Prenatal Diagnosis最新文献

{"title":"Maternal cell contamination in postnatal umbilical cord blood samples implies a low risk for genetic misdiagnoses.","authors":"Sanne P Smeekens, Maike Leferink, Helger G Yntema, Erik-Jan Kamsteeg","doi":"10.1002/pd.6595","DOIUrl":"10.1002/pd.6595","url":null,"abstract":"<p><strong>Objective: </strong>Maternal cell contamination (MCC) poses a risk for misdiagnosis in prenatal genetic testing, and is examined in accredited diagnostic laboratories However, the awareness of possible MCC in perinatal/postnatal genetic testing, mainly of umbilical cord blood (CB), is lower.</p><p><strong>Method: </strong>We investigated the rate of MCC in DNA from both umbilical CB samples and umbilical cord samples that were sent to our diagnostic laboratory for diagnostic testing between 1995 and 2021 (n = 236).</p><p><strong>Results: </strong>MCC was detected in 4% of umbilical CB samples, and in one umbilical cord sample. Particularly tests enriching for a specific variant are very sensitive for low amounts of MCC, as we emphasize here with a false positive diagnosis of myotonic dystrophy type 1 in a newborn.</p><p><strong>Conclusions: </strong>Overall, with appropriate collection and use, umbilical CB and umbilical cord samples are suitable for genetic testing based on the low rates of MCC and misdiagnosis. These findings do however underline the importance of routine MCC testing in umbilical CB samples and umbilical cord samples for both requesting clinicians and diagnostic genetic laboratories.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1304-1309"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088374","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 Reliability of Ultrasound Markers in Identifying Fetuses With a Life-Limiting Skeletal Dysplasia.","authors":"Haley M Crane, Erica Schindewolf, Natalie Burrill, Suzanne Debari, Nahla Khalek, Christina Paidas Teefey, Shelly Soni, Beverly Coleman, Julie S Moldenhauer, Juliana Gebb","doi":"10.1002/pd.6638","DOIUrl":"10.1002/pd.6638","url":null,"abstract":"<p><strong>Objective: </strong>To determine the diagnostic performance of ultrasound markers associated with life-limiting fetal skeletal dysplasia in a fortified cohort.</p><p><strong>Methods: </strong>Retrospective review from 2013 to 2023 of pregnancies with suspected fetal skeletal dysplasia. Ultrasound evaluation included measurements predictive of a life-limiting dysplasia: thoracic circumference/abdominal circumference (TC/AC) < 0.6, femur length/abdominal circumference (FL/AC) < 0.16, and thoracic circumference (TC) < 2.5th percentile. Demographics, ultrasound findings, genetic testing, and fetal/neonatal outcome were reviewed.</p><p><strong>Results: </strong>Of 96 fetuses with complete outcome data, 47 (49%) had a non-life-limiting dysplasia and 49 (51%) had a life-limiting dysplasia. 22 (23%) had no life-limiting markers, 42 (44%) had one, 27 (28%) had two, and 5 (5%) had three. FL/AC < 0.16 and TC < 2.5th percentile were associated with life-limiting dysplasia (p < 0.001; p < 0.001), while TC/AC < 0.6 was rare and did not reach statistical significance (p = 0.056). The positive predictive value (PPV) for predicting life-limiting dysplasia increased from 50% to 78% to 100% with one, two, or three markers. The PPV of the two life-limiting markers was significantly higher in those diagnosed at < versus ≥ 28 weeks (90% vs. 43%, p = 0.02) but the analysis was limited by small numbers in the ≥ 28 weeks cohort. The negative predictive value of no life-limiting markers was 91%.</p><p><strong>Conclusions: </strong>In our cohort, the presence of two life-limiting ultrasound markers prior to 28 weeks was highly suggestive of a life-limiting dysplasia, whereas the absence of life-limiting markers was strongly associated with a non-life-limiting dysplasia throughout gestation. Nonetheless, individual markers had a poor predictive value of lethality, and a life-limiting diagnosis ≥ 28 weeks is challenging based on ultrasound markers alone. This highlights the importance of integrating thorough sonography, genetic testing, and balanced parental counseling.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1318-1326"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793093","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":"Exome sequencing in fetuses with congenital diaphragmatic hernia in a nationwide cohort.","authors":"Katinka Weller, Dineke Westra, Nina C J Peters, Martina Wilke, Diane Van Opstal, Ilse Feenstra, Joris van Drongelen, Alex J Eggink, Karin E M Diderich, Philip L J DeKoninck","doi":"10.1002/pd.6622","DOIUrl":"10.1002/pd.6622","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the diagnostic yield of exome sequencing (ES) in fetuses and neonates with prenatally detected congenital diaphragmatic hernia (CDH) and normal copy number variant (CNV) analysis.