International Journal of Neonatal Screening最新文献

Outcomes of a Pilot Newborn Screening Program for Spinal Muscular Atrophy in the Valencian Community.

IF 4

International Journal of Neonatal Screening Pub Date : 2025-01-14 DOI: 10.3390/ijns11010007

Alba Berzal-Serrano, Belén García-Bohórquez, Elena Aller, Teresa Jaijo, Inmaculada Pitarch-Castellano, Dolores Rausell, Gema García-García, José M Millán

{"title":"Outcomes of a Pilot Newborn Screening Program for Spinal Muscular Atrophy in the Valencian Community.","authors":"Alba Berzal-Serrano, Belén García-Bohórquez, Elena Aller, Teresa Jaijo, Inmaculada Pitarch-Castellano, Dolores Rausell, Gema García-García, José M Millán","doi":"10.3390/ijns11010007","DOIUrl":"10.3390/ijns11010007","url":null,"abstract":"Spinal muscular atrophy (SMA) is a degenerative neuromuscular condition resulting from a homozygous deletion of the survival motor neuron 1 (SMN1) gene in 95% of patients. A timely diagnosis via newborn screening (NBS) and initiating treatment before the onset of symptoms are critical for improving health outcomes in affected individuals. We carried out a screening test by quantitative PCR (qPCR) to amplify the exon seven of SMN1 using dried blood spot (DBS) samples. From October 2021 to August 2024, a total of 31,560 samples were tested in the Valencian Community (Spain) and 4 of them were positive for SMA, indicating an incidence of 1/7890. Genetic confirmation was performed using multiplex ligation-dependent probe amplification (MLPA) and AmplideX PCR/CE SMN1/2 Plus kit, in parallel obtaining concordant results in survival motor neuron 2 (SMN2) gene copy number. Within the first few weeks of their lives, two of the four patients detected by NBS showed signs of severe hypotonia, becoming ineligible for treatment. The other two patients were the first presymptomatic patients with two copies of SMN2 to receive treatment with Risdiplam in Spain. In order to treat positive cases in their early stages, we conclude that the official deployment of SMA newborn screening is necessary.","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"11 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Training and Evaluation of the "Dual-Index" Screening Method for Neonatal Congenital Heart Disease: A Multi-Center Study in China.

IF 4

International Journal of Neonatal Screening Pub Date : 2025-01-14 DOI: 10.3390/ijns11010008

Panpan Huang, Qing Gu, Xiaoting Zhu, Ijaz Ul Haq, Liling Li, Xiaojing Hu, Guoying Huang

{"title":"The Training and Evaluation of the \"Dual-Index\" Screening Method for Neonatal Congenital Heart Disease: A Multi-Center Study in China.","authors":"Panpan Huang, Qing Gu, Xiaoting Zhu, Ijaz Ul Haq, Liling Li, Xiaojing Hu, Guoying Huang","doi":"10.3390/ijns11010008","DOIUrl":"10.3390/ijns11010008","url":null,"abstract":"Background: This study aimed to enhance the scope of neonatal congenital heart disease (CHD) screening by evaluating the effectiveness of training personnel in CHD screening using the \"dual-index\" method, combining pulse oximetry with cardiac murmur auscultation.Methods: From 2019 to 2022, a total of 2374 screening personnel from the Xinjiang, Yunnan, Hainan, Fujian, and Anhui provinces underwent training in neonatal CHD screening using the \"dual-index\" method, which involves pulse oximetry and cardiac murmur auscultation. Pre- and post-training assessments were conducted using a neonatal CHD screening knowledge questionnaire, distributed through the Questionnaire Star platform, to evaluate the impact of the training. The annual neonatal CHD screening rates were consistently recorded in these five provinces during the same period to assess the increase in screening coverage.Results: After the training, the screening personnel exhibited a significantly improved understanding of the neonatal CHD screening method (p < 0.001). Additionally, the professional background (t = -8.007, p < 0.001) and years of experience (t = 2.839, p = 0.005) of the screening personnel were identified as independent factors influencing their screening knowledge. During the same period, there was consistent linear growth in the screening coverage rate for neonatal CHD across the five provinces (χ2 = 121065.416, p < 0.001).Conclusion: Standardized training in the \"dual-index\" method, incorporating pulse oximetry and cardiac murmur auscultation, for screening personnel significantly enhances their screening knowledge, thereby playing a critical role in expanding the coverage of neonatal CHD screening.","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"11 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS/MS Proteomic Assay for Wilson Disease and Inborn Errors of Immunity.

