International Journal of Neonatal Screening

15 pages, 607 KB

Open AccessArticle

Health Outcomes of Patients with Distal Urea Cycle Disorders Detected by Newborn Screening: Data from the Spanish National Registry

by Raquel Yahyaoui, Pilar Quijada-Fraile, Javier Blasco-Alonso, Inmaculada Vives, David Gil Ortega, Maria-Luz Couce, Paula Sánchez-Pintos, M. Concepción García Jiménez, Silvia Meavilla Olivas, Camila García Volpe, Mariela de los Santos Mercedes, Ángels García-Cazorla, Ana Felipe-Rucián, Lucy Dougherty-de Miguel, Ana Morais López, Ana Bergua Martínez, José David Andrade Guerrero, Sinziana Stanescu, Amaya Belanger, Mercedes Gil-Campos, María José Comino Monroy, Marcello Bellusci, Patricia Pérez-Mohand, Delia Barrio-Carreras, Belén Pérez and Elena Martín-Hernández Show full author list Hide full author list

Int. J. Neonatal Screen. 2026, 12(2), 44; https://doi.org/10.3390/ijns12020044 (registering DOI) - 18 Jun 2026

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Abstract

Urea cycle disorders (UCDs) are rare inherited metabolic diseases associated with toxic hyperammonemia, leading to severe neurological damage and early mortality. Early diagnosis of distal UCDs through newborn screening (NBS) enables presymptomatic intervention; however, comparative real-world outcome data remain limited. We conducted a [...] Read more.

Urea cycle disorders (UCDs) are rare inherited metabolic diseases associated with toxic hyperammonemia, leading to severe neurological damage and early mortality. Early diagnosis of distal UCDs through newborn screening (NBS) enables presymptomatic intervention; however, comparative real-world outcome data remain limited. We conducted