Prenatal Diagnosis最新文献

{"title":"Genome Sequencing for All Pregnant Persons: Navigating the Next Frontier in Prenatal Diagnosis Through Patient Reflections.","authors":"Kristen E Kelly, Stephanie Galloway, Alexandra Demers, Amanda L Bergner, Jessica L Giordano","doi":"10.1002/pd.6884","DOIUrl":"https://doi.org/10.1002/pd.6884","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore participant reflections after receipt of prenatal genome sequencing (GS) results in the absence of fetal anomalies.</p><p><strong>Methods: </strong>Participants invited to complete a semi-structured interview consented to future research, were English speaking, and were between 30 days and 1 year since the conclusion of their sequenced pregnancy. A total of 18 interviews were conducted with 21 participants (3 couples interviewed concurrently) representing 15 unique pregnancies (81% term deliveries, 14% terminated pregnancies, and 5% preterm delivery). Interviews were transcribed, coded, and analyzed using a constructivist grounded theory approach.</p><p><strong>Results: </strong>Participants had various motivations for pursuing GS, yet all wanted maximal information. Almost all participants with positive results had downstream implications, including termination, cascade testing, referral to specialists, and changes in pregnancy management and neonatal care. Negative results provided reassurance for the pregnancy and child's early development. If available, most participants would pursue GS in a future pregnancy; however, a few raised concerns about cost and accessibility.</p><p><strong>Conclusion: </strong>Understanding the perspectives and needs of pregnant patients and their partners will help inform the implementation of GS as a first-tier prenatal diagnostic test.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Practical Prenatal Ultrasound Classification System for Lower Limb Anomalies-PRELLIM Classification.","authors":"Arda Arduç, Margriet H M van Doesburg, Melinda M E H Witbreuk, Merel C Van Maarle, Elisabeth van Leeuwen, Eva Pajkrt, Ingeborg H Linskens","doi":"10.1002/pd.6885","DOIUrl":"https://doi.org/10.1002/pd.6885","url":null,"abstract":"<p><strong>Objective: </strong>To address the current lack of a prenatal classification system for fetal lower limb anomalies, we developed and evaluated the PRELLIM (PREnatal Lower LIMb impairment) classification.</p><p><strong>Method: </strong>A systematic literature review was conducted to identify existing classifications. Based on sonographic features, we developed the PRELLIM classification and applied it to a retrospective cohort of fetuses with isolated lower limb anomalies assessed between 2007 and 2024 at Amsterdam UMC's fetal medicine unit.</p><p><strong>Results: </strong>No standardized prenatal classification system for lower limb anomalies was found. PRELLIM distinguishes isolated and non-isolated anomalies and categorizes them into clinically relevant subgroups (absent/short, duplication, fusion, contracture, bowing and other). It was applied to 643 fetuses with isolated lower limb anomalies. Contractures were most common (n = 599; 93.2%), followed by poly(syn)dactyly (n = 26; 4.0%), reduction defects (n = 9; 1.5%), bowing (n = 5; 0.8%), and a case of sirenomelia (0.1%). Three additional cases (0.4%) were classified as \"other\": two lymphangiomas and one amniotic band with lower leg constriction.</p><p><strong>Conclusion: </strong>PRELLIM is the first prenatal classification tailored to sonographically detectable lower limb anomalies. It aims to enhance diagnostic consistency, improve interdisciplinary communication, and support prenatal counseling and decision-making.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yield of Whole Genome Sequencing for Pathogenic Single Nucleotide Variants in Congenital Heart Disease: A Systematic Review and Meta-Analysis.","authors":"Hiba J Mustafa, Parisa Najjariasl, Faezeh Aghajani, Enaja V Sambatur, Andrew Rodenbarger, Stephanie Guseh, Amy E Roberts, Alireza A Shamshirsaz","doi":"10.1002/pd.6878","DOIUrl":"https://doi.org/10.1002/pd.6878","url":null,"abstract":"<p><strong>Objective: </strong>This systematic review and meta-analysis aimed to assess the diagnostic yield of pathogenic or likely pathogenic (P/LP) single nucleotide variants (SNVs) using whole genome sequencing (WGS) in congenital heart disease (CHD).</p><p><strong>Methods: </strong>A systematic search of three databases (2000-2024) was conducted, and two reviewers independently screened studies and extracted data following PRISMA and MOOSE guidelines. Pooled proportions were calculated using a random-effects model, and study quality was assessed using modified STARD criteria.</p><p><strong>Results: </strong>Fourteen studies were included, comprising 933 CHD cases, of which 165 had P/LP SNVs. The overall diagnostic yield of WGS for P/LP SNVs was 17.83%, with a yield of 9.83% in isolated CHD cases (without other abnormalities) and 22.36% in syndromic cases (with extracardiac anomalies, developmental abnormalities, or distinctive features). Among 105 cases from four studies with negative chromosomal microarray (CMA) results, 20 had subsequently positive findings by WGS, yielding a 20% incremental diagnostic benefit of WGS over CMA.</p><p><strong>Conclusions: </strong>These findings highlight the utility of WGS in identifying clinically relevant SNVs in CHD and suggest that WGS should be considered in the diagnostic workup of CHD, particularly in syndromic cases, to guide personalized management and multidisciplinary care.</p><p><strong>Prospero registration: </strong>CRD42025634370.