Eur J Hum Genet Date: 2018-02-06 Impact factor: 4.246
Authors: Olav B Petersen; Eric Smith; Diane Van Opstal; Marike Polak; Maarten F C M Knapen; Karin E M Diderich; Caterina M Bilardo; Lidia R Arends; Ida Vogel; Malgorzata I Srebniak Journal: Acta Obstet Gynecol Scand Date: 2020-05-12 Impact factor: 3.636
Authors: Malgorzata I Srebniak; Maarten F C M Knapen; Lutgarde C P Govaerts; Marike Polak; Marieke Joosten; Karin E M Diderich; Laura J C M van Zutven; Krista A K E Prinsen; Sam Riedijk; Attie T J I Go; Robert-Jan H Galjaard; Lies H Hoefsloot; Diane Van Opstal Journal: Mol Genet Genomic Med Date: 2019-12-01 Impact factor: 2.183