Prenatal Diagnosis最新文献

{"title":"Current Controversies in Prenatal Diagnosis 2: Conventional Postmortem Examination Remains the Gold Standard for the Anatomical Examination of Fetal Loss.","authors":"J Ciaran Hutchinson, Lorraine Potocki, Ignatia B Van den Veyver","doi":"10.1002/pd.6754","DOIUrl":"10.1002/pd.6754","url":null,"abstract":"<p><p>A comprehensive postmortem examination is an essential component of a work-up after stillbirth. Its findings can support accurate counseling of parents about causes and risk of recurrence. It also supports providers' decisions about most appropriate testing and management plans for future pregnancy to prevent recurrence. Informing parents about fetal autopsy and obtaining their consent is challenging, and conducting a fetal autopsy requires expertise that is, not universally available. Newer non-invasive or minimally invasive methods such as postmortem MRI and targeted biopsies can replace or supplement autopsies, but one must recognize that expertise in these methods is likewise not broadly available. This prompts the question whether a conventional postmortem examination should remain the gold standard for the anatomical examination of fetal loss. This report summarizes the \"for\" and \"against\" arguments made by two experts during a debate at the 28th International Conference on Prenatal Diagnosis and Therapy. Arguments favoring comprehensive fetal autopsy include the need to obtain the most complete and accurate information about the cause of the stillbirth. Arguments in favor of less invasive post-mortem examinations using other technologies include sufficiency in many instances and a more equitable and cost-effective approach to postmortem examination. While both debaters weighed the balance of these conflicting arguments differently, they agreed that more research in this area is needed.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1343-1350"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365429","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":"International Society for Prenatal Diagnosis 2024 Debate 3-Cytogenetics Is a Dinosaur and Should Be Replaced by Molecular Technologies.","authors":"Yassmine M N Akkari, Michael E Talkowski, Amy M Breman","doi":"10.1002/pd.6847","DOIUrl":"10.1002/pd.6847","url":null,"abstract":"<p><p>Cytogenetic technologies such as G-banding chromosome and FISH analyses have long been the gold standard diagnostic test in prenatal genetic testing. However, unbiased next-generation sequencing technologies such as fetal exome or genome sequencing (ES/GS) are becoming widely accessible and increasingly utilized, particularly for fetuses with structural anomalies. Emerging studies are now establishing increased diagnostic yields from molecular technologies, but there remains a lack of consensus as to whether ES/GS should replace cytogenetic technologies and targeted genepanel screening as first-line tests for all prenatal diagnoses. This report is a summary of the debate on this topic presented at the 28th International Conference on Prenatal Diagnosis and Fetal Therapy. Both expert debaters discussed the advantages and disadvantages.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1334-1342"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765317","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":"Highlights of the 28th ISPD Annual Conference, Hosted in Boston and Themed \"Envisioning Global Fetal-Maternal Genomics and the Paths to Treatment\".","authors":"Teresa N Sparks, Louise Wilkins-Haug","doi":"10.1002/pd.6875","DOIUrl":"10.1002/pd.6875","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1217-1219"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874849","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":"Going Back in Time: Prenatal Presentations of Postnatal Genetic Diagnoses Made in a Neonatal Intensive Care Unit.","authors":"Michael Duyzend, Malika Sud, Alissa M D'Gama, Tabitha Poorvu, Judy Estroff, Monica H Wojcik","doi":"10.1002/pd.6710","DOIUrl":"10.1002/pd.6710","url":null,"abstract":"<p><strong>Objectives: </strong>Prenatal genetic diagnosis can impact care across the perinatal continuum; however, prenatal suspicion for genetic disorders may be complicated by incomplete knowledge of fetal rare-disease phenotypes. Here, we describe the prenatal presentations of a cohort of infants with rare genetic conditions who were diagnosed postnatally in a neonatal intensive care unit (NICU), to characterize prenatal presenting features and evaluate why the diagnosis was not identified prenatally.