International Journal of Neonatal Screening最新文献

{"title":"Newborn Screening for Spinal Muscular Atrophy in the Republic of Moldova: A Feasibility Study and First Steps.","authors":"Iulia Coliban, Natalia Usurelu, Igor Opalco, Sergiu Gladun, Victoria Sacara","doi":"10.3390/ijns12020038","DOIUrl":"10.3390/ijns12020038","url":null,"abstract":"<p><p>Spinal muscular atrophy (SMA) is a severe neuromuscular disorder in which presymptomatic treatment substantially improves survival and motor outcomes, yet newborn screening for SMA remains unevenly implemented across Europe, and evidence from lower-resource health systems is needed to guide scale-up. In this study, we assessed the feasibility, diagnostic performance, and public health implications of implementing neonatal SMA screening in the Republic of Moldova within an established national newborn screening framework. A pilot genetic screening program was conducted using dried blood spot (DBS) samples collected through routine newborn screening workflows; <i>SMN1</i> exon 7 deletion testing was performed by real-time polymerase chain reaction (qPCR), and positive findings were confirmed by multiplex ligation-dependent probe amplification (MLPA), alongside the evaluation of operational integration and system-level requirements. Screening was operationally feasible within existing DBS processes and demonstrated high analytical performance, consistent with published international experience, although performance results should be interpreted cautiously due to the limited sample size. Two SMA cases were confirmed in a small cohort, enabling early diagnosis and timely referral for disease-modifying therapy, and integration into the existing program was practical and resource-efficient. These findings support the incorporation of SMA into national newborn screening panels using DBS-based molecular methods, highlighting an implementable model for introducing advanced genetic testing within routine public health services.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13299184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317098","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}

{"title":"A Prospective Multi-Center Newborn Screening for Thalassemia by Comprehensive Analysis of Thalassemia Alleles (CATSA) Based on Single Molecule Real-Time Sequencing in Guangxi, China.","authors":"Aihua Xia, Hongfei Chen, Fuhua Lu, Ping Xu, Peixiao Shen, Wei Wei, Chunrong Gui, Juliang Liu, Dan Wei, Haipeng Qin, Yan Huang, Ju Long, Baoheng Gui","doi":"10.3390/ijns12020037","DOIUrl":"10.3390/ijns12020037","url":null,"abstract":"<p><p>Thalassemia is one of the most common inherited diseases in Guangxi, China. Early identification of thalassemia by neonatal screening is beneficial for effective clinical management and treatment. A total of 3671 newborns from multiple centers of Guangxi were prospectively recruited and screened for thalassemia using single molecule real-time (SMRT) sequencing technology. A total of 36 types of variants of globin genes were identified, including 16 common variants and 20 rare variants in the Chinese population. In total, 956 (26.04%) newborns were identified to carry thalassemia variants, including 672 (18.31%) α-thalassemia, 228 (6.21%) β-thalassemia, 55 (1.50%) combined α/β-thalassemia and 1 (0.03%) δ-thalassemia. In addition, this study showed that the carrier rates of structural variants of α-globin genes and abnormal hemoglobin variants were 1.28% and 0.93% respectively. Phenotypically, 12 newborns with hemoglobin H disease and 2 cases with intermedia β-thalassemia were found, two of whom would be misdiagnosed by conventional genetic analysis methods. Collectively, this study characterized the complexity and diversity of thalassemia gene variants in newborns of Guangxi, and further achieved early identification of newborns with intermedia thalassemia, which facilitated precision prevention of thalassemia in this region. Also, SMRT provided a powerful tool for neonatal thalassemia screening, especially in prevalent regions.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13262897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030382","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}

