Identification of copy number variations among fetuses with ultrasound soft markers using next-generation sequencing

Wang, Jing; Chen, Lin; Zhou, Cong; Wang, Li; Xie, Hong; Xiao, Yuanyuan; Yin, Daishu; Zeng, Yang; Tang, Feng; Yang, Yunyuan; Zhu, Hongmei; Chen, Xinlian; Zhu, Qian; Liu, Zhiying; Liu, Hongqian

doi:10.1038/s41598-018-26555-6

Cited by 31 publications

(46 citation statements)

References 31 publications

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“…The search revealed 799 studies, of which 9 studies in addition to our own study met the final inclusion criteria and were included in the meta-analysis (Figure 1). [18][19][20][21][22][23][24][25][26] Quality assessment of the included studies using QUADAS-2 was shown in Figure S1 of Supporting Information. Overall, 1817 fetuses were involved in this meta-analysis, including 405 fetuses with MVM and 1412 fetuses with other USMs (Table S3 of Supporting Information).…”

Section: Results Of Meta-analysismentioning

confidence: 99%

Should chromosomal microarray be offered to fetuses with ultrasonographic soft markers in second trimester: A prospective cohort study and meta‐analysis

Han

et al. 2020

Prenatal Diagnosis

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Objective: To evaluate whether chromosomal microarray (CMA) should be offered to fetuses with ultrasonographic soft markers (USMs) in the second trimester. Methods: A prospective cohort study and meta-analysis were conducted. In the prospective cohort study, 564 fetuses with USMs were enrolled. In the meta-analysis, eligible articles describing copy number variations in fetuses with USMs were included. Results: In the prospective cohort study, the diagnostic yields of CMA over noninvasive prenatal testing (NIPT) and karyotyping were significantly higher in fetuses with mild ventriculomegaly (MVM) than those in local control cohorts with normal ultrasound. However, the yields of CMA over NIPT and karyotyping in fetuses with other USMs were similar to controls. About ten studies, involving 405 fetuses with MVM and 1412 fetuses with other USMs, were included in the meta-analysis. The pooled diagnostic yields of CMA over NIPT and karyotyping in fetuses with MVM were 4.9% and 3.2%, respectively. In fetuses with other USMs, the yields of CMA over NIPT and karyotyping were 1.2% and 0.4%, respectively. Conclusion: It is reasonable to offer CMA as a first-tier test to fetuses with MVM. However, for fetuses with other USMs, the considerations to perform CMA should not differ from pregnancies with normal ultrasound. 1 | INTRODUCTION Ultrasound has become a crucial tool for the prenatal evaluation of growth and anatomy worldwide. 1 In China, a routine prenatal ultrasound is performed at 18 to 24 weeks gestational age for the detection of fetal anomalies and pregnancy complications and the majority of women choose to participate. 2 In addition to fetal structural abnormalities or abnormal fetal development, many other nonspecific, often transient anatomic findings, also known as "soft markers," can also be detected. 3,4 Although these soft markers are not anatomic abnormalities, there is evidence that they convey a statistically increased risk for fetal aneuploidy. 3,5 When ultrasonographic soft markers (USMs) are detected in second trimester, the finding can raise questions about prenatal diagnostic testing procedures. As technologies evolve, various methods are currently implemented in prenatal genetic testing, including noninvasive prenatal testing (NIPT) and invasive testing using karyotyping or chromosomal microarray (CMA). As compared to invasive testing, NIPT using cell-free fetal DNA (cffDNA) from maternal plasma is noninvasive and more acceptable by women. In contrast, invasive prenatal testing is performed by chorionic villi sampling, amniocentesis, or cord blood sampling, which is associated with an increased risk of miscarriage and other side-effects. 6 Karyotyping using the cells obtained from invasive testing is the conventional cytogenetic test with a

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Section: Results Of Meta-analysismentioning

confidence: 99%

Should chromosomal microarray be offered to fetuses with ultrasonographic soft markers in second trimester: A prospective cohort study and meta‐analysis

Han

et al. 2020

Prenatal Diagnosis

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“…One of the strengths of our study is that we are one of the few studies to examine the association between CMA aberration and USM in the United States (US). Wang et al were among the first to examine the association between pathogenic CNV and USM [11]. However, the study was conducted in the Chinese population.…”

Section: Resultsmentioning

confidence: 99%

A Retrospective Review of Copy Number Variants and Ultrasound-Detected Soft Markers