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of prenatally diagnosed CDH cases seen between 2019 and 2022. All cases who underwent prenatal or postnatal genetic testing were reviewed. The results from the ES analysis that identified pathogenic or likely pathogenic single nucleotide variants are described.</p><p><strong>Results: </strong>In total, 133 fetuses with CDH were seen, of whom 98 (74%) had an isolated CDH and 35 (26%) had a complex CDH (associated structural anomalies) on prenatal examination. ES was performed in 68 cases, and eight pathogenic or likely pathogenic variants were found, accounting for a 12% diagnostic yield (10% [5/50] in isolated cases and 17% [3/18] in complex CDH).</p><p><strong>Conclusions: </strong>In 12% of fetuses and neonates with CDH and normal CNV analysis results, pathogenic or likely pathogenic variants were identified with ES. These data indicate that there is a substantial diagnostic yield when offering ES in prenatally detected CDH, both in complex and isolated cases.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1288-1295"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306684","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":"Reversal of Fetal Compromise Following In Utero Treatment of Vein of Galen Malformation Using Glue.","authors":"Mamatha Gowda, Ariharan Krishnaraj, Murugesan Ambalakkuthan, Navya Chinta, Tamil Selvan","doi":"10.1002/pd.6662","DOIUrl":"10.1002/pd.6662","url":null,"abstract":"<p><strong>Objective: </strong>To treat the fetus presenting with in utero compromise due to a large vein of Galen malformation (VOGM) using glue embolization.</p><p><strong>Methods: </strong>The fetus that was referred for termination of pregnancy at 30 weeks of gestation due to severe cardiomegaly, mild pericardial effusion and large VOGM was evaluated using ultrasound. There was reversed end diastolic flow in the umbilical artery Doppler indicating imminent fetal demise in the premature fetus weighing <1200 g. Considering the request of parents, a treatment similar to recently reported cases of VOGM embolization in utero was attempted as an emergency procedure to salvage the baby. Due to unavailability of coils, financial constraints and urgent need for intervention, n-butyl cyanoacrylate glue with lipiodol was used to embolize the venous outflow of VOGM outflow under ultrasonographic guidance.</p><p><strong>Results: </strong>There was immediate correction of the umbilical artery Doppler waveform with the establishment of a normal flow pattern. The cardiomegaly resolved over 3 weeks and fetal MRI done 2 weeks later showed normal brain architecture with no evidence of hemorrhage or infarction. Pregnancy was continued for 4 weeks after the procedure and terminated at 36 weeks. A female baby weighing 1900 g was delivered by Cesarean section with an Apgar of 8/10. Though initially the baby did well, with mild ventriculomegaly reported on postnatal day 5, she eventually presented at 3 months of age with cardiac failure. As the MRI showed encephalomalacia, due to uncertainty of neurological outcome, further treatment was not pursued by the parents and the baby died a few days later.</p><p><strong>Conclusion: </strong>To our knowledge, this is the first report on the use of glue to treat VOGM prenatally. Though technically successful in correcting the in utero compromise, the baby eventually expired. Cases of in utero embolization using coils and glue have shown success in reversing prenatal pathology and improving survival. However, long-term outcomes including neurological status are yet to be reported.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1367-1371"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146179","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":"Abstracts of the ISPD 28th International Conference on Prenatal Diagnosis and Therapy, 7-10 July 2024, Boston.","authors":"","doi":"10.1002/pd.6665","DOIUrl":"10.1002/pd.6665","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":"44 Suppl 2 ","pages":"3-22"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472962","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":"Characterization of the Prenatal Ultrasound Phenotype Associated With 7q11.23 Microduplication Syndrome and Williams-Beuren Syndrome.","authors":"Fengyang Wang, Huijuan Peng, Guiyu Lou, Yanxin Ren, Shixiu Liao","doi":"10.1002/pd.6669","DOIUrl":"10.1002/pd.6669","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to characterize the intrauterine phenotype of fetuses with 7q11.23 microduplication syndrome and Williams-Beuren syndrome (WBS) to provide insight into prenatal genotype and phenotype correlations in the 7q11.23 region.