Prenatal Diagnosis最新文献

{"title":"'When Lightning Strikes Twice'-Preimplantation Genetic Testing for Two Indications in One Biopsy.","authors":"Einav Kremer, Hagit Daum, Amy Solnica, Tamar Krisher, Assaf Ben Meir, Efrat Esh-Broder, Mali Ketzinel Gilad, Talya Daniel Mordechai, Tal Imbar","doi":"10.1002/pd.6779","DOIUrl":"https://doi.org/10.1002/pd.6779","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to investigate whether the clinical pregnancy and live birth rates in women undergoing preimplantation genetic testing for two indications (PGT2) differ from PGT for one autosomal dominant indication (PGT1).</p><p><strong>Method: </strong>This retrospective cohort study summarizes data from 44 PGT patients treated between 2015 and 2023. Data were divided into PGT2 (n = 22 patients, 113 treatment cycles) and PGT1 (n = 22 patients, 108 treatment cycles) groups. Statistical analysis included descriptive statistics, independent t-tests, Mann-Whitney U tests, mixed models, and multivariable mixed logistic regressions.</p><p><strong>Results: </strong>The groups did not differ in clinical pregnancy and live birth rates. PGT2 patients had more fresh embryos per cycle than the PGT1 group (4.84 vs. 3.18 respectively; p = 0.067) and a significantly lower number of frozen embryos after biopsy (0.29 vs. 0.60 respectively; p = 0.037). No difference was found regarding the mean suitable embryos for biopsy. The PGT2 group had fewer embryos to transfer per cycle (1.30 vs.1.89; p = 0.007), yet there was no difference regarding the number of transferred embryos per cycle.</p><p><strong>Conclusion: </strong>Testing for two genetic indications in one biopsy is feasible yet yields a lower proportion of embryos genetically suitable for transfer but with a similar live birth rate.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649999","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":"Digital PCR Assay Utilizing In-Droplet Methylation-Sensitive Digestion for Estimation of Fetal cfDNA From Plasma.","authors":"Richard Dannebaum, Olga Mikhaylichenko, David Siegel, Chenyu Li, Eric Hall, Severine Margeridon, Monica Herrera, Kristin Loomis, Thea Riel, Madhumita Ramesh, Maria Gencoglu, Nathan Hendel, Anthony Henriquez, Nyari Dzvova, Raymond-John Abayan, Xinhua Lin, Martin Chavez, Nazeeh Hanna","doi":"10.1002/pd.6774","DOIUrl":"https://doi.org/10.1002/pd.6774","url":null,"abstract":"<p><strong>Objective: </strong>Recent guidelines suggest that non-invasive prenatal screening (NIPS) should be offered to all patients with singleton and twin pregnancies. Accurate determination of fetal fraction in cell-free DNA (cfDNA) is vital for reliable NIPS outcomes. We propose a methylation-based approach using droplet digital PCR (ddPCR) and methylation-sensitive restriction enzyme (MSRE) digestion for fetal fraction quantification as an affordable and fast solution.</p><p><strong>Method: </strong>Following biomarker discovery using early pregnancy placental genomic DNA (gDNA) and cfDNA from non-pregnant female individuals, we designed assays targeting MSRE-compatible regions based on contrasting methylation patterns between maternal and fetal cfDNA. We established a proof-of-concept ddPCR workflow on the Bio-Rad Droplet Digital PCR QX600 instrument.</p><p><strong>Results: </strong>Testing the fetal fraction assay multiplex on 137 prospective clinical samples demonstrated high concordance with NGS results for both female and male pregnancies as well as with chromosome Y-based calculations for samples with a male fetus. Reproducibility analysis indicated lower variability compared to previously reported NGS performance.</p><p><strong>Conclusion: </strong>This study showcases the potential of this novel, 6-color, high-multiplex methylation ddPCR panel for accurate measurement of fetal fraction in cfDNA samples. It presents opportunities to integrate such methodology as a standalone measurement to assess the quality of samples undergoing NIPS.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639797","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":"Improving the Performance of Prenatal Cell-Free DNA Screening Through Size-Selective Fetal DNA Enrichment in a Cohort of 71,986 General and High-Risk Pregnancies.","authors":"Liang Hu, Lijuan Wen, Yanan Liu, Xiaohang Chen, Jiatong Zhong, Weiqiang Liu, Fengxiang Wei","doi":"10.1002/pd.6775","DOIUrl":"https://doi.org/10.1002/pd.6775","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the performance of prenatal cell-free DNA (cfDNA) screening with and without the cell-free fetal DNA enrichment method in general-risk and high-risk pregnancies.</p><p><strong>Methods: </strong>We performed a size-selective cell-free fetal DNA enrichment in 71,986 pregnancies. The cfDNA screening and follow-up results were collected for trisomies 21, 18, 13, fetal sex chromosome abnormalities (SCAs), and copy number variants (CNVs). The fetal fraction of cfDNA, positive rates, and positive predictive values (PPV) were compared between the general-risk and high-risk pregnancies with and without enrichment.