{"title":"Comparison of Four Screening Markers [(C16 + C18:1)/C2, C14/C3, C12/C0, and C12/C2] for Carnitine Palmitoyltransferase II Deficiency in the Nationwide Newborn Screening Program in Japan.","authors":"Go Tajima, Nobuyuki Ishige, Junji Hanai, Keiko Konomura","doi":"10.3390/ijns12020036","DOIUrl":"10.3390/ijns12020036","url":null,"abstract":"<p><p>False-positive results are known to occur frequently in newborn screening (NBS) for carnitine palmitoyltransferase II (CPT II) deficiency, highlighting the need to identify appropriate screening markers. The present study aimed to compare the performance of two markers currently used in NBS for CPT II deficiency, (C16 + C18:1)/C2 and C14/C3, with two promising alternative markers, C12/C0 and C12/C2. We analyzed non-patient data from the 2023 fiscal year NBS program together with patient data for CPT II deficiency and very-long-chain acyl-CoA dehydrogenase deficiency derived from previously reported case series. Marker performance was assessed using precision-recall curves, including an analysis in which patients with the myopathic form of CPT II deficiency who passed NBS using (C16 + C18:1)/C2 and C14/C3 were reclassified as true positives. The area under the precision-recall curve values for C12/C2 and C14/C3 were 0.711 (95% confidence interval, 0.492-0.923) and 0.569 (0.341-0.779), respectively, indicating superior performance compared with the other markers. When cases with the myopathic form of CPT II deficiency were included as true positives, the performance of all markers decreased markedly. Although some patients with the myopathic form are still likely to be missed, C12/C2 appears to be an effective marker for reducing false-positive results.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030443","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}

{"title":"Newborn Screening in Saudi Arabia: Brief History, Current Practice, and Future Direction.","authors":"Ahmed H Mujamammi","doi":"10.3390/ijns12020035","DOIUrl":"10.3390/ijns12020035","url":null,"abstract":"<p><p>The Saudi Arabia National Newborn Screening (NBS) program is a pillar of public health, offering timely detection of treatable, life-threatening, or disabling conditions in neonates. This comprehensive review critically examines the current laboratory diagnostic practices employed for metabolite analysis within this program. It focuses primarily on biochemical NBS conducted via dried blood spot testing and evaluates the methodologies, technical challenges, and stringent quality assurance measures that underpin successful screening. This review examines the critical role of tandem mass spectrometry, sample integrity protocols, and the establishment of robust cutoff values. Furthermore, this review explores persistent challenges such as false-positive and false-negative results, ethical and logistical hurdles in global implementation, and the transformative potential of recent advancements, including the integration of genomics and high-resolution metabolomics. In addition, this review explores the future of the program, highlighting the transformative potential of high-resolution metabolomics and the integration of genomic sequencing to ensure early diagnosis and intervention.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030410","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}

{"title":"Parents' Experiences of Receiving a Severe Combined Immunodeficiency (SCID) or Non-SCID T-Cell Lymphopenia Outcome During the Newborn Screening Evaluation in England.","authors":"Pru Holder, Chloe Musa, Jim B Chilcott, Anju D Keetharuth, Louise Moody, Ellinor K Olander, Fiona Ulph, Jane Chudleigh","doi":"10.3390/ijns12020034","DOIUrl":"10.3390/ijns12020034","url":null,"abstract":"<p><strong>Background: </strong>In 2021, the UK National Screening Committee commissioned an evaluation of newborn bloodspot screening for severe combined immunodeficiency (SCID) in England. This paper describes the experiences of parents who received an SCID or non-SCID T-cell lymphopenia (non-SCID TCL) result for their baby during the evaluation.</p><p><strong>Methods: </strong>A qualitative exploratory design was employed using semi-structured interviews with 12 parents (<i>n</i> = 5 who had received an SCID outcome and <i>n</i> = 7 who had received a non-SCID TCL following SCID NBS).</p><p><strong>Results: </strong>The impact on parents whose baby was diagnosed with SCID was complex, reflecting the experience of receiving a presymptomatic diagnosis. Parents of babies who had been diagnosed with a non-SCID TCL viewed their baby's result in terms of risk; while their baby might still have a serious immunological condition, it was not considered to be as serious as SCID. All parents reported that they valued their participation in the SCID screening evaluation.</p><p><strong>Conclusions: </strong>Support for families following a positive screening result for SCID needs to be considered. This includes tailored psychosocial support, given their experiences will not be the same as those of parents of non-screened babies with SCID.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030400","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}

