After the promulgation of the first edition of expert consensus on the application of chromosomal microarray analysis (CMA) technology in prenatal diagnosis in 2014, after 8 years of clinical and technical development, CMA technology has become a first‑line diagnosis technology for fetal chromosome copy number deletion or duplication abnormalities, and is widely used in the field of prenatal diagnosis in China. However, with the development of the industry and the accumulation of experience in case diagnosis, the application of CMA technology in many important aspects of prenatal diagnosis, such as clinical diagnosis testimony, data analysis and genetic counseling before and after testing, needs to be further standardized and improved, so as to make the application of CMA technology more in line with clinical needs. The revision of the guideline was led by the National Prenatal Diagnostic Technical Expert Group, and several prenatal diagnostic institutions such as Peking Union Medical College Hospital were commissioned to write, discuss and revise the first draft, which was discussed and reviewed by all the experts of the National Prenatal Diagnostic Technical Expert Group, and was finally formed after extensive review and revision. This guideline is aimed at the important aspects of the application of CMA technology in prenatal diagnosis and clinical diagnosis, from the clinical application of evidence, test quality control, data analysis and interpretation, diagnosis report writing, genetic counseling before and after testing and other work specifications are elaborated and introduced in detail. It fully reflects the integrated experience, professional thinking and guidance of the current Chinese expert team on the prenatal diagnosis application of CMA technology. The compilation of the guideline for the application of CMA technology in prenatal diagnosis will strive to promote the standardization and advancement of prenatal diagnosis of fetal chromosome diseases in China.

After the promulgation of the first edition of expert consensus on the application of chromosomal microarray analysis (CMA) technology in prenatal diagnosis in 2014, after 8 years of clinical and technical development, CMA technology has become a first-line diagnosis technology for fetal chromosome copy number deletion or duplication abnormalities, and is widely used in the field of prenatal diagnosis in China. However, with the development of the industry and the accumulation of experience in case diagnosis, the application of CMA technology in many important aspects of prenatal diagnosis, such as clinical diagnosis testimony, data analysis and genetic counseling before and after testing, needs to be further standardized and improved, so as to make the application of CMA technology more in line with clinical needs. The revision of the guideline was led by the National Prenatal Diagnostic Technical Expert Group, and several prenatal diagnostic institutions such as Peking Union Medical College Hospital were commissioned to write, discuss and revise the first draft, which was discussed and reviewed by all the experts of the National Prenatal Diagnostic Technical Expert Group, and was finally formed after extensive review and revision. This guideline is aimed at the important aspects of the application of CMA technology in prenatal diagnosis and clinical diagnosis, from the clinical application of evidence, test quality control, data analysis and interpretation, diagnosis report writing, genetic counseling before and after testing and other work specifications are elaborated and introduced in detail. It fully reflects the integrated experience, professional thinking and guidance of the current Chinese expert team on the prenatal diagnosis application of CMA technology. The compilation of the guideline for the application of CMA technology in prenatal diagnosis will strive to promote the standardization and advancement of prenatal diagnosis of fetal chromosome diseases in China.
2014年我国第1版关于染色体微阵列分析（CMA）技术应用于产前诊断的专家共识发布后，经过8年余临床和技术发展的推动，CMA技术目前已经成为针对胎儿的染色体拷贝数缺失或重复异常的一线产前诊断技术，广泛应用于我国产前诊断领域。但随着行业的发展和诊断经验的积累，CMA技术临床应用的许多重要方面，如临床诊断指征、数据分析和检测前后遗传咨询等亟须进一步规范和提升，以使CMA技术的产前诊断应用更加符合临床的需求。本次修订工作由国家卫生健康委员会妇幼健康司批准成立的全国产前诊断专家组牵头，委托北京协和医院等数家产前诊断机构进行初稿的撰写和讨论修订，并经全国产前诊断专家组全体专家进行研讨和审查反馈，以及广泛函审修改后最终形成本指南。本指南针对CMA技术在产前诊断临床应用的重要方面，包括临床应用指征、检测的质量控制、数据的分析解读、诊断报告撰写、检测前后遗传咨询等工作的规范开展进行了详细的阐述和介绍，完整体现了当前中国专家团队对于CMA技术产前诊断应用的经验集成、专业思考和指导意见。本指南的编制将推动全国胎儿染色体及基因组疾病产前诊断工作的规范性和先进性得到进一步的提升。.