IF 4

International Journal of Neonatal Screening Pub Date : 2025-01-10 DOI: 10.3390/ijns11010006

Claire Klippel, Jiwoon Park, Sean Sandin, Tara M L Winstone, Xue Chen, Dennis Orton, Aranjeet Singh, Jonathan D Hill, Tareq K Shahbal, Emily Hamacher, Brandon Officer, John Thompson, Phi Duong, Tim Grotzer, Si Houn Hahn

{"title":"Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS/MS Proteomic Assay for Wilson Disease and Inborn Errors of Immunity.","authors":"Claire Klippel, Jiwoon Park, Sean Sandin, Tara M L Winstone, Xue Chen, Dennis Orton, Aranjeet Singh, Jonathan D Hill, Tareq K Shahbal, Emily Hamacher, Brandon Officer, John Thompson, Phi Duong, Tim Grotzer, Si Houn Hahn","doi":"10.3390/ijns11010006","DOIUrl":"10.3390/ijns11010006","url":null,"abstract":"For many genetic disorders, there are no specific metabolic biomarkers nor analytical methods suitable for newborn population screening, even where highly effective preemptive treatments are available. The direct measurement of signature peptides as a surrogate marker for the protein in dried blood spots (DBSs) has been shown to successfully identify patients with Wilson Disease (WD) and three life-threatening inborn errors of immunity, X-linked agammaglobulinemia (XLA), Wiskott-Aldrich syndrome (WAS), and adenosine deaminase deficiency (ADAD). A novel proteomic-based multiplex assay to detect these four conditions from DBS using high-throughput LC-MS/MS was developed and validated. The clinical validation results showed that the assay can accurately identify patients of targeted disorders from controls. Additionally, 30,024 newborn DBS samples from the Washington State Department of Health Newborn Screening Laboratory have been screened from 2022 to 2024. One true presumptive positive case of WD was found along with three false positive cases. Five false positives for WAS were detected, but all of them were premature and/or low-birth-weight babies and four of them had insufficient DNA for confirmation. The pilot study demonstrates the feasibility and effectiveness of utilizing this multiplexed proteomic assay for newborn screening.","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"11 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development, Validation, and Application of the Paya Hamsan Technologies Underivatized Newborn Screening Assay (PHUNSA) for Inborn Metabolic Disorders in Dried Blood Spot Samples from Iranian Infants.

IF 4

International Journal of Neonatal Screening Pub Date : 2025-01-08 DOI: 10.3390/ijns11010004

Azam Khodadadi, Saber Nanbedeh, Mahsa Joodaki, Bradford L Therrell, Kambiz Gilany

{"title":"Development, Validation, and Application of the Paya Hamsan Technologies Underivatized Newborn Screening Assay (PHUNSA) for Inborn Metabolic Disorders in Dried Blood Spot Samples from Iranian Infants.","authors":"Azam Khodadadi, Saber Nanbedeh, Mahsa Joodaki, Bradford L Therrell, Kambiz Gilany","doi":"10.3390/ijns11010004","DOIUrl":"10.3390/ijns11010004","url":null,"abstract":"Screening for inborn metabolic disorders (IMDs) in newborns is an important way to prevent serious metabolic and developmental difficulties that can result in lasting disabilities or even death. Electrospray ionization tandem mass spectrometry (MS/MS) provides an efficacious newborn blood spot screening (NBS) mechanism for analyzing dried blood spot specimens (DBSs) for biochemical markers for these conditions. Where possible, the elimination of derivatization in specimen preparation can simplify and streamline analysis. The Paya Hamsan Technologies Underivatized Newborn Screening Assay (PHUNSA) is an underivatized MS/MS test kit for IMD NBS. Validation of the accuracy, precision, linearity, and stability was based on the ISO 15189 standard and the CLSI NBS04 guideline. The PHUNSA kit demonstrated suitable performance along with acceptable recovery rates and negligible bias for many IMD analytes. Assay sensitivity was demonstrated through acceptable limits of detection (LOD) and lower limits of quantification (LLOQ). Specimen preparation times were decreased, the coefficients of variation were consistently below 10%, and accuracy and stability were demonstrated under various testing conditions, including prolonged storage and transportation. The PHUNSA kit provides a simplified, efficient, and reliable approach to IMD NBS with the potential to enhance NBS in Iran and other locations by providing a scalable, cost-effective, and streamlined option for early IMD detection and management.","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"11 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Maternity Care Providers' Experiences with Providing Information on Newborn Bloodspot Screening During Pregnancy: A Dutch Survey Study.