{"title":"Conjugated Hyperbilirubinemia in Early Infancy: Rethinking Diagnostic Cut-Offs-A Retrospective Analysis.","authors":"Daniel Pfurtscheller, Carola Ganzer, Ena Suppan, Melina Winkler, Bernhard Schwaberger, Lisa Sallmon, Gerhard Pichler, Benno Kohlmaier","doi":"10.3390/ijns12020033","DOIUrl":"10.3390/ijns12020033","url":null,"abstract":"<p><strong>Background: </strong>Conjugated hyperbilirubinemia in early infancy is a critical indicator of hepatobiliary dysfunction. Prompt and accurate identification is essential to diagnose cholestatic liver disease (CLD), particularly biliary atresia. Current guidelines define conjugated bilirubin (CB) ≥ 1 mg/dL as abnormal, irrespective of total bilirubin (TB). This study aimed to evaluate whether combining absolute and relative CB thresholds improves diagnostic performance for CLD.</p><p><strong>Methods: </strong>We retrospectively analyzed all infants aged ≤6 months of chronological age with CB ≥ 1 mg/dL admitted to the Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria, between January 2004 and February 2025. During that period, 116,104 infants were born at our hospital catchment area; 3119 of these underwent bilirubin fractionation, and 257 infants (0.2% of total births) had a CB ≥ 1 mg/dL and were included in the analysis. Clinical and biochemical data were extracted. Diagnostic performance of the absolute (CB ≥ 1 mg/dL) and in combination with the relative (CB ≥ 20% of TB) thresholds was assessed using receiver operating characteristic (ROC) analysis for the detection of CLD.</p><p><strong>Results: </strong>Among 257 infants, 47 (18%) were diagnosed with CLD. The median age at the time of blood sampling was 18 days (IQR 9-31). The combined criterion (CB ≥ 1 mg/dL and ≥20% of TB) achieved 100% sensitivity and 61.2% specificity (AUC = 0.82, 95% CI 0.79-0.92; <i>p</i> < 0.001). Implementation of the combined cut-off reduced the number needed to screen from 5.5 to 2.7, representing nearly a twofold improvement in diagnostic efficiency.</p><p><strong>Conclusions: </strong>Applying both absolute (≥1 mg/dL) and relative (≥20% of total bilirubin) CB thresholds substantially improves detection of neonatal CLD in early infancy. This combined approach maintains full sensitivity while reducing false positives and unnecessary investigations, thereby enhancing diagnostic efficiency in early infancy.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030471","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}

{"title":"Health-Related Coping Behaviors Among Parents of Children with Inborn Errors of Metabolism: A Survey by Dietary Therapy, Child Age, and Diagnostic Category.","authors":"Yuko Matsumoto, Yuko Kushihashi, Akiko Suwa, Go Tajima","doi":"10.3390/ijns12020032","DOIUrl":"10.3390/ijns12020032","url":null,"abstract":"<p><p>Newborn mass screening improves outcomes for inborn errors of metabolism (IEM); nonetheless, home-based dietary therapy imposes a substantial parental burden. In this study, we explored differences in parents' health coping behaviors, assessed using the Coping Health Inventory for Parents (CHIP), based on the presence of dietary therapy, child age group, and diagnostic category. A 21-item, CHIP-based questionnaire was distributed via the JaSMIn registry to parents of children with IEM up to school age. Overall, 201 valid responses (56.1% response rate) were analyzed regarding the implementation and perceived usefulness of coping behaviors, stratified by child age, enrollment, diagnosis, and dietary therapy. Parents in the dietary-therapy group reported more coping behaviors than did those in the non-dietary-therapy group. Notably, parents of children aged 1-3 years (not yet in preschool) and those of children with organic acid metabolism disorders rated \"daily home practice of treatments\" as a highly useful coping behavior. Health-related coping behaviors among parents of children with IEM vary substantially according to child age and disease characteristics. Therefore, family support strategies should be tailored to specific developmental stages and treatment requirements.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030405","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}