Angras¹,

Bailey²,

Singh³

et al. 2020

jmgm

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Objective: To examine the association of copy number variants (CNV) among fetuses with ultrasound-detected soft markers (USM). Methods: This IRB-approved retrospective cohort study of fetuses with prenatal or children with postnatal chromosomal microarray analysis (CMA) sought to examine an association between clinically relevant CNV (classified as pathogenic CNV or variants of uncertain significance (VUS)) and USM in women w ho delivered at Geisinger between January 2010 and July 2018. The following USM were evaluated: choroid plexus cyst, thickened nuchal fold, absent or hypoplastic nasal bone, echogenic intracardiac focus, echogenic bowel, short long bones, and urinary tract dilation. Fetuses or children with known aneuploidy or a single gene disorder were excluded. Odds ratios (OR) of the association between CNV and USM were reported along with associated 95% confidence intervals (CI) and p-values. P values <0.05 were considered significant. Results: Of the 348 fetuses/children, 89 (25.6%) had a clinically relevant CNV. Similar percentages of demographic, delivery and neonate characteristics were noted for those with a clinically relevant CNV and those with a normal microarray analysis. No statistically significant differences were noted am ong those fetuses/children with a clinically relevant CNV and structural anomaly (p = 0.52; OR 1.18, 95% CI 0.72-1.92), presence of one USM (p = 0.72; OR 1.52, 95% CI 0.79-2.92), or presence of more than one USM (p = 0.79; OR 1.56, 95% CI 0.28-8.72). Conclusion: Our data supports a lack of association between a clinically relevant copy number variant and an ultrasound-detected soft marker. A small statistically insignificant increase in odds of a clinically relevant CNV was noted for those fetuses/children with one or more USM.

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“…However, the diagnostic yield of CNVs in fetuses with isolated ANH remains uncertain. Some studies have reported the overall detection rates of pathogenic CNVs varied from 3.2-9% in fetuses with ANH and 4.5% of fetuses with isolated ANH [7][8][9] [10] (Table 4). In our study, CMA revealed the clinically signi cant CNVs (pathogenic and likely pathogenic) of 11.9% (10/84) in fetuses with isolated severe ANH, including pathogenic CNVs of 3.5% (3/84), similar to that in previous reports.…”

Section: Diagnostic Yield Of Cma Testing For Fetuses With Anhmentioning

confidence: 99%

“…In the prenatal domain, the isolated fetal pyelectasis during second-trimester targeted ultrasound was reported to be soft marker associated with trisomy 21 [6] . Meanwhile, several studies have described CNVs detected in fetuses with ANH [7] [8] [9] [10] . However, most of these cases were usually associated with additional ultrasound abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Chromosomal Abnormality in Fetuses with Isolated Antenatal Hydronephrosis: Update for Prenatal Diagnosis and Genetic Counseling

Zhou¹,

Yan²,

Meng³

et al. 2020

Preprint

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Background: The prenatal finding of fetuses with antenatal hydronephrosis (ANH) gives a significant dilemma for the clinicians. Which patients require invasive prenatal diagnosis? Though previous literatures have recommended the use of chromosomal microarray analysis (CMA)for fetuses with CAKUT, the cutoff value for CMA have no current consensus on fetuses with ANH. In this article, we aimed to detect chromosomal abnormalities in fetuses with isolated severe ANH (anterior-posterior renal pelvic diameter (APRPD) ≥ 10mm) by CMA, summarized the literatures and proposed recommendations for the prenatal genetic diagnosis according to APRPD.Methods: Fetuses (n=84) with isolated severe ANH (APRPD ≥ 10mm) were evaluated by CMA. According to APRPD measurements at second trimester, we classified the cases into two groups: (1) Group A: cases with APRPD of 10–15 mm(N=57); (2) Group B: cases with APRPD ≥ 15 mm(N=27).The prenatal and postnatal outcomes were assessed by ultrasonic examination and telephone follow-up.Results: Overall, one case with 18 trisomy was identified. Clinically significant copy number variants (pathogenic or likely pathogenic CNVs) were identified in 11.9% (10/84) cases, including 3.5% (3/84) of pathogenic CNVs. The detection rates were 5.2% (3/57), 25.9% (7/27) for group A and group B, respectively. There was statistically significant differences in the frequency of clinic significant CNVs in the two groups (p＜0.05). Conclusion: CMA is valuable in prenatal genetic diagnosis of fetuses with severe ANH（APRPD ≥ 10mm）, regardless of whether other ultrasonic abnormalities were observed. This cohort should be followed up during the pregnancy.

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Identification of copy number variations among fetuses with ultrasound soft markers using next-generation sequencing

Cited by 31 publications

References 31 publications

Should chromosomal microarray be offered to fetuses with ultrasonographic soft markers in second trimester: A prospective cohort study and meta‐analysis

Should chromosomal microarray be offered to fetuses with ultrasonographic soft markers in second trimester: A prospective cohort study and meta‐analysis

A Retrospective Review of Copy Number Variants and Ultrasound-Detected Soft Markers

Chromosomal Abnormality in Fetuses with Isolated Antenatal Hydronephrosis: Update for Prenatal Diagnosis and Genetic Counseling

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