IF 4

International Journal of Neonatal Screening Pub Date : 2025-01-08 DOI: 10.3390/ijns11010005

Jasmijn E Klapwijk, Janneke Gitsels-van der Wal, Linda Martin, Rendelien K Verschoof-Puite, Ellen Elsinghorst, Lidewij Henneman

{"title":"Maternity Care Providers' Experiences with Providing Information on Newborn Bloodspot Screening During Pregnancy: A Dutch Survey Study.","authors":"Jasmijn E Klapwijk, Janneke Gitsels-van der Wal, Linda Martin, Rendelien K Verschoof-Puite, Ellen Elsinghorst, Lidewij Henneman","doi":"10.3390/ijns11010005","DOIUrl":"10.3390/ijns11010005","url":null,"abstract":"Newborn bloodspot screening (NBS) aims to detect treatable disorders in newborns to offer early interventions. According to the official Dutch national NBS guidance, parents in the Netherlands should be informed about NBS during pregnancy by maternity care providers (MCPs), providing two leaflets and oral information. This study investigated what, how, and when information about NBS is given during pregnancy according to Dutch MCPs. An online questionnaire was completed by 279 MCPs; 237 (84.9%) provided information to parents themselves, although 4.6% of them only did so postnatally, and 240 (86.0%) considered this the task of the MCP. Among the 237 MCPs, information was provided by personal conversation (59.9%) and by giving at least one leaflet (83.1%), while 25.7% only gave leaflets. Being a first pregnancy (45.1%) and parents' literacy (38.8%) influenced how MCPs provided information. Information was mostly provided at 34-37 weeks gestation (68.8%). Conversations mostly included giving information on when NBS will be performed (97.2%), the purpose of NBS (93.7%), how the test will be performed (92.3%), and participation being voluntary (80.3%). The results suggest that while most Dutch MCPs consider it their task to provide NBS information, its timing, method, and completeness do not always follow the established guidelines.","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"11 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Parent Reports of Developmental Service Utilization After Newborn Screening.

IF 4

International Journal of Neonatal Screening Pub Date : 2024-12-31 DOI: 10.3390/ijns11010003

Elizabeth Reynolds, Sarah Nelson Potter, Samantha Scott, Donald B Bailey

{"title":"Parent Reports of Developmental Service Utilization After Newborn Screening.","authors":"Elizabeth Reynolds, Sarah Nelson Potter, Samantha Scott, Donald B Bailey","doi":"10.3390/ijns11010003","DOIUrl":"10.3390/ijns11010003","url":null,"abstract":"Newborn screening (NBS) presents an opportunity to identify a subset of babies at birth who are at risk for developmental delays and could benefit from a range of developmental services. Potential developmental services in the United States include Part C Early Intervention (EI), private therapies, and school-based services. Using parent-reported outcomes, this study examined the rates at which a sample of children diagnosed with NBS conditions used each developmental service. An online survey of 153 parents representing children with 27 different NBS conditions found that nearly 75% of children (n = 112) used at least one developmental service, with private therapies being the most frequent. Children were referred to EI relatively early and were often eligible because their medical diagnosis automatically qualified them. When examining condition-specific results for children with severe combined immunodeficiencies, congenital hypothyroidism, and Pompe disease, we found variability in rates of use, with high rates overall. Our findings suggest that many children diagnosed with an NBS condition continue to have developmental delays even after they receive appropriate medical care. Future research with more systematic follow-up is needed to understand whether the NBS program facilitates entry into these services and whether more streamlined processes could benefit children and families.","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"11 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Consolidated Newborn Bloodspot Screening Efforts in Developing Countries in the Asia Pacific-2024.

IF 4

International Journal of Neonatal Screening Pub Date : 2024-12-30 DOI: 10.3390/ijns11010002

Bradford L Therrell, Carmencita D Padilla, Michelle E Abadingo, Shree Prasad Adhikari, Thuza Aung, Thet Thet Aye, Sanjoy Kumer Dey, Muhammad Faizi, Erdenetuya Ganbaatar, Tran Thi Huong Giang, Hoang Thu Hang, Rathmony Heng, Seema Kapoor, Khurelbaatar Nyamdavaa, Prajwal Paudel, Kimyi Phou, Aman B Pulungan, Chittaphone Sayyavong, Salimah R Walani, Tariq Zafar