To evaluate genetic evaluation practices in newborns with the most common birth defect, congenital heart defects (CHD), we determined the prevalence and the yield of genetic evaluation across time and across patient subtypes, before and after implementation of institutional genetic testing guidelines.
This was a retrospective, cross-sectional study of 664 hospitalized newborns with CHD using multivariate analyses of genetic evaluation practices across time and patient subtypes.
Genetic testing guidelines for hospitalized newborns with CHD were implemented in 2014, and subsequently genetic testing increased (40% in 2013 and 75% in 2018, OR 5.02, 95% CI 2.84-8.88, P < .001) as did medical geneticists\' involvement (24% in 2013 and 64% in 2018, P < .001). In 2018, there was an increased use of chromosomal microarray (P < .001), gene panels (P = .016), and exome sequencing (P = .001). The testing yield was high (42%) and consistent across years and patient subtypes analyzed. Increased testing prevalence (P < .001) concomitant with consistent testing yield (P = .139) added an estimated 10 additional genetic diagnoses per year, reflecting a 29% increase.
In patients with CHD, yield of genetic testing was high. After implementing guidelines, genetic testing increased significantly and shifted to newer sequence-based methods. Increased use of genetic testing identified more patients with clinically important results with potential to impact patient care.

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Genomic diseases caused by pathogenic copy number variations (pCNVs) are a group of important causes for birth defects. At present, the methods used to detect CNV mainly include chromosomal microarray analysis (CMA) and copy number variation sequencing (CNV-seq) based on next generation sequencing (NGS). In recent years, CNV detection technology has been widely used in the field of prenatal diagnosis. To standardize the clinical application of such technologies, the authors have formulated a guideline for the application of CNV testing in prenatal diagnosis, which includes the basic requirement, scope of application, clinical testing and consultation, procedure of CNV analysis in prenatal diagnosis, with an aim to better serve the patients.

Fetal growth restriction can result from a variety of maternal, fetal, and placental conditions. It occurs in up to 10% of pregnancies and is a leading cause of infant morbidity and mortality. This complex obstetrical problem has disparate published diagnostic criteria, relatively low detection rates, and limited preventative and treatment options. The purpose of this Consult is to outline an evidence-based, standardized approach for the prenatal diagnosis and management of fetal growth restriction. The recommendations of the Society for Maternal-Fetal Medicine are as follows: (1) we recommend that fetal growth restriction be defined as an ultrasonographic estimated fetal weight or abdominal circumference below the 10th percentile for gestational age (GRADE 1B); (2) we recommend the use of population-based fetal growth references (such as Hadlock) in determining fetal weight percentiles (GRADE 1B); (3) we recommend against the use of low-molecular-weight heparin for the sole indication of prevention of recurrent fetal growth restriction (GRADE 1B); (4) we recommend against the use of sildenafil or activity restriction for in utero treatment of fetal growth restriction (GRADE 1B); (5) we recommend that a detailed obstetrical ultrasound examination (current procedural terminology code 76811) be performed with early-onset fetal growth restriction (<32 weeks of gestation) (GRADE 1B); (6) we recommend that women be offered fetal diagnostic testing, including chromosomal microarray analysis, when fetal growth restriction is detected and a fetal malformation, polyhydramnios, or both are also present regardless of gestational age (GRADE 1B); (7) we recommend that pregnant women be offered prenatal diagnostic testing with chromosomal microarray analysis when unexplained isolated fetal growth restriction is diagnosed at <32 weeks of gestation (GRADE 1C); (8) we recommend against screening for toxoplasmosis, rubella, or herpes in pregnancies with fetal growth restriction in the absence of other risk factors and recommend polymerase chain reaction for cytomegalovirus in women with unexplained fetal growth restriction who elect diagnostic testing with amniocentesis (GRADE 1C); (9) we recommend that once fetal growth restriction is diagnosed, serial umbilical artery Doppler assessment should be performed to assess for deterioration (GRADE 1C); (10) with decreased end-diastolic velocity (ie, flow ratios greater than the 95th percentile) or in pregnancies with severe fetal growth restriction (estimated fetal weight less than the third percentile), we suggest weekly umbilical artery Doppler evaluation (GRADE 2C); (11) we recommend Doppler assessment up to 2-3 times per week when umbilical artery absent end-diastolic velocity is detected (GRADE 1C); (12) in the setting of reversed end-diastolic velocity, we suggest hospitalization, administration of antenatal corticosteroids, heightened surveillance with cardiotocography at least 1-2 times per day, and consideration of delivery depending on the entire clinical picture and results of additional evaluation of fetal well-being (GRADE 2C); (13) we suggest that Doppler assessment of the ductus venosus, middle cerebral artery, or uterine artery not be used for routine clinical management of early- or late-onset fetal growth restriction (GRADE 2B); (14) we suggest weekly cardiotocography testing after viability for fetal growth restriction without absent/reversed end-diastolic velocity and that the frequency be increased when fetal growth restriction is complicated by absent/reversed end-diastolic velocity or other comorbidities or risk factors (GRADE 2C); (15) we recommend delivery at 37 weeks of gestation in pregnancies with fetal growth restriction and an umbilical artery Doppler waveform with decreased diastolic flow but without absent/reversed end-diastolic velocity or with severe fetal growth restriction with estimated fetal weight less than the third percentile (GRADE 1B); (16) we recommend delivery at 33-34 weeks of gestation for pregnancies with fetal growth restriction and absent end-diastolic velocity (GRADE 1B); (17) we recommend delivery at 30-32 weeks of gestation for pregnancies with fetal growth restriction and reversed end-diastolic velocity (GRADE 1B); (18) we suggest delivery at 38-39 weeks of gestation with fetal growth restriction when the estimated fetal weight is between the 3rd and 10th percentile and the umbilical artery Doppler is normal (GRADE 2C); (19) we suggest that for pregnancies with fetal growth restriction complicated by absent/reversed end-diastolic velocity, cesarean delivery should be considered based on the entire clinical scenario (GRADE 2C); (20) we recommend the use of antenatal corticosteroids if delivery is anticipated before 33 6/7 weeks of gestation or for pregnancies between 34 0/7 and 36 6/7 weeks of gestation in women without contraindications who are at risk of preterm delivery within 7 days and who have not received a prior course of antenatal corticosteroids (GRADE 1A); and (21) we recommend intrapartum magnesium sulfate for fetal and neonatal neuroprotection for women with pregnancies that are <32 weeks of gestation (GRADE 1A).