</p><p><strong>Methods: </strong>Seven fetuses with 7q11.23 microduplication syndrome and sixteen with WBS were diagnosed via array comparative genomic hybridization (array CGH) or copy number variation sequencing (CNV-seq) at our center. Clinical data were also systematically collected and analyzed, including intrauterine phenotype, pregnancy outcome, and inheritance.</p><p><strong>Results: </strong>In our cases, the most common prenatal ultrasound feature of 7q11.23 microduplication syndrome was cardiovascular defects; less frequent features included choroid plexus cysts, anencephaly, bilateral pyelectasis, and cervical lymphatic hygroma. On the other hand, WBS was mainly associated with cardiovascular defects and intrauterine growth retardation. Other clinical phenotypes included hypoechoic frontal horn of the right lateral ventricle, crossed fused renal ectopia, hyperechogenic bowel, hyperechogenic right thoracic cavity, and hyperechogenic hepatic parenchyma/intrahepatic duct wall.</p><p><strong>Conclusions: </strong>Our study describes a series of new ultrasound features identified prenatally in fetuses with 7q11.23 microduplications and microdeletions with the intent of expanding the prenatal phenotype associated with copy number variants in this chromosomal region. Additional studies are needed to clearly delineate specific prenatal features associated with these rare genetic entities.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1398-1411"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293743","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":"Customizing carrier screening in the Chinese population: Insights from a 334-gene panel.","authors":"Sha Liu, Shuang Huang, Victor Wei Zhang, Liyuan Cao, Haipeng Liu, Xiang Wei, Yuan Luo, Yue Li, Lin Zhou, Fuping Li, Qian Zhu, Hongqian Liu","doi":"10.1002/pd.6635","DOIUrl":"10.1002/pd.6635","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the yield and applicability of expanded carrier screening and propose carrier rate screening thresholds suitable for the Chinese population by comparing the current screening panel with the American College of Medical Genetics and Genomics recommended panel of 113 genes.</p><p><strong>Methods: </strong>Using targeted next-generation sequencing, a customized panel with 334 genes was performed on 2168 individuals without clinical phenotypes for expanded carrier screening purpose. Variant interpretation followed the American College of Medical Genetics and Genomics guidelines. Carrier rates were calculated for each identified variant and each gene. At-risk couple rates were also assessed. The yield of expanded carrier screening was evaluated through calculating cumulative carrier rate.</p><p><strong>Results: </strong>Overall, 65.87% of the individuals were found to be carriers of at least 1 disease causing variants. The overall at-risk couple rate was 11.76%, of which the GJB2:c.109G > A related at-risk couple rate was 5.78%. The cumulative carrier rate of 334-panel was 65.53%. When screened genes with gene carrier rate ≥1/1000, the expanded carrier screening can cover over 90% of the cumulative carrier rate and at-risk couples. A total of 86 genes overlapped with American College of Medical Genetics and Genomics Tier-3 genes and were attributed to the cumulative carrier rate of 47.33%.</p><p><strong>Conclusion: </strong>Expanded carrier screening using the 334-gene panel showed high screening efficiency. A threshold of gene carrier rate ≥1/1000 is recommended for selecting carrier screening genes in the Chinese Han population. This study highlights the importance of customizing screening panels based on the ACMG Tier-3 genes in conjunction with population-specific carrier frequencies to improve the accuracy and effectiveness of expanded carrier screening.