{"title":"Consolidated Newborn Bloodspot Screening Efforts in Developing Countries in the Asia Pacific-2024.","authors":"Bradford L Therrell, Carmencita D Padilla, Michelle E Abadingo, Shree Prasad Adhikari, Thuza Aung, Thet Thet Aye, Sanjoy Kumer Dey, Muhammad Faizi, Erdenetuya Ganbaatar, Tran Thi Huong Giang, Hoang Thu Hang, Rathmony Heng, Seema Kapoor, Khurelbaatar Nyamdavaa, Prajwal Paudel, Kimyi Phou, Aman B Pulungan, Chittaphone Sayyavong, Salimah R Walani, Tariq Zafar","doi":"10.3390/ijns11010002","DOIUrl":"10.3390/ijns11010002","url":null,"abstract":"Approximately half of all births globally occur in the Asia Pacific Region. Concerted efforts to support local activities aimed at developing national newborn screening (NBS) have been ongoing for almost 30 years, first by the International Atomic Energy Agency (IAEA) and then through volunteer efforts. Sustainable newborn bloodspot screening (NBS) continues to be initiated and develop in many of the countries with developing economies in the region. Since the discontinuation of IAEA funding in 2007, a working group of the Asia Pacific Society of Human Genetics (APSHG) consisting of interested representatives from countries in the region with less than 50% NBS coverage has participated in periodic workshops to exchange information, set goals, and provide peer support. Facilitated by international NBS experts, interested corporate sponsors, and the APSHG, the 7th workshop of representatives from 10 East Asian countries with developing NBS systems was recently held in Kathmandu, Nepal. This report summarizes the NBS activities in these countries and describes the continuing efforts to move NBS ahead in the region.","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"11 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability.

IF 4

International Journal of Neonatal Screening Pub Date : 2024-12-28 DOI: 10.3390/ijns11010001

Abigail Veldman, Birgit Sikkema-Raddatz, Terry G J Derks, Clara D M van Karnebeek, M B Gea Kiewiet, Margaretha F Mulder, Marcel R Nelen, M Estela Rubio-Gozalbo, Richard J Sinke, Monique G de Sain-van der Velden, Gepke Visser, Maaike C de Vries, Dineke Westra, Monique Williams, Ron A Wevers, M Rebecca Heiner-Fokkema, Francjan J van Spronsen

{"title":"Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability.","authors":"Abigail Veldman, Birgit Sikkema-Raddatz, Terry G J Derks, Clara D M van Karnebeek, M B Gea Kiewiet, Margaretha F Mulder, Marcel R Nelen, M Estela Rubio-Gozalbo, Richard J Sinke, Monique G de Sain-van der Velden, Gepke Visser, Maaike C de Vries, Dineke Westra, Monique Williams, Ron A Wevers, M Rebecca Heiner-Fokkema, Francjan J van Spronsen","doi":"10.3390/ijns11010001","DOIUrl":"10.3390/ijns11010001","url":null,"abstract":"The biomarker-based Dutch Newborn Screening (NBS) panel (as of 2024) comprises 19 inherited metabolic disorders (IMDs). With the use of next-generation sequencing (NGS) as a first-tier screen, NBS could expand to include IMDs that lack a reliable biochemical footprint in dried blood spots, while also reducing secondary findings. To be eligible for inclusion in NBS, an IMD needs to fulfill the Wilson and Jungner criteria, with treatability being one of the most important criteria. In this study, we aimed to identify IMDs eligible for DNA-first NBS when considering only treatability in the context of NBS as a prerequisite. First, three independent reviewers performed a systematic literature review of the 1459 genotypic IMDs and their causative gene(s), as described in the International Classification of Inherited Metabolic Disorders (dated 1 February 2021), applying 16 criteria to exclude non-treatable disorders. Eligible disorders were then discussed in three online meetings with a project group of clinical laboratory geneticists, medical laboratory specialists specialized in IMD, and pediatricians with expertise in IMDs. Based on treatability, we identified 100 genes, causing 95 IMDs, as eligible for NBS, including 42 causal genes for the IMDs in the current biomarker-based NBS. The other 58 genes are primarily associated with treatable defects in amino acid metabolism and fatty acid oxidation. Other IMDs were excluded, most often because of insufficient literature. As the evaluation of treatability was not straightforward, we recommend the development of standardized treatability scores for the inclusion of IMDs in NBS.","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"11 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Digital-Tier Strategy Improves Newborn Screening for Glutaric Aciduria Type 1. 数字层策略改善新生儿戊二酸尿1型筛查。

IF 4

International Journal of Neonatal Screening Pub Date : 2024-12-21 DOI: 10.3390/ijns10040083