</p><p><strong>Results: </strong>With the cell-free fetal DNA enrichment, the fetal fraction of cfDNA increased to 18.87 ± 5.94. The overall PPVs for common trisomies increased to 88.46% and 91.11% in the general- and high-risk populations, respectively. For CNVs, the PPVs with enrichment increased to 53.52% and 66.67% in the general risk and high-risk populations, respectively. However, for SCAs, the PPV was not improved by cell-free fetal DNA enrichment. The failure rates in the general-risk and high-risk groups decreased to 0.01% and 0.08%.</p><p><strong>Conclusions: </strong>Cell-free fetal DNA enrichment significantly improves the PPVs of common trisomies and CNVs in general and high-risk populations. It has the potential for the clinical application effect of cell-free DNA screening.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634314","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 Fall Out of the 2017 European Medical Device Regulation for Tracheal Occlusion.","authors":"Francesca Russo, Alexandra Benachi, Frank Meijer, Fanny Cauvet, Hélène Berrué-Gaillard, Beverley Power, Jan Deprest","doi":"10.1002/pd.6763","DOIUrl":"https://doi.org/10.1002/pd.6763","url":null,"abstract":"<p><strong>Objective: </strong>The use of the Balt Goldbal-balloon and Baltacci-catheter in Fetoscopic Endoluminal Tracheal Occlusion is affected by the 2017-European Medical Device Regulation, which necessitates recertification even for devices long considered safe. This regulation has led the manufacturer to stop distributing these devices in Europe. We alert fetal surgery centers to these challenges and regulators to the broader impact on the availability of fetal therapy devices in Europe.</p><p><strong>Methods: </strong>We surveyed 50 fetal surgery centers worldwide and communicated directly with the manufacturer. Additionally, we provide updates on a new device under evaluation.</p><p><strong>Results: </strong>The response rate among 39 balloon users was 95% (n = 37). Currently, all balloons in Europe are expired. Supply issues exist in Australasia and South-America, with some distributors reporting discontinuation despite the manufacturer's communications on its sustained availability. Some centers manage shortages by importing from other countries. Balt has agreed to supply devices to European centers that obtain derogation by the national competent authorities, for which we cannot provide a generic procedure. An alternative device is unlikely to be marketed before 2026.</p><p><strong>Conclusion: </strong>This scenario highlights the unintended consequences of stringent medical device regulations, leading to their unavailability for beneficial procedures or complicated administrative processes, even as these devices remain available outside the EU.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634318","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":"Fetal Urinoma Secondary to Posterior Urethral Valve and Its Association to Postnatal Renal Function: A Multicenter Retrospective Study.","authors":"Flore-Anne Martin, Matthieu Peycelon, Nicolas Vinit, Thibault Planchamp, Olivier Abbo, Maela Le Lous, Gwenaelle Le Bouar, Yves Ville, Annabelle Paye-Jaouen, Thomas Blanc, Alexis P Arnaud","doi":"10.1002/pd.6773","DOIUrl":"https://doi.org/10.1002/pd.6773","url":null,"abstract":"<p><strong>Aim: </strong>The role of prenatal urinoma in lower urinary tract obstruction (LUTO) such as posterior urethral valves (PUV) is debated. We aimed to describe the risk factors associated with fetal urinoma and the association between fetal urinoma and postnatal renal function before 2 years of age.</p><p><strong>Methods: </strong>This retrospective multicenter case-control study from 2000 to 2018 included pregnant patients with suspected LUTO in their male fetus on prenatal ultrasound and postnatal confirmation of PUV. The exposure criterion was prenatal urinoma. The main composit outcome (MCO) was chronic kidney disease stage 3 or higher (CKD3+) before 2 years or death. Descriptive analyses of patient data and crude and multivariate logistic regression analyses were performed in an intent-to-treat fashion, thus including lost-to-follow-up patients. Ethical approval # 20.144.</p><p><strong>Results: </strong>We included 299 patients, of whom 39 (13%) had prenatal urinoma. Thirty-eight patients had a termination of pregnancy (12.7%). Sixty-four (24.5%) patients'children were MCO positive. Twenty-one children were lost-to-follow-up, including one prenatal urinoma. Thirty-nine (60.9%) of the remaining children had CKD3+ before the age of two, of whom 6 had a prenatal urinoma (9.4%). Among the 197 children negative to the MCO, 24 had a prenatal urinoma (12.2%, p = 0.42). Four died neonatally. In livebirth patients, prenatal urinoma was associated with obstetrical complications (p = 0.02), prenatal bloodcord sample for fetal beta2-microglobulin (p = 0.01) and uro-amniotic shunt (p = 0.01). Patients with prenatal urinoma more often presented with oligohydramnios (p = 0.01) and dilated posterior urethra (p = 0.01) and were less likely to have urinary tract infections (p = 0.02), although their DMSA scan was more often altered (p = 0.001). Prenatal urinoma was not significantly associated with CKD3+ before 2 years (OR = 0.56, CI98% = 0.20-1.39, p = 0.23).</p><p><strong>Conclusion: </strong>Renal function in infants with PUV was not worsened by the presence of a prenatal urinoma. Thus, there should not be any more pejorative message conveyed to concerned couples apart from other already known prenatal poor prognosis risk factors.