</p><p><strong>Methods: </strong>Retrospective cohort study of infants born over a 7 year period (2017-2023) who were admitted to a Level IV NICU and received a postnatal genetic diagnosis prior to 1 year of age. We identified which of these infants had been imaged prenatally at our Maternal Fetal Care Center (MFCC) as an opportunity for prenatal genetic diagnosis. Clinical data were abstracted from the medical records.</p><p><strong>Results: </strong>51 cases met the inclusion criteria. Nine of the 51 infants were not strongly suspected to have a genetic syndrome prenatally when seen at the MFCC, as evidenced by lack of prenatal genetic consultation and lack of documented suspicion for a genetic etiology. These cases largely had absent or uncertain prenatal phenotypes. In most cases (42/51, 82.4%), prenatal diagnostic testing was not pursued even if offered. Overall, postnatal diagnoses, of which there was one dual diagnosis, were made by karyotype/FISH (11/52, 21.1%), microarray (8/52, 15.4%), gene panel/targeted testing (17/52, 32.7%), or exome sequencing (16/52, 30.8%).</p><p><strong>Conclusions: </strong>Our data illustrate the challenges in fetal phenotyping and support a broad approach to prenatal testing to facilitate early genetic diagnosis, which may meaningfully impact postnatal care.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1292-1312"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786776","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":"Reporting Criteria for Prenatally Identified Variants of Uncertain Significance Differs Among Cytogenetics Laboratories in North America.","authors":"Matthew A Shear, Arun P Wiita, Jingwei Yu, Brette Wayman, Teresa N Sparks, Mary E Norton, Kate Swanson","doi":"10.1002/pd.6785","DOIUrl":"10.1002/pd.6785","url":null,"abstract":"<p><strong>Objective: </strong>Current technical standards for chromosomal microarray (CMA) interpretation are not prescriptive for reporting variants of uncertain significance (VUS) identified prenatally. We sought to compare prenatal CMA reporting among cytogenetic labs and identify potential drivers of practice variation.</p><p><strong>Methods: </strong>We conducted an electronic cross-sectional survey of cytogeneticists in the United States and Canada from July-December 2023. Participants were identified through the American Cytogenetics Forum List.</p><p><strong>Results: </strong>Labs reported differences in their size threshold used when reporting CNVs lacking OMIM annotated genes as a VUS, variable use of clinical data such as ultrasound or family history when deciding to report a VUS, and differences in opinion regarding the underlying pathogenicity of certain CNVs. Many cytogeneticists reported concerns about legal liability related to prenatal CMA reporting, and many shared concerns that a patient may terminate a pregnancy based on a VUS.</p><p><strong>Conclusion: </strong>Reporting criteria for prenatally identified variants of uncertain significance differs among cytogenetic laboratories in North America. Many possible drivers of this practice variation were identified, including a lack of national guidelines that comprehensively address the unique considerations for prenatal CMA reporting.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1359-1365"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011851","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":"Single-Step Universal First-Trimester Cytomegalovirus Screening and Valacyclovir Prophylaxis in Pregnancy: A Cost-Utility Analysis in a High Seroprevalence Setting.","authors":"Zhi Zhen Lim, Clarence Ong, Ching Yee Chan, Kee Thai Yeo, Wei Yee Wan, Jerry Kok Yen Chan, Wei Ching Tan, Lay Kok Tan, Pamela Palasanthiran, Yi Wang, Liying Yang","doi":"10.1002/pd.6848","DOIUrl":"10.1002/pd.6848","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the cost-effectiveness of first trimester single-step universal cytomegalovirus (CMV) serological screening with valacyclovir as vertical transmission prophylaxis versus routine ultrasound-directed testing.</p><p><strong>Methods: </strong>A payer perspective cost-utility analysis was conducted on a hypothetical population of 100,000 pregnant women for a time horizon of 9 month of full-term pregnancy and the lifetime of children. Using a decision-tree and Markov model, we assessed quality-adjusted life years (QALYs) gained by preventing congenital CMV (cCMV) sequelae against the costs of universal screening and valacyclovir prophylaxis.