Elaine Zaunseder, Julian Teinert, Nikolas Boy, Sven F Garbade, Saskia Haupt, Patrik Feyh, Georg F Hoffmann, Stefan Kölker, Ulrike Mütze, Vincent Heuveline

{"title":"Digital-Tier Strategy Improves Newborn Screening for Glutaric Aciduria Type 1.","authors":"Elaine Zaunseder, Julian Teinert, Nikolas Boy, Sven F Garbade, Saskia Haupt, Patrik Feyh, Georg F Hoffmann, Stefan Kölker, Ulrike Mütze, Vincent Heuveline","doi":"10.3390/ijns10040083","DOIUrl":"10.3390/ijns10040083","url":null,"abstract":"Glutaric aciduria type 1 (GA1) is a rare inherited metabolic disease increasingly included in newborn screening (NBS) programs worldwide. Because of the broad biochemical spectrum of individuals with GA1 and the lack of reliable second-tier strategies, NBS for GA1 is still confronted with a high rate of false positives. In this study, we aim to increase the specificity of NBS for GA1 and, hence, to reduce the rate of false positives through machine learning methods. Therefore, we studied NBS profiles from 1,025,953 newborns screened between 2014 and 2023 at the Heidelberg NBS Laboratory, Germany. We identified a significant sex difference, resulting in twice as many false-positives male than female newborns. Moreover, the proposed digital-tier strategy based on logistic regression analysis, ridge regression, and support vector machine reduced the false-positive rate by over 90% compared to regular NBS while identifying all confirmed individuals with GA1 correctly. An in-depth analysis of the profiles revealed that in particular false-positive results with high associated follow-up costs could be reduced significantly. In conclusion, understanding the origin of false-positive NBS and implementing a digital-tier strategy to enhance the specificity of GA1 testing may significantly reduce the burden on newborns and their families from false-positive NBS results.","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"10 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11679506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of Neonatal Screening Programs for Tyrosinemia Type 1 Worldwide. 评价新生儿筛查方案酪氨酸血症1型世界各地。

IF 4

International Journal of Neonatal Screening Pub Date : 2024-12-16 DOI: 10.3390/ijns10040082

Allysa M Kuypers, Marelle J Bouva, J Gerard Loeber, Anita Boelen, Eugenie Dekkers, Konstantinos Petritis, C Austin Pickens, The Isns Representatives, Francjan J van Spronsen, M Rebecca Heiner-Fokkema

{"title":"Evaluation of Neonatal Screening Programs for Tyrosinemia Type 1 Worldwide.","authors":"Allysa M Kuypers, Marelle J Bouva, J Gerard Loeber, Anita Boelen, Eugenie Dekkers, Konstantinos Petritis, C Austin Pickens, The Isns Representatives, Francjan J van Spronsen, M Rebecca Heiner-Fokkema","doi":"10.3390/ijns10040082","DOIUrl":"10.3390/ijns10040082","url":null,"abstract":"In The Netherlands, newborn screening (NBS) for tyrosinemia type 1 (TT1) uses dried blood spot (DBS) succinylacetone (SUAC) as a biomarker. However, high false-positive (FP) rates and a false-negative (FN) case show that the Dutch TT1 NBS protocol is suboptimal. In search of optimization options, we evaluated the protocols used by other NBS programs and their performance. We distributed an online survey to NBS program representatives worldwide (N = 41). Questions focused on the organization and performance of the programs and on changes since implementation. Thirty-three representatives completed the survey. TT1 incidence ranged from 1/13,636 to 1/750,000. Most NBS samples are taken between 36 and 72 h after birth. Most used biomarkers were DBS SUAC (78.9%), DBS Tyrosine (Tyr; 5.3%), or DBS Tyr with second tier SUAC (15.8%). The pooled median cut-off for SUAC was 1.50 µmol/L (range 0.3-7.0 µmol/L). The median cut-off from programs using laboratory-developed tests was significantly higher (2.63 µmol/L) than the medians from programs using commercial kits (range 1.0-1.7 µmol/L). The pooled median cut-off for Tyr was 216 µmol/L (range 120-600 µmol/L). Overall positive predictive values were 27.3% for SUAC, 1.2% for Tyr solely, and 90.1% for Tyr + SUAC. One FN result was reported for TT1 NBS using SUAC, while three FN results were reported for TT1 NBS using Tyr. The NBS programs for TT1 vary worldwide in terms of analytical methods, biochemical markers, and cut-off values. There is room for improvement through method standardization, cut-off adaptation, and integration of new biomarkers. Further enhancement is likely to be achieved by the application of post-analytical tools.","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"10 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11677071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0