Prenatal Diagnosis最新文献

{"title":"Fetal Intracranial Hemorrhage: What to Tell Expecting Parents?","authors":"Shiri Shinar, Yada Kunpalin, Elka Miller","doi":"10.1002/pd.70253","DOIUrl":"https://doi.org/10.1002/pd.70253","url":null,"abstract":"<p><p>To review the classification, epidemiology, etiology, prenatal diagnostic approach, and neurodevelopmental outcomes of fetal intracranial hemorrhage (ICH), and to provide clinicians with a practical, fetal-specific framework for investigating and counseling families facing this diagnosis. Narrative review of the current evidence on fetal ICH, encompassing intraventricular hemorrhage (IVH) and periventricular hemorrhagic infarction (PVHI), cerebellar hemorrhage, and extra-axial bleeding, with a primary focus on IVH as the most common presentation. The true prenatal incidence of fetal ICH is uncertain, with estimates of 0.5-1 per 10,000 pregnancies likely underestimating the true burden. Etiologies are diverse, including fetal-neonatal alloimmune thrombocytopenia (FNAIT), monogenic vasculopathies (notably COL4A1/COL4A2), congenital infection, fetal anemia, coagulopathy, and twin-related complications; however, a definitive cause is identified in fewer than half of cases even after complete workup, with a genetic etiology found in roughly 30% of fully investigated cases. Detailed neurosonography remains the primary diagnostic tool, with fetal MRI serving as an important adjunct for characterizing hemorrhage extent, associated parenchymal injury, and posterior fossa involvement. Outcomes vary substantially by hemorrhage grade, location, and laterality: low-grade IVH generally carries a favorable prognosis, while PVHI-for which the Bassan territorial classification aids prognostication-carries substantially higher rates of cerebral palsy, ventriculoperitoneal shunting, and cognitive impairment, particularly when extensive and bilateral. Existing prognostic data derive largely from small, heterogeneous neonatal cohorts using a grading system not designed for the fetal context, limiting the precision of individualized counseling. Fetal ICH is rare, etiologically heterogeneous, and variable in severity, and current evidence does not support precise individualized outcome prediction. A thorough, systematic evaluation and an interdisciplinary team approach are essential, with transparent communication about the inherent uncertainties forming the foundation of parental counseling.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008794","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":"Novel and High-Throughput Method of Isolating Single Fetal Cells Using FACS for NIPT.","authors":"Ripudaman Singh, Bolette Hestbek Nicolaisen, Mathias Kølvraa, Inga Baasch Christensen, Mads Tang Dalsgaard, Lars Henning Pedersen, Niels Uldbjerg, Ida Vogel, Lotte Hatt, Katarina Ravn","doi":"10.1002/pd.70219","DOIUrl":"10.1002/pd.70219","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate fluorescence activated cell sorting (FACS) as a method of single-cell isolation of rare circulating fetal cells from maternal blood for use in cell-based non-invasive prenatal testing (cbNIPT).</p><p><strong>Method: </strong>Blood samples (30 mL) were collected from 75 'low-risk' pregnant women (gestational age 10-15 weeks). Fetal cells were enriched and stained using magnetic activated cell sorting. Following enrichment, single fetal cells were sorted in individual PCR tubes by FACS. After cell lysis, verification of fetal cell origin was performed using short tandem repeat (STR) analysis with the GlobalFiler PCR Amplification kit.</p><p><strong>Results: </strong>An average of 13.7 cells were sorted using FACS. STR analysis identified 8.2 fetal cells on average, representing 60.2% of the sorted cells. The four-step single-cell isolation procedure facilitated an overall enrichment of approximately 16-million-fold. One sample did not render any fetal cell, corresponding to 1.3% of the samples.</p><p><strong>Conclusion: </strong>FACS, which is typically used for segregation of large populations of cells, can be used for single-cell isolation of rare fetal cells in an automated setup. This not only helps in making cell isolation faster and high throughput but also provides fetal cells for a more comprehensive genetic analysis of the fetus.