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625673","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":"Challenges in Identifying the Cause of Fetal Sinus Bradycardia: Coexistence of Maternal Anti-SSA Antibodies and Holt-Oram Syndrome Due to a Novel TBX5 Variant.","authors":"Xiaohui Dai, Shuran Shao, Fuping Yue, Jiao Chen, Hong Luo, Ju Gao, Yu Wang, Chuan Wang","doi":"10.1002/pd.6770","DOIUrl":"https://doi.org/10.1002/pd.6770","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586714","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":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perinatal Outcomes in Appropriately Grown Monochorionic Diamniotic Twins With Intermittent Absent and Reversed End-Diastolic Umbilical Artery Flow Compared to Selective Fetal Growth Restriction Type III.","authors":"Elizabeth Schlant, Abby Birk, Ahmet Baschat, Michelle Kush, Lindsey Goodman, Sarah Olson, Kristin Voegtline, Jena Miller, Mara Rosner","doi":"10.1002/pd.6717","DOIUrl":"10.1002/pd.6717","url":null,"abstract":"<p><strong>Objectives: </strong>Umbilical artery Doppler intermittent absent and reversed end-diastolic flow (iAREDF) is associated with increased perinatal morbidity and mortality in monochorionic twins with selective fetal growth restriction. The clinical significance of umbilical artery iAREDF in appropriately grown monochorionic twins is not well described.</p><p><strong>Methods: </strong>This is a single-institution retrospective cohort study describing characteristics and outcomes of monochorionic diamniotic twins with appropriate for gestational age growth and umbilical artery iAREDF in comparison to monochorionic diamniotic twins with selective fetal growth restriction and iAREDF, or sFGR type III. The cohorts were compared for antenatal resolution of iAREDF, estimated gestational age at delivery, fetal and maternal complications, delivery characteristics, and survival outcomes.</p><p><strong>Results: </strong>Ten appropriately grown monochorionic diamniotic twin pairs with umbilical artery iAREDF and 23 with sFGR Type III delivered at a mean gestational age of 30.4 (± 5) weeks and 30.7 (± 4) weeks, respectively (p = 0.93). No significant differences were observed in the Doppler course (deterioration or improvement) prior to delivery, fetal or maternal complications, delivery characteristics (with the exception of the persistence of the growth differences), or survival outcomes between groups.</p><p><strong>Conclusions: </strong>Monochorionic diamniotic twins with intermittent absent and reversed end-diastolic umbilical artery velocity may be at increased risk for adverse perinatal outcomes even if criteria for selective fetal growth restriction are not met.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"387-395"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838773","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":"Navigating the Challenges of Exome Sequencing in Structurally Normal Fetuses.","authors":"Sylvie Langlois, Lyn S Chitty","doi":"10.1002/pd.6766","DOIUrl":"https://doi.org/10.1002/pd.6766","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":"45 3","pages":"273-275"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597661","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":"Has the Era of Individualized Intrauterine Treatment for Congenital Adrenal Hyperplasia Arrived?","authors":"Xinyu Fu, Yanjie Xia, Shaojun Li, Zhenhua Zhao, Lingrong Kong, Jingqi Zhu, Huanyun Li, Shitong Wu, Di Wu, Xiangdong Kong","doi":"10.1002/pd.6747","DOIUrl":"10.1002/pd.6747","url":null,"abstract":"<p><strong>Background: </strong>Congenital adrenal hyperplasia (CAH) is a common metabolic genetic disease. Early diagnosis and intervention are crucial to improve the prognosis. Noninvasive prenatal diagnosis (NIPD) is an early, safe, and accurate method. This study aimed to evaluate the NIPD of CAH while guiding individualized intrauterine treatment.</p><p><strong>Methods: </strong>Twenty families with a 25% risk of having a baby with 21-hydroxylase deficiency (21-OHD) were included. Haplotypes were constructed based on targeted sequencing and family linkage analysis. Relative haplotype dosage (RHDO) combined with Bayes factor was used to infer fetal genotypes. Invasive prenatal diagnosis was performed to verify the reliability of NIPD. For affected-female fetuses, intrauterine treatment was applied until delivery.</p><p><strong>Results: </strong>In 20 families, NIPD successfully identified one female-affected fetus, four male-affected fetuses, nine heterozygotes, and five normal fetuses. The first-pass success rate of NIPD was 90% (18/20), the reporting rate was 95% (19/20), and the accuracy was 100% (19/19). Individualized intrauterine treatment avoided 88.9% (8/9) of unnecessary treatment of unaffected female fetuses. Moreover, no significant virilization was observed in the newborn of CAH16, which underwent intrauterine treatment.</p><p><strong>Conclusion: </strong>NIPD has far-reaching implications for the early treatment and clinical management of pregnancy in families with 21-OHD.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"423-432"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075297","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}