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Prenatal Case of Focal Dermal Hypoplasia With Split Hand/Foot Malformation, Lack of Characteristic Skin Findings, Renal Agenesis, and Coloboma Due To a Novel PORCN Variant.","authors":"Molly Jackson, Ian Suchet, Kristopher Langdon, Rati Chadha, Weiming Yu, Elaine S Chan, Mary Ann Thomas","doi":"10.1002/pd.6880","DOIUrl":"https://doi.org/10.1002/pd.6880","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Controversies in Prenatal Diagnosis-Conference Debate 2024: All Fetuses Undergoing Fetal Therapy Should Have Exome Sequencing.","authors":"Teresa N Sparks, Rogelio Cruz Martinez, Tim Van Mieghem","doi":"10.1002/pd.6784","DOIUrl":"10.1002/pd.6784","url":null,"abstract":"<p><p>This manuscript summarises the debate held at the 2024 annual meeting of The International Society for Prenatal Diagnosis (ISPD). Experts discussed whether all fetuses undergoing fetal therapy should undergo exome sequencing. Arguments in favor included that, with increasing experience and better clinical availability, exome sequencing can yield valuable diagnostic and prognostic information beyond what is available from karyotyping and microarray. This additional information is often helpful in counseling parents and provides a better understanding of fetal conditions, allowing for personalised medicine and supporting advancements in disease-focused fetal therapies. On the contrary, however, significant concerns regarding availability and health equity were raised. Moreover, potential delays in care incurred by exome sequencing may negatively affect outcomes of fetal intervention. Finally, as the information gathered from genetic testing may or may not affect pregnancy management decisions beyond termination of pregnancy, many families may choose not to undertake testing. The arguments of both debaters document current controversies in exome sequencing and genetic testing in general. This was also reflected in a divided audience vote at the end of the debate.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1351-1358"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Utility and Yield of Carrier Exome Sequencing in High-Risk Indian Couples.","authors":"Mounika Endrakanti, Sarath R S, Neerja Gupta, Madhulika Kabra","doi":"10.1002/pd.6830","DOIUrl":"10.1002/pd.6830","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the diagnostic yield and spectrum of monogenic disorders identified through exome sequencing (ES) based couple carrier screening in high-risk couples.</p><p><strong>Methods: </strong>We retrospectively reviewed the results of carrier screening by ES conducted between 2016 and 2023 at a tertiary care center in India for couples at increased risk of inherited genetic disease in their children. After pre-test genetic counseling, all couples underwent carrier screening through ES. We defined high-risk couples as those at an increased risk of inherited genetic disease in their children, and classified them as Category I (couples with a significant obstetric history, such as a previous fetus or child with a suspected genetic disorder), Category II (couples with a family history of a suspected genetic disorder in a parent or close relative) and Category III (couples opting for expanded carrier screening without any significant contributory history). Category I was further subcategorized based on the phenotype of the affected fetus, neonate, or child into: Ia - multiple malformations including non-immune hydrops and skeletal dysplasia; Ib - features suggestive of other system involvement; Ic - neurological phenotype with or without intellectual disability; and Id - unexplained intrauterine/neonatal death or stillbirth.</p><p><strong>Results: </strong>Of the 137 couples evaluated, 130 (95%) belonged to category I, of which 48/130 (37%) were subcategorised as Ia, 61/130 (47%) as Ib, 8/130 (6%) as Ic and 24/130 (18.5%) as Id. Nine couples had more than one subcategory indication for ES. Four couples (3%) belonged to category II, and three (2%) belonged to category III. Consanguinity was noted in 23.4% (32/137). The overall diagnostic yield in the cohort was 38.7% (53/137), mainly contributed by category I (52/130, 40%), with the highest yield in subcategory Ib (39/61, 64%).</p><p><strong>Conclusion: </strong>Carrier screening by ES is useful for identifying couples at high risk of having an offspring with genetic disorders. The yield is higher in couples with an affected previous pregnancy. ES allows comprehensive carrier screening in genetically diverse populations.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1366-1371"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in Prenatal and Postnatal Phenotypic Evaluations in Patients With Congenital Anomalies and Known Genetic Diagnoses.","authors":"Nicole Horton, Leandra Tolusso, Kimberly Widmeyer, Hua He, Daniel T Swarr","doi":"10.1002/pd.6810","DOIUrl":"10.1002/pd.6810","url":null,"abstract":"<p><strong>Objectives: </strong>Gaps exist in the understanding of the presentation of genetic conditions across the lifespan, especially the prenatal period. This study describes the limitations of prenatal phenotyping among neonates with genetic conditions.</p><p><strong>Methods: </strong>We collected prenatal and postnatal phenotypes via retrospective chart review of neonates with genetic diagnoses who previously received fetal ultrasound, MRI, and echocardiogram at the Cincinnati Children's Fetal Care Center (CCFCC) between July 2018 and October 2022.</p><p><strong>Results: </strong>For 83 neonates with genetic diagnoses, the number of phenotypic findings significantly increased after postnatal evaluation (mean: 10.01) compared with what was identified during prenatal evaluation (mean: 4.65; p < 0.001). There was a significant increase in the number of anomalies noted postnatally in most body systems, including the musculoskeletal, nervous, and respiratory systems.