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1536-1542"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405637","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":"Is There Potential Clinical Utility in Reporting Variants of Uncertain Significance From Prenatal Sequencing?","authors":"A Gibbs, R Braham, V Ramachandran, R Roberts, C Willison, T Ashraf, J Cobben, A Gardham, M Holder-Espinasse, T Homfray, S G Mehta, D Tapon, P Vasudevan, N J Chandler","doi":"10.1002/pd.70192","DOIUrl":"10.1002/pd.70192","url":null,"abstract":"<p><strong>Objective: </strong>Prenatal sequencing of fetuses with abnormalities detected on imaging is expanding globally. Debate continues over whether variants of uncertain significance (VUS) should be reported prenatally, with some recent national position statements opposing this. In England, VUS that fit the fetal phenotype and require little further evidence for upgrade are discussed at multidisciplinary team (MDT) meetings to determine whether to report. We review the VUS reported by one English laboratory that provides prenatal sequencing to half of England.</p><p><strong>Method: </strong>The laboratory's database was searched from 01/10/2020 to 30/04/2025 to ascertain all cases where a VUS was reported. Pregnancy outcomes were obtained from local clinical teams to determine whether the VUS status had been resolved.</p><p><strong>Results: </strong>VUS were reported in 41/881 fetuses sequenced. Follow-up data were available for 38/41 cases, of which 23 were subsequently upgraded to likely pathogenic and 1 downgraded to likely benign. The most common reason for upgrade was new information from post-mortem or postnatal review (17/23).</p><p><strong>Conclusion: </strong>There is clinical utility in reporting VUS from prenatal sequencing following MDT discussion. Although reporting VUS leaves parents with uncertainty, follow up (including post-mortem when applicable) resolves this in over 50% of cases (79% of cases re-examined pre- or postnatally).</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1557-1564"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148278440","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":"Diagnostic Testing After Positive Cell-Free DNA Screening for Sex Chromosome Aneuploidies: Clinical and Socioeconomic Determinants.","authors":"Blair K Stevens, Sarah Araji, Mohamad Ali Maktabi, Randy Liu, Lauren Westerfield, Michael Wassef, Dejian Lai, Ignatia B Van den Veyver, Meera Krishnan, Charlotte Lawrence, Siddharth K Prakash","doi":"10.1002/pd.70229","DOIUrl":"10.1002/pd.70229","url":null,"abstract":"<p><strong>Objective: </strong>To assess socioeconomic and medical factors associated with prenatal confirmatory diagnostic testing after positive prenatal cell-free (cfDNA) screening for sex chromosome aneuploidies (SCA) in a diverse contemporary patient cohort.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of patients who had abnormal prenatal cfDNA screening results indicative of SCA and were seen for genetic counseling between 2014 and 2024 at two tertiary academic medical centers. We used logistic regression analysis to evaluate the association of demographic and clinical factors with confirmatory testing.</p><p><strong>Results: </strong>Of the 692 patients with abnormal cfDNA results, 26% (n = 180) underwent diagnostic testing. These patients were older, resided in more affluent areas, presented earlier for genetic counseling, were more likely to have commercial insurance, and were less likely to prefer Spanish or use an interpreter. Compared to Non-Hispanic (NH) Whites, diagnostic testing rates were higher for NH Asians but were lower for NH Blacks and Hispanics or when results indicated XYY or XXX. In logistic modeling, lower deprivation scores and commercial insurance were independently associated with higher testing rates.</p><p><strong>Conclusion: </strong>Only 1 in 4 patients pursued prenatal diagnostic testing following positive cfDNA screening for SCAs. Race, ethnicity, socioeconomic status and preferred language were the primary determinants of testing.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1529-1535"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654040","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":"A Simplified Workflow for the Prediction of Putative Viral Reads Using NIPT Data.","authors":"Shabnam Shahidi, Atousa Dabiri Oskoei, Akbar Mohammadzadeh, Hessam Mirshahabi, Kamyar Mansori, Hossein Dinmohammadi, Hassan Rokni-Zadeh","doi":"10.1002/pd.70233","DOIUrl":"10.1002/pd.70233","url":null,"abstract":"<p><strong>Objective: </strong>Non-invasive prenatal testing (NIPT) identifies fetal chromosomal abnormalities by sequencing cell-free fetal DNA (cffDNA). Recent studies suggest the prediction of viral sequences from NIPT data, but current methods lack cost-effectiveness for routine use. This study develops a straightforward workflow to investigate potential viral signatures in pregnant women using NIPT data from 888 Iranian participants.