The detection of acquired copy-number abnormalities (CNAs) and copy-neutral loss of heterozygosity (CN-LOH) in neoplastic disorders by chromosomal microarray analysis (CMA) has significantly increased over the past few years with respect to both the number of laboratories utilizing this technology and the broader number of tumor types being assayed. This highlights the importance of standardizing the interpretation and reporting of acquired variants among laboratories. To address this need, a clinical laboratory-focused workgroup was established to draft recommendations for the interpretation and reporting of acquired CNAs and CN-LOH in neoplastic disorders. This project is a collaboration between the American College of Medical Genetics and Genomics (ACMG) and the Cancer Genomics Consortium (CGC). The recommendations put forth by the workgroup are based on literature review, empirical data, and expert consensus of the workgroup members. A four-tier evidence-based categorization system for acquired CNAs and CN-LOH was developed, which is based on the level of available evidence regarding their diagnostic, prognostic, and therapeutic relevance: tier 1, variants with strong clinical significance; tier 2, variants with some clinical significance; tier 3, clonal variants with no documented neoplastic disease association; and tier 4, benign or likely benign variants. These recommendations also provide a list of standardized definitions of terms used in the reporting of CMA findings, as well as a framework for the clinical reporting of acquired CNAs and CN-LOH, and recommendations for how to deal with suspected clinically significant germline variants.

Preeclampsia is a multifactorial disease with unknown pathogenesis. Even when recent studies explored this disease using several bioinformatics tools, the main objective was not directed to pathogenesis. Additionally, consensus prioritization was proved to be highly efficient in the recognition of genes-disease association. However, not information is available about the consensus ability to early recognize genes directly involved in pathogenesis. Therefore our aim in this study is to apply several theoretical approaches to explore preeclampsia; specifically those genes directly involved in the pathogenesis.
We firstly evaluated the consensus between 12 prioritization strategies to early recognize pathogenic genes related to preeclampsia. A communality analysis in the protein-protein interaction network of previously selected genes was done including further enrichment analysis. The enrichment analysis includes metabolic pathways as well as gene ontology. Microarray data was also collected and used in order to confirm our results or as a strategy to weight the previously enriched pathways.
The consensus prioritized gene list was rationally filtered to 476 genes using several criteria. The communality analysis showed an enrichment of communities connected with VEGF-signaling pathway. This pathway is also enriched considering the microarray data. Our result point to VEGF, FLT1 and KDR as relevant pathogenic genes, as well as those connected with NO metabolism.
Our results revealed that consensus strategy improve the detection and initial enrichment of pathogenic genes, at least in preeclampsia condition. Moreover the combination of the first percent of the prioritized genes with protein-protein interaction network followed by communality analysis reduces the gene space. This approach actually identifies well known genes related with pathogenesis. However, genes like HSP90, PAK2, CD247 and others included in the first 1% of the prioritized list need to be further explored in preeclampsia pathogenesis through experimental approaches.

BACKGROUND: The Society of Obstetricians and Gynecologists of Canada and the Canadian College of Medical Genetics published guidelines, in 2011, recommending replacement of karyotype with quantitative fluorescent polymerase chain reaction when prenatal testing is performed because of an increased risk of a common aneuploidy.
OBJECTIVE: This study\'s objective is to perform a cost analysis following the implementation of quantitative fluorescent polymerase chain reaction as a stand-alone test.
RESULTS: A total of 658 samples were received between 1 April 2014 and 31 August 2015: 576 amniocentesis samples and 82 chorionic villi sampling. A chromosome abnormality was identified in 14% (93/658) of the prenatal samples tested. The implementation of the 2011 Society of Obstetricians and Gynecologists of Canada and the Canadian College of Medical Genetics guidelines in Edmonton and Northern Alberta resulted in a cost savings of $46 295.80. The replacement of karyotype with chromosomal microarray for some indications would be associated with additional costs.
CONCLUSIONS: The implementation of new test methods may provide cost savings or added costs. Cost analysis is important to consider during the implementation of new guidelines or technologies. © 2017 John Wiley & Sons, Ltd.

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