</p><p><strong>Conclusions: </strong>There are significant increases in phenotypic findings prenatally and after birth. Fetuses with anomalies should be evaluated multiple times, particularly when a genetic etiology is suspected, to aid in phenotype-driven genetic testing. Identifying diagnoses during the prenatal period allows time for families to adapt perinatal medical management decisions or post-birth plans, such as adoption. Awareness of phenotypes that are difficult to evaluate may improve variant curation by placing less value in the absence of findings that may be characteristic of a disorder.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1281-1291"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Intersection Between Genetic Reproductive Carrier Screening and Genomic Newborn Screening: Implications for Clinical Practice.","authors":"Lilian Downie, Sebastian Lunke, Zornitza Stark","doi":"10.1002/pd.6771","DOIUrl":"10.1002/pd.6771","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1277-1280"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Exploration of Severe Mendelian Developmental Anomalies: Insights From Exome Sequencing Analyses in a Large Indian Cohort.","authors":"Neerja Gupta, Mounika Endrakanti, Rohit Sadanand, Kamal Naini, Vatsla Dadhwal, Manisha Jana, Aparna Sharma, Madhulika Kabra","doi":"10.1002/pd.6872","DOIUrl":"10.1002/pd.6872","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the diagnostic utility of exome sequencing (ES) in structurally abnormal fetuses and infants with suspected severe Mendelian developmental defects.</p><p><strong>Methods: </strong>This retrospective study included fetuses (≥ 12 weeks) and infants (≤ 6 months old) with suspected severe Mendelian disorders, clinically categorized as multiple malformations (MM), non-immune hydrops (NIH), and skeletal dysplasia (SKD). All subjects underwent detailed evaluation by a clinical geneticist, which included a clinical examination or fetal autopsy, as applicable, with parental consent. Based on the type of anomaly, investigations such as karyotype, chromosomal microarray (CMA), and/or proband exome sequencing (ES) were performed.</p><p><strong>Results: </strong>Ninety-seven unrelated subjects were enrolled, including 25 (25.8%) multiplex and 17 (17.5%) consanguineous families. They were categorized as multiple malformations (MM) (60/97), skeletal dysplasia (SKD) (19/97), and non-immune hydrops (NIH) (18/97), respectively. The CMA performed in 23 subjects was normal. The overall diagnostic yield of ES for pathogenic/likely pathogenic variants was 40.2% (39/97) and was higher in SKD (57.9%, 11/19), followed by NIH (44.4%, 8/18) and MM (33.3%, 20/60). Eighteen novel variants were identified in 16 genes in various categories. Additional findings on fetal autopsy helped in making a precise diagnosis in 8/21 (38%) subjects.</p><p><strong>Conclusion: </strong>This study elucidates the molecular basis of severe Mendelian developmental defects in early life. Proband-only ES helps in reaching a precise diagnosis in combination with deep phenotyping using fetal autopsy and has a good diagnostic yield. It could be used as a first-tier test, especially in resource-poor settings.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1220-1233"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing the Introduction and Implementation of Noninvasive Prenatal Testing (NIPT) in Japan, the Netherlands, and the United States: An Integrative Review.","authors":"Chloe Connor, Taisuke Sato, Diana W Bianchi, Kathleen Fenton, Elika Somani, Amy Turriff, Benjamin Berkman, Saskia Hendriks","doi":"10.1002/pd.6708","DOIUrl":"10.1002/pd.6708","url":null,"abstract":"<p><p>Previous studies suggest that NIPT's implementation differed widely across countries but offer limited insight into what shaped these differences. To address this gap, we conducted an in-depth analysis of how NIPT was incorporated into prenatal care in the US, the Netherlands, and Japan-countries with similar economic status-to identify actionable lessons. We conducted an integrative literature review on the process of introducing and implementing NIPT, stakeholders' roles, documented considerations in the decision to introduce NIPT, implementation choices, and NIPT uptake. We included 184 sources, including white and gray literature and non-English sources. We identified 17 considerations that were documented to have influenced the decision whether to introduce NIPT across five domains: clinical considerations, ethical considerations and societal values, financial considerations, demand and capacity and applicable oversight. Fewer factors seem to have been considered in the US as compared to Japan or the Netherlands. Countries subsequently made choices on how to implement NIPT-we identified 35 such choices. While most of the identified choices were eventually considered by all three countries, they made different decisions (e.g., on out-of-pocket costs). In 2022, the estimated proportion of pregnant persons who used NIPT was 58% in the Netherlands, 49% in the US, and 9% in Japan. While differences in cultural values, population characteristics, and healthcare systems explain some variation, we identified other more adaptable aspects of the decision-making process (e.g., oversight) that may be useful for countries introducing NIPT or similar technologies to consider.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1244-1264"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}