{"title":"Newborn Critical Congenital Heart Disease Screening Using Pulse Oximetry in a Global Context: Progress, Disparities, and the Importance of Early Detection.","authors":"Lisa A Hom, Gerard R Martin","doi":"10.3390/ijns12020031","DOIUrl":"10.3390/ijns12020031","url":null,"abstract":"<p><p>Congenital heart disease (CHD) remains the number one cause of mortality due to congenital defects in children under the age of one [...].</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030417","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}

{"title":"Pilot Newborn Screening for Vitamin B12 Deficiency in the Czech Republic: Results and Detailed Studies on Identified Babies and Their Mothers.","authors":"Samuel Stanovský, Josef Bártl, Petr Chrastina, Viktor Kožich, Jakub Krijt, Kristýna Nelicová, Jitka Sokolová, Truong An Nguyen, Richard Plavka, Květa Pelinková, Drahomíra Springer, Klára Berková, Zbyněk Straňák, Jan Janota, Katarína Tichá, Jiří Zach, Tomáš Honzík","doi":"10.3390/ijns12020030","DOIUrl":"10.3390/ijns12020030","url":null,"abstract":"<p><p>Neonatal vitamin B12 (B12) deficiency can cause neurodevelopmental harm, and newborn screening (NBS) may enable early detection and treatment. We conducted a multicenter pilot project in four Prague university hospitals between 1 June 2022 and 30 June 2025. Algorithms included the determination of propionylcarnitine-derived primary markers using flow-injection tandem mass spectrometry and second-tier methylmalonic acid (MMA), with total homocysteine measured only when MMA was increased. Of 34,302 screened newborns with consent, 1365 (3.98%) triggered second-tier testing; 9 had MMA > 2.5 µmol/L, of which 8 met the case definition after confirmatory testing, giving a birth frequency of 1:4228 (95% CI 1:2176-1:9931). Positive predictive value was 0.59% (95% CI 0.25-1.15%) and 88.89% (95% CI 51.75-99.72%) for the primary test and second-tier MMA, respectively, with a false positive rate of 0.00292% (95% CI 0.000074-0.01625%). All affected infants were treated orally with cyanocobalamin. Maternal work-up identified confirmed B12 deficiency in four of eight mothers and premalignant gastric changes in two of four positive women. These data support the feasibility, low cost, and clinical utility of incorporating B12 deficiency into Czech NBS, with benefits extending beyond newborn health.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030387","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}

{"title":"Neonatal Screening for CAH in Sweden-Results of Implementing Second-Tier Testing.","authors":"Karin Engström, Rolf H Zetterström, Anna Wedell, Anna Nordenström","doi":"10.3390/ijns12020029","DOIUrl":"10.3390/ijns12020029","url":null,"abstract":"<p><p>Newborn screening for congenital adrenal hyperplasia (CAH) is effective in identifying patients with severe forms before a potentially lethal crisis, but has a relatively high false-positive rate. The aim of this study was to improve the national neonatal screening program in Sweden and the positive predictive value by implementing LC-MS/MS second-tier testing. A combination of two independent parameters, the steroid hormone ratio (androstenedione+17-hydroxyprogesterone)/cortisol and the concentration of 21-deoxycortisol and adjustment of cut-off levels resulted in an increase in the positive predictive value (PPV) from 14% to 84% for full-term infants. In total, the false-positive screening cases decreased by 88%. <i>CYP21A2</i> genotyping was used to determine the severity of CAH in identified cases. We report on the stepwise approach that was used to optimize the cut-off levels for full-term and preterm infants in order not to miss any true cases in the process.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030455","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}