</p><p><strong>Results: </strong>The ICER for universal screening strategy was USD125,864 (SGD170,087)/QALY-gained compared to routine ultrasound-directed testing. It prevented approximately 54 cCMV infections, 18 cases of symptomatic infections, and 17 cases of sensorineural hearing loss (SNHL) and cognitive impairment by age of 5 per 100,000 mothers screened. The primary factors influencing cost-effectiveness include the effectiveness of VCV in preventing vertical CMV transmission, the prevalence of primary CMV infection during pregnancy, the probability of symptomatic congenital CMV following periconceptional infection, and the cost of serological testing.</p><p><strong>Conclusions: </strong>Although the ICER of universal CMV screening appears high in absolute terms, it compares favorably with ICER of commonly offered antenatal screening methods such as first trimester non-invasive prenatal testing for women at intermediate risk of Trisomy 21. Universal screening has the potential for averting childhood morbidity at birth and by 5-years-old. Important variables influencing the ICER include the effectiveness of valacyclovir in preventing vertical transmission, prevalence of primary CMV infection, probability of symptomatic cCMV after periconception primary infection and cost of serology tests.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1234-1243"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584653","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":"The Influence of the Introduction of Fetal Anomaly Scans on Pregnancy Terminations in Cases of Upper Limb Anomalies: A Retrospective Cohort Study From 2000 to 2023.","authors":"Arda Arduç, Eline Huiberts, Margriet H M van Doesburg, Ingeborg H Linskens, Elisabeth van Leeuwen, Merel C Van Maarle, Eva Pajkrt","doi":"10.1002/pd.6882","DOIUrl":"https://doi.org/10.1002/pd.6882","url":null,"abstract":"<p><strong>Objective: </strong>To examine the association between the introduction of the fetal anomaly scans in the Netherlands and termination of pregnancy (TOP) in cases of prenatally detected upper limb anomalies.</p><p><strong>Methods: </strong>We conducted a retrospective study among prenatally detected upper limb anomalies between 2000 and 2023. Anomalies were categorized as reduction defects, syndactyly, or polydactyly, and classified as isolated or non-isolated. We analyzed TOP rates across three periods (2000-2006, 2007-August 2021, September 2021-2023), including an interrupted time series (ITS) analysis to assess the impact of introducing second- and first-trimester anomaly scans (STAS, FTAS).</p><p><strong>Results: </strong>We included 300 pregnancies, of which 133 (44.3%) were isolated. Overall TOP rates did not differ significantly between periods, except for isolated reduction defects, where a significant increase was observed (p = 0.032). TOP rates over time did not increase for syndactyly and polydactyly. Median gestational age at diagnosis decreased across the three periods: from 20.4 to 19.4 weeks and then to 14.9 weeks. Similarly, the timing of termination of pregnancy decreased from 20.5 to 16.8 weeks and then to 15.0 weeks.</p><p><strong>Conclusion: </strong>Earlier prenatal detection followed the introduction of STAS and FTAS. Despite this shift in timing, no consistent changes in termination rates were observed across the study periods. While overall TOP rates remained stable, a trend towards higher termination rates was observed for isolated reduction defects.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966111","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":"Assessment of the Fetal Sylvian Fissure in the Setting of Diffuse Cortical Abnormalities Detection: A Comparison of Published Methods.","authors":"Corinne Labadini, Andrea Dall'asta, Raphael Bartin, Carmela Putino, Pierre Mace, Tullio Ghi, Edwin Quarello","doi":"10.1002/pd.6876","DOIUrl":"https://doi.org/10.1002/pd.6876","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study is to compare the accuracy of the currently published techniques for Sylvian fissure (SF) evaluation on the axial plane in normal fetuses and in fetuses with confirmed diffuse malformation of cortical development (MCD).</p><p><strong>Methods: </strong>We performed a retrospective study in which the SF was assessed from fetuses between 22 and 33 weeks of gestation on a 2D transabdominal axial plane by means of subjective and objective methods derived from a literature search. The accuracy of the different techniques to predict the presence or the absence of MCD was compared.</p><p><strong>Results: </strong>100 fetuses were included at a median gestational age of 26 (22-33) weeks. Of these, 93 fetuses were normal. Subjective evaluation showed 100% (95% CI: 65-100) sensitivity and 100% (95% CI: 96-100) specificity for predicting the absence or presence of MCD. Conversely, when applying objective methods in the evaluation of the SF, the sensitivity ranged from 29% (95% CI: 8-64) to 57% (95% CI: 25-84) and the specificity from 23% (95% CI: 15-32) to 98% (95% CI: 92-100).</p><p><strong>Conclusions: </strong>The comparison of different methods for the expert assessment of the SF in the axial plane has shown that the subjective evaluation of the SF may be more accurate than other proposed methods in predicting the presence or absence of diffuse MCD. Further prospective research is needed to validate these results in daily practice.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966134","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":"Maternal Vascular Malperfusion and Anatomic Cord Abnormalities Are Prevalent in Pregnancies With Fetal Congenital Heart Disease.","authors":"Chrystalle Katte Carreon, Christina Ronai, Julia K Hoffmann, Wayne Tworetzky, Sarah U Morton, Louise E Wilkins-Haug","doi":"10.1002/pd.6650","DOIUrl":"10.1002/pd.6650","url":null,"abstract":"<p><strong>Objective: </strong>Impairments in the maternal-fetal environment are associated with adverse postnatal outcomes among infants with congenital heart disease. Therefore, we sought to investigate placental anomalies as they related to various forms of fetal congenital heart disease (FCHD).</p><p><strong>Methods: </strong>We reviewed the placental pathology in singleton pregnancies with and without FCHD. FCHD was divided into separate categories (transposition physiology, obstructive left, obstructive right, biventricular without obstruction, and others). Exclusion criteria included other prenatally known structural malformations and/or aneuploidy. The significance threshold was set at p < 0.05 or False Discovery rate q < 0.05 when multiple tests were performed.</p><p><strong>Results: </strong>The cohort included 215 FCHD and 122 non-FCHD placentas. FCHD placentas showed increased rates of maternal vascular malperfusion (24% vs. 5%, q < 0.001) and cord anomalies (27% vs. 1%, q < 0.001). Placentas with fetal TGA demonstrated a lower rate of hypoplasia when compared with other FCHD types (1/39 vs. 51/176, Fisher's exact p = 0.015).</p><p><strong>Conclusion: </strong>Placental maternal vascular malperfusion is increased in FCHD. The prevalence of vascular malperfusion did not differ by FCHD type, indicating that CHD type does not predict the likelihood of placental vascular dysfunction. Further investigation of the placental-fetal heart axis in FCHD is warranted given the importance of placental health.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1325-1333"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111129","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":"Diagnostic Yield of Exome Sequencing for Pregnancies With and Without Fetal Anomalies and for Stillbirth.","authors":"Roni Zemet, Christian M Parobek, April D Adams, Mohamad Ali Maktabi, Lena Shay, Linyan Meng, Pengfei Liu, Hongzheng Dai, Fan Xia, Christine Eng, Ignatia B Van den Veyver, Liesbeth Vossaert","doi":"10.1002/pd.6817","DOIUrl":"10.1002/pd.6817","url":null,"abstract":"<p><strong>Objective: </strong>Exome sequencing (ES) benefits the genetic work-up for fetuses with structural anomalies, but data on its utility for fetuses without anomalies and stillbirths is more limited. We report our experience with prenatal ES for all three indications.</p><p><strong>Method: </strong>We retrospectively reviewed results from 344 trio-ES performed for fetuses with structural anomalies (N = 262), stillbirths (N = 39), and fetuses without anomalies (N = 43), many of which had a relevant family history. We classified pathogenic variants (P), likely pathogenic variants (LP), or variants of uncertain significance (VUS) favoring pathogenicity in a gene consistent with the fetal phenotype as diagnostic results. We used Fisher's exact test for statistical analysis.</p><p><strong>Results: </strong>Trio-ES provided a diagnosis for 93/262 (35.5%) fetuses with structural anomalies, with comparable yields for multiple and single anomalies (p = 0.81). A molecular diagnosis was made for 10/39 stillbirths (25.6%), of which all but one had structural anomalies, and 66.6% had multiple anomalies. In the absence of structural anomalies, one of 43 fetuses (2.3%) was found to have compound heterozygous pathogenic variants in ORC6 associated with Meier-Gorlin syndrome.</p><p><strong>Conclusion: </strong>Prenatal trio-ES yields molecular diagnoses across a spectrum of indications. Larger studies are needed to further define the added benefits and challenges of diagnostic ES for fetuses without anomalies.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1313-1324"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151486","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}