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1335-1343"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731333","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":"Experimental Induction of Complex Gastroschisis in the Fetal Lamb: Systematic Review.","authors":"Tomohiro Arai, Wasinee Tianthong, Francesca Maria Russo, David Basurto, Luc Joyeux, Paolo De Coppi, Jan Deprest","doi":"10.1002/pd.6647","DOIUrl":"10.1002/pd.6647","url":null,"abstract":"<p><p>We systematically reviewed experiments in the fetal lamb model of gastroschisis using PubMed, Embase, Web of Science, and Scopus, seeking for standardized surgical techniques to obtain complex gastroschisis. Eligible were studies where an abdominal wall defect was surgically induced and gross anatomical findings at birth were available. The primary outcome was complex gastroschisis, defined by the presence of bowel stenosis, atresia, volvulus, perforation, and/or necrosis. Secondary outcomes were fetal death and additional readouts reported. Of ten eligible studies, six included lambs that had no additional prenatal manipulations and were assessed at term (35 lambs). Gastroschisis was induced at day 70-80 (term = 140-145), typically (n = 4/6 studies) in the left lower abdomen with defect size ranging from 0.5 to 4.0 cm. Only one study, in which a 1.5 cm diameter silicone ring was utilized, resulted in complex gastroschisis in 100% of term survivors. Fetal loss was more frequent in studies where a silicone ring and/or a right-sided defect were used. No changes unique to complex gastroschisis were identified in additional readouts, including bowel histology. When gastroschisis becomes \"complex\" following induction is uncertain. This knowledge is essential in studying potential prenatal interventions that may change the natural course.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1372-1380"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047050","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":"Second-Trimester Ultrasound Receipt Mediates the Relationship Between Public Insurance and Prenatal Diagnosis of a Congenital Heart Defect.","authors":"Joyce L Woo, Rupali Gandhi, Christina Laternser, Tara Iyengar, Lynn M Yee, William A Grobman, Matthew M Davis, Angira Patel, Joyce T Johnson","doi":"10.1002/pd.6675","DOIUrl":"https://doi.org/10.1002/pd.6675","url":null,"abstract":"<p><strong>Objective: </strong>To delineate the mechanism behind insurance-related disparities in the prenatal diagnosis of a congenital heart defect (CHD).</p><p><strong>Methods: </strong>This was a retrospective analysis of electronic health records of pregnant individuals whose infants received CHD surgery between 2019 and 2020 in the third-largest United States metropolitan area. The outcome was whether a prenatal diagnosis was received. The exposure was the pregnant individual's insurance status. The mediator was second-trimester ultrasound receipt. Control variables included sociodemographic and clinical characteristics of the pregnant individual and infant. The relationships between exposure, mediator, and outcome were quantified using mediation analysis with multivariable fixed-effects regression.</p><p><strong>Results: </strong>In total, 496 pregnant individuals met inclusion criteria; 215 (43.3%) were publicly insured and 305 (61.5%) had prenatal diagnosis. In bivariate regressions, public insurance was associated with a 12.6% lower probability (CI 3%-21%) of prenatal diagnosis. In multivariable models, public insurance was associated with 13.2% lower probability (CI 2%-25%) of second-trimester ultrasound receipt but was no longer associated with prenatal diagnosis after adjusting for second-trimester ultrasound receipt, suggesting a possible mediation effect. Mediation analysis confirmed that second-trimester ultrasound receipt mediated 39% of the relationship between public insurance and prenatal diagnosis.</p><p><strong>Conclusion: </strong>An appreciable portion of insurance-related differences in prenatal CHD diagnosis is due to the lower frequency of second-trimester ultrasound receipt among those with public insurance.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293747","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":"Response to Wynn and Hokovec Regarding “The Use of cfDNA to Screen for Monogenic Conditions in Low Risk Populations Is Ready for Clinical Use”","authors":"Neeta L. Vora, Sylvie Langlois, Lyn S. Chitty","doi":"10.1002/pd.6656","DOIUrl":"https://doi.org/10.1002/pd.6656","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":"27 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265444","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}