• chromosomal microarray
• copy number variant
• karyotype
• prenatal diagnosis
• ultrasonography

• Chromosomal microarray analysis
• Karyotyping
• Prenatal diagnosis
• Variants of unknown significance

• Copy number variations
• Karyotyping
• Nasal bone absence
• Nasal bone hypoplasia
• Single nucleotide polymorphism array

• Humans
• Female
• Polymorphism, Single Nucleotide
• Pregnancy
• Retrospective Studies
• Nasal Bone/abnormalities
• Nasal Bone/diagnostic imaging
• Adult
• Karyotyping
• Ultrasonography, Prenatal
• Chromosome Aberrations/embryology
• Chromosome Aberrations/statistics & numerical data
• Maternal Age
• Chromosome Disorders/genetics
• Chromosome Disorders/diagnosis
• Chromosome Disorders/epidemiology
• DNA Copy Number Variations
• Prevalence
• Down Syndrome/genetics

• aneuploidies
• chromosomal aberrations
• clinical anomalies
• copy number variation sequencing
• pregnant Vietnamese women

• Humans
• Female
• Pregnancy
• DNA Copy Number Variations/genetics
• Chromosome Aberrations
• Vietnam
• Adult
• Retrospective Studies
• Fetus
• Prenatal Diagnosis/methods
• Aneuploidy
• Asian People/genetics
• Ultrasonography, Prenatal/methods
• Southeast Asian People

• Gene Solutions

• Pregnancy
• Female
• Humans
• Disclosure
• Penetrance
• Prenatal Diagnosis
• Prenatal Care
• Uncertainty

• 2015/82 Israel National Institute for Health Policy Research

• Pregnancy
• Female
• Humans
• Syndrome
• Prenatal Diagnosis
• Aneuploidy
• Cell-Free Nucleic Acids

• Chromosomal microarray analysis
• Copy number variant
• Prenatal diagnosis
• Variant of uncertain significance

• aCGH
• amniotic fluid
• array comparative genomic hybridization
• chorionic villi
• prenatal diagnosis

• Female
• Pregnancy
• Humans
• Chromosome Aberrations
• Microarray Analysis
• Phenotype
• Prenatal Diagnosis
• Vitamins

• CMA
• prenatal diagnosis
• skeletal dysplasia
• systematic review
• whole-exome sequencing

• 2021J01407 Fujian Provincial Natural Science Foundation

• Conflicts of interest
• Editorial process
• Peer review
• Resistance to change
• Technology advancement

• Amniotic fluid sample
• BoBs assay
• Karyotyping
• Prenatal diagnosis
• SNP array

• chromosomal abnormalities
• chromosomal microarray analysis
• genetic diagnosis
• next-generation sequencing
• prenatal array
• prenatal diagnosis
• ultrasound abnormalities

• Assisted reproductive technology
• Chromosomal microarray analysis
• DNA copy number variation
• Karyotyping
• Prenatal diagnosis

• CCD, charge coupled device
• DLC, diamond-like carbon
• Genetic analysis
• Medical care
• Microarray
• PCR, Polymerase chain reaction
• Screening test
• Surface treatment
• UGT, UDP-glucuronosyltransferase
• cfDNA, cell-free DNA
• ctDNA, circulating tumor DNA

• Single nucleotide polymorphism array
• copy number variation
• prenatal diagnosis
• prenatal ultrasound abnormality

• Amniocentesis
• Chorionic Villi Sampling
• Chromosome Aberrations
• Female
• Genetic Testing
• Humans
• Microarray Analysis
• Pregnancy
• Prenatal Diagnosis
• Retrospective Studies

• K12 HD001262 NICHD NIH HHS
• 5K12HD001262-18 NIH HHS

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.

• Fetal
• minor abnormalities
• whole-exome sequencing analysis

Congenital gastrointestinal obstruction (CGIO) mainly refers to the stenosis or atresia of any part from the esophagus to the anus and is one of the most common surgical causes in the neonatal period. The concept of genetic factors as an etiology of CGIO has been accepted, but investigations about CGIO have mainly focused on aneuploidy, and the focus has been on duodenal obstruction. The objective of this study was to evaluate the risk of chromosome aberrations (including numeric and structural aberrations) in different types of CGIO. A second objective was to assess the risk of abnormal CNVs detected by copy number variation sequencing (CNV-seq) in fetuses with different types of CGIO.

