Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
Department of Obstetrics and Gynecology, Erasmus MC, Rotterdam, The Netherlands.
Ultrasound Obstet Gynecol. 2018 Apr;51(4):445-452. doi: 10.1002/uog.17533.
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.
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.
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.
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. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
通过系统文献回顾，确定非高危结构染色体异常胎儿的亚微观致病性染色体畸变的频率，以确定在一般孕妇人群中进行亚微观畸变的高分辨率检测是否有益。
于 2016 年 6 月 3 日，检索 EMBASE、PubMed、Web of Science 和 CENTRAL 数据库，以获取所有关于因高龄产妇（AMA）或父母焦虑（ANX）而接受产前有创性检测的胎儿亚微观拷贝数变异（CNV）致病性的相关文章。分析相关的全文文章，并根据提取的数据计算亚微观 CNV 的患病率。对 19 项相关研究中的 10 项最大研究（n > 300）进行了基于 10614 例胎儿的汇总队列荟萃分析。
汇总估计分析表明，因 AMA/ANX 接受有创性检测的胎儿中有 0.84%（95%CI，0.55-1.30%）携带致病性临床显著的亚微观异常。在 8 篇文章中报道了 10314 例存在亚微观发现的胎儿的起始/外显率研究，这些文章提供了所有必要的详细信息，以便评估这些发现。对数据进行荟萃分析的汇总估计表明，在 0.37%（95%CI，0.27-0.52%）的病例中检测到早发性综合征障碍，在 0.30%（95%CI，0.14-0.67%）中发现易感性 CNV，在 0.11%（95%CI，0.05%-0.21%）中报告了迟发性疾病。亚微观异常引起的早发性综合征疾病的患病率计算为 1:270。当将亚微观异常的风险添加到微观染色体异常的个体风险中时，所有孕妇发生相关染色体异常的风险均高于 1:180，而 36 岁以下孕妇的亚微观致病性异常风险高于唐氏综合征。
本系统综述表明，一般孕妇人群中相当一部分胎儿携带亚微观致病性 CNV。根据这些数据，应告知所有女性其所有致病性染色体异常的个体风险，而不仅仅是常见的三体。版权所有©2017 ISUOG。由 John Wiley & Sons Ltd 出版。