</p><p><strong>Method: </strong>Two bioinformatic workflows were compared for predicting viral reads: the traditional method involved mapping reads to the human genome, followed by mapping unmapped reads to viral references, and a direct mapping approach to viral genomes, as proposed in this research.</p><p><strong>Results: </strong>While maintaining reproducibility comparable to the conventional method, the proposed workflow minimizes computational complexity and time usage for data processing. Ultimately, this analysis suggested viral DNA in 24.2% of samples, encompassing 29 distinct species, implying the diversity of the maternal virome.</p><p><strong>Conclusion: </strong>This study presents a computationally efficient workflow for the in silico prediction of viral-like sequences from routine NIPT data. Further experimental validation is essential to verify the presence, viability, or clinical relevance of these sequences.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1549-1556"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679842","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":"Comparison of Medium-Coverage Whole-Genome Sequencing and Chromosomal Microarray in Prenatal Testing of Absence of Heterozygosity.","authors":"Mengdie Zhang, Juan Li, Chunying Ren, Yaming Liu, Wuke Bian, Xiao Han, Mengru Wang, Xiaotian Chen, Yukun Hu, Meilin Kan, Ling Liu","doi":"10.1002/pd.70218","DOIUrl":"10.1002/pd.70218","url":null,"abstract":"<p><strong>Objective: </strong>Absence of heterozygosity (AOH) is a clinically significant genomic feature often associated with uniparental disomy and parental consanguinity in the prenatal settings. Chromosomal microarray analysis (CMA) is commonly used for AOH detection, while sequencing-based approaches may provide complementary genomic information within a single assay. This study evaluated the performance of medium-coverage whole-genome sequencing (CNV-plus) for the detection of prenatal AOH.</p><p><strong>Methods: </strong>We analyzed 45 prenatal samples (35-CMA-positive, 10-CMA-negative). Concordance between CNV-plus and CMA was assessed at regional, genome-wide, and sample levels, with particular emphasis on the effect of AOH segment size.</p><p><strong>Results: </strong>CNV-plus detected 56 AOH regions compared with 65 by CMA, yielding 68 matched segments. Segment-level sensitivity was 86.8%, showing clear size dependence: 53.3% for 5-10 Mb regions and 96.2% for regions > 10 Mb. Genome-wide overlap was high (global Jaccard index = 0.871), although boundary resolution differed between methods. At the sample level, CNV-plus achieved 97.1% sensitivity and 100% specificity, with no significant difference from CMA.</p><p><strong>Conclusions: </strong>CNV-plus demonstrates good concordance with CMA for detecting larger AOH regions in prenatal samples and may serve as a complementary approach when considering its size-dependent performance.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1565-1581"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679834","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":"Artificial Intelligence as an Add-On Instrument in Fetal Ultrasound; Sonographers' and Obstetricians' Expectations.","authors":"Renée M Smit, Chiara C M M Lap, Rima Arnaout, Anita J Moon-Grady, Monique C Haak","doi":"10.1002/pd.70133","DOIUrl":"10.1002/pd.70133","url":null,"abstract":"<p><strong>Objective: </strong>Artificial intelligence applications (AIA) in fetal ultrasound are rapidly evolving, yet their integration into routine clinical practice remains limited. This study explores the attitudes, expectations and concerns of obstetric sonographers and gynecologists regarding AIA as a diagnostic aid during fetal anomaly scans.</p><p><strong>Method: </strong>An online survey was distributed to sonographers, midwives, gynecologists and fetal medicine consultants performing screening and diagnostic fetal ultrasounds in the Netherlands. The survey included demographics, current use of artificial intelligence (AI), and 22 attitudinal statements rated on acceptance, efficiency, safety, and quality. Respondents were grouped by age, AI experience, and scan type.</p><p><strong>Results: </strong>Among 151 respondents, 47% were sonographers performing standard anomaly screening and 49% were performing diagnostic anomaly scans at tertiary-level centers. AI was already used by 62%, primarily for automated biometry. Overall, 87% supported AIA use, yet 86% emphasized retaining final clinical authority. Concerns about data security (10%) and software manipulation (12%) were minimal. While 73% of the surveyed respondents believed AIA can improve scan completeness, only 39% expect workload reduction and 70% expect improved anomaly detection.