Data from pregnancies referred for invasive testing and CNV-seq due to sonographic diagnosis of fetal CGIO from 2015 to 2020 were obtained retrospectively from the computerized database. The rates of chromosome aberrations and abnormal CNV-seq findings for isolated CGIOs and complicated CGIOs and different types of CGIOs were calculated.

Of the 240 fetuses with CGIO that underwent karyotyping, the detection rate of karyotype abnormalities in complicated CGIO was significantly higher than that of the isolated group (33.8% vs. 10.8%, p < 0.01). Ninety-three cases with normal karyotypes further underwent CNV-seq, and CNV-seq revealed an incremental diagnostic value of 9.7% over conventional karyotyping. In addition, the incremental diagnostic yield of CNV-seq analysis in complicated CGIOs (20%) was higher than that in isolated CGIOs (4.8%), and the highest prevalence of pathogenic CNVs/likely pathogenic CNVs was found in the duodenal stenosis/atresia group (17.5%), followed by the anorectal malformation group (15.4%). The 13q deletion, 10q26 deletion, 4q24 deletion, and 2p24 might be additional genetic etiologies of duodenal stenosis/atresia.

The risk of pathogenic chromosomal abnormalities and CNVs increased in the complicated CGIO group compared to that in the isolated CGIO group, especially when fetuses presented duodenal obstruction (DO) and anorectal malformation. CNV-seq was recommended to detect submicroscopic chromosomal aberrations for DO and anorectal malformation when the karyotype was normal. The relationship between genotypes and phenotypes needs to be explored in the future to facilitate prenatal diagnosis of fetal CGIO and yield new clues into their etiologies.

• chromosomal microarray
• copy number variants
• fetal growth restriction
• karyotype
• prenatal diagnosis

• Adult
• Female
• Fetal Growth Retardation/genetics
• France
• Humans
• Microarray Analysis
• Pregnancy
• Prenatal Diagnosis
• Retrospective Studies

• chromosomal microarray analysis
• copy-number variant
• low-risk pregnancies
• prenatal diagnosis
• susceptibility locus

• Adult
• Chromosome Disorders/diagnosis
• Chromosome Disorders/embryology
• Chromosome Disorders/epidemiology
• DNA Copy Number Variations
• Female
• Humans
• Microarray Analysis/methods
• Microarray Analysis/statistics & numerical data
• Pregnancy
• Pregnancy Outcome/genetics
• Pregnancy, High-Risk/genetics
• Prenatal Diagnosis/methods
• Prevalence
• Ultrasonography, Prenatal/statistics & numerical data

Most studies on chromosomal microarray analysis (CMA) and amniocentesis risks have not evaluated pregnancies with low risk for genetic diseases; therefore, the efficacy and safety of CMA and amniocentesis in this population are unclear. This study aimed to examine the benefits and risks of prenatal genetic diagnostic tests in pregnancies having low risk for chromosomal diseases.

In this retrospective study, we used clinical data from a large database of 30,830 singleton pregnancies at gestational age 16–23 weeks who underwent amniocentesis for karyotyping with or without CMA. We collected socio-demographic, medical and obstetric information, along with prenatal screening, CMA and karyotyping results. Fetal loss events were also analysed. CMA was performed in 5,837 pregnancies with normal karyotype (CMA cohort). In this cohort, 4,174 women had normal prenatal screening results and the risk for identifying genetic abnormalities with >10% risk for intellectual disability by CMA was 1:102, with no significant difference between maternal age groups. The overall post-amniocentesis fetal loss rate was 1:1,401 for the entire cohort (n = 30,830) and 1:1,945 for the CMA cohort (n = 5,837). The main limitation of this study is the relatively short follow-up of 3 weeks, which may not have been sufficient for detecting all fetal loss events.

The low risk for post-amniocentesis fetal loss, compared to the rate of severe genetic abnormalities detected by CMA, suggests that even pregnant women with normal prenatal screening results should consider amniocentesis with CMA.

In pregnant women with advanced maternal age (AMA) and fetuses with ultrasonographic (USG) soft markers it is always challenging to decide whether to implement chromosomal microarray analysis (CMA) or not. It is unclear whether CMA should be used in the fetuses with isolated USG soft markers, and there is still a lack of extensive sample research.

We enrolled 1521 cases in our research and divided them into 3 groups as follows: pregnant women with isolated AMA (group 1, n=633), pregnant women whose fetuses had isolated USG soft markers (group 2, n=750), and pregnant women with AMA whose fetuses had isolated USG soft markers (group 3, n=138). All pregnant women underwent prenatal ultrasound and amniocentesis, and fetal cells in the amniotic fluid were used for genetic analysis of CMA. All participants signed a written informed consent prior to CMA.

Abnormal findings were detected by CMA in 330 (21.70%) fetuses, including 37 (2.43%) clinically significant copy number variations (CNVs), 52 (3.42%) benign or likely benign CNVs, and 240 (15.78%) variants of unknown significance. The frequency of clinically significant CNVs in group 1 and group 2 were significantly lower than that in group 3 (2.37% and 2.0% vs 5.07%, P<0.01). More than a half (59.46%, 22/37) of the pregnant women decided to continue their pregnancy despite having a fetus diagnosed with clinically significant CNV.

CMA can increase the diagnostic yield of fetal chromosomal abnormality for pregnant women with isolated AMA or/and their fetuses had isolated USG soft markers.

• CNV
• Microarray
• Microdeletions
• Microduplications
• Prenatal
• VOUS

• Indian Council of Medical Research

• Biallelic variants
• FBN2
• Severe CCA

• Array CGH
• CNV
• General cytogenetics
• Genetic counseling
• Pregnancy without ultrasound anomalies
• VOUS

• congenital abnormalities
• copy number variations
• microarray
• prenatal diagnosis
• ultrasonography

• Microarray
• prenatal
• variants of uncertain significance

• SNP
• cordocentesis
• cytogenetic abnormalities
• late trimester
• sonographic anomalies

• Abortion, Induced
• Adult
• Chromosome Aberrations
• Congenital Abnormalities/diagnosis
• Congenital Abnormalities/genetics
• Cordocentesis
• DNA Copy Number Variations
• Female
• Gene Dosage
• Genetic Predisposition to Disease
• Genetic Testing
• Humans
• Karyotype
• Karyotyping
• Middle Aged
• Polymorphism, Single Nucleotide
• Predictive Value of Tests
• Pregnancy
• Pregnancy Trimester, Third
• Prenatal Diagnosis
• Ultrasonography, Prenatal
• Young Adult

Invasive prenatal testing with chromosomal microarray analysis may be a relevant option for all pregnant women, but there is only moderate‐quality evidence for such an offer. We intended to study the prevalence of copy number variants (CNVs) in prenatal samples using a single SNP‐array platform stratified by indication.

A cross‐sectional study was performed based on a cohort. From January 2015 to December 2017, a total of 10 377 prenatal samples were received for prenatal single nucleotide polymorphism (SNP)‐array in the laboratory of the Genetics Generation Advancement Corporation. Indications for chromosomal microarray analysis studies included the confirmation of an abnormal karyotype, ultrasound abnormalities, advanced maternal age and parental anxiety. CNVs and region of homozygosity identified by the SNP‐array were analyzed.

Of 10 377 cases, 689 had ultrasound abnormalities and 9688 were ascertained to have other indications. The overall prevalence of CNVs was 2.1% (n = 223/10 377, 95% confidence interval [CI] 1.9‐2.4), but the prevalence was 4.4% (95% CI 3.0‐6.1) for cases referred with abnormal ultrasound findings and 2.0% (95% CI 1.7‐2.3) for other indications. Of the 223 CNVs detected, 42/10 377 were pathogenic (0.4%, 95% CI 0.3‐0.6), 84 were susceptibility CNV (0.8%, 95% CI 0.6‐1.0) and 97 were variants of uncertain significance (0.9%, 95% CI 0.8‐1.1). Using an SNP‐based platform allowed for the detection of paternal uniparental disomy of chromosome 14 in a fetus with ultrasound abnormality.

With an indication of advanced maternal age but normal ultrasound scans, the prevalence of pathogenic CNVs was 0.4% and that of susceptibility CNV 0.7%. As CNVs are independent of maternal age, the prevalence is likely the same for younger women. Thus, this study provides further evidence that chromosomal microarray analysis should be available for all women who wish to receive diagnostic testing, as this risk is above the cut‐off of 1:300 for Down syndrome, leading to the suggestion of invasive testing. A chromosomal microarray analysis based on SNP‐array platform is preferable, as it can also detect uniparental disomy in addition to copy number variants.

• abnormal ultrasound findings
• absence of heterozygosity
• copy number variant
• pathogenic CNV
• prenatal chromosomal microarray analysis
• variants of uncertain significance

• advanced maternal age
• chromosomal microarray analysis
• conventional karyotyping
• ultrasound abnormalities

• Abnormalities, Multiple/diagnostic imaging
• Abnormalities, Multiple/genetics
• Adult
• Female
• Humans
• Karyotyping
• Maternal Age
• Oligonucleotide Array Sequence Analysis/methods
• Pregnancy
• Prenatal Diagnosis/methods
• Retrospective Studies
• Ultrasonography, Prenatal

• No. 2017J01238 Natural Science Foundation of Fujian Province
• Natural Science Foundation of Fujian Province

Chromosomal microarray (CMA) has been shown to be cost-effective over karyotyping in invasive prenatal diagnosis for pregnancies with fetal ultrasound anomalies. Yet, information regarding preceding and subsequent tests must be considered as a whole before the true cost-effectiveness can emerge. Currently in Hong Kong, karyotyping is offered free as the standard prenatal test while genome-wide array comparative genome hybridization (aCGH), a form of CMA, is self-financed. A new algorithm was proposed to use aCGH following quantitative fluorescent polymerase chain reaction (QF-PCR) as primary test instead of karyotyping. This study aims to evaluate the cost-effectiveness of the proposed algorithm versus the current algorithm for prenatal diagnosis in Hong Kong.

Between November 2014 and February 2016, 129 pregnant women who required invasive prenatal diagnosis at two public hospitals in Hong Kong were prospectively recruited. The proposed algorithm was performed for all participants in this demonstration study. For the cost-effectiveness analysis, cost and outcome (diagnostic rate) data were compared with that of a hypothetical scenario representing the current algorithm. Further analysis was performed to incorporate women’s willingness-to-pay for the aCGH test. Impact of government subsidies on the aCGH test was explored as a sensitivity analysis.

The proposed algorithm dominated the current algorithm for prenatal diagnosis. Both algorithms were equally effective but the proposed algorithm was significantly cheaper (p ≤ 0.05). Taking into account women’s willingness-to-pay for an aCGH test, the proposed algorithm was more effective and less costly than the current algorithm. When the government subsidy reaches 100%, the maximum number of diagnoses could be made.

By switching to the proposed algorithm, cost saving can be achieved whilst maximizing the diagnostic rate for invasive prenatal diagnosis. It is recommended to implement aCGH as a primary test following QF-PCR to replace the majority of karyotyping for prenatal diagnosis in Hong Kong.

• Chromosomal microarray - prenatal diagnosis - cost effectiveness analysis - cost saving - Hong Kong
• Karyotyping

• Abnormal ultrasound findings
• chromosomal microarray analysis
• copy number variations
• genetic work-up
• termination of pregnancy

• ASCC1
• SMABF2
• arthrogryposis
• microdeletion

• AgNOR-staining
• C-banding
• Chromosomal heteromorphisms
• Chromosomal structural abnormality
• Prenatal diagnosis
• Recurrent spontaneous abortion

• Chromosomal aberrations
• Chromosomal microarray analysis (CMA)
• Single gene mutation
• Termination of pregnancy
• Trend

• chromosomal microarray
• prenatal diagnosis
• ventricular septal defect