</p><p><strong>Conclusion: </strong>Obstetric sonographers generally support AIA integration, anticipating a positive impact on screening outcomes. However, human decision-making remains essential. These insights may guide future implementation strategies and offer momentum to influence referral practices.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1591-1597"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582012","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":"Prenatal Phenotypic Features of Five Fetal Cases With RNU4ATAC-Associated Microcephalic Osteodysplastic Primordial Dwarfism Type I.","authors":"Alexandra Liebmann, Tanja Richter, Nevena Krstić, Markus Hoopmann, Karl Oliver Kagan, Lena-Sophie Menig-Benzig, Simone Olivieri, Olaf Riess, Andreas Dufke","doi":"10.1002/pd.70240","DOIUrl":"10.1002/pd.70240","url":null,"abstract":"<p><strong>Objective: </strong>To present the prenatal sonographic features, genomic findings, and pregnancy outcomes of fetuses with biallelic pathogenic RNU4ATAC variants linked to microcephalic osteodysplastic primordial dwarfism type I (MOPD1).</p><p><strong>Methods: </strong>This retrospective case series includes five prenatal cases with MOPD1. Diagnoses were established by prenatal ultrasound and genetic testing. Genome sequencing (GS) or targeted exome sequencing (ES) detected the variants either prenatally or after termination of pregnancy (TOP). Clinical data including parental demographics, ultrasound findings, and pregnancy outcomes were collected.</p><p><strong>Results: </strong>All fetuses presented with consistent anomalies on ultrasound including intrauterine growth restriction (IUGR), microcephaly, agenesis of the corpus callosum (ACC), intracranial cysts, lissencephaly, and micrognathia. IUGR was the earliest anomaly detected in all five cases. Prenatal ultrasound findings suggestive of skeletal dysplasia were identified in one case. All cases carried biallelic pathogenic RNU4ATAC variants associated with MOPD1. TOP was chosen in four cases. One fetus was delivered at 39 + 1 weeks with genetic diagnosis confirmed at 27 weeks.</p><p><strong>Conclusion: </strong>IUGR, microcephaly and ACC can be detected in fetuses with MOPD1 at around 18 weeks of gestation. Interestingly, skeletal dysplasia was not a consistent prenatal finding. Variants in the non-coding RNU4ATAC gene need to be detected by GS or targeted approaches beyond standard ES.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1648-1654"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761640","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":"First-Trimester Bilateral Choanal Atresia as a Marker of a De Novo Pathogenic KMT2D Variant Associated With BCAHH Syndrome.","authors":"Patrik Šimják, Jan Král, Dagmar Rašková, Monika Koudová, David Stejskal","doi":"10.1002/pd.70227","DOIUrl":"10.1002/pd.70227","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1667-1671"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148593166","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":"Enhancing Prenatal Genetic Evaluation Through the Combination of Single-Gene Non-Invasive Prenatal Screening and Prenatal Imaging.","authors":"Sarah Araji, Jennifer L Cohen","doi":"10.1002/pd.70204","DOIUrl":"10.1002/pd.70204","url":null,"abstract":"<p><p>Cell free DNA (cfDNA) screening for common aneuploidies is now widely integrated into prenatal care, and recent advances in next-generation sequencing, enhanced by unique molecular indexing methodology, have enabled cfDNA for selected single-gene disorders (cfDNA-SGD). Commercially available cfDNA-SGD panels target predominantly either de novo autosomal dominant or X-linked conditions that have recognizable prenatal or neonatal phenotypes. However, it remains a screening modality that relies on placental cell-free DNA, and encounters limitations. In this review, we summarize a currently available cfDNA-SGD panel that screens for 25 autosomal or X-linked dominant conditions corresponding to 30 unique genes, with several genes contributing to multiple conditions on the panel. We highlight the potentially associated prenatal and postnatal phenotypes and the imaging modalities that may help refine a prenatal genetic evaluation. We also discuss how ultrasound, fetal echocardiography, and fetal MRI across all trimesters can refine the prenatal differential diagnosis and help contextualize cfDNA-SGD results, while emphasizing that imaging findings remain the primary guide for management and that confirmatory diagnostic testing is required before clinical decisions and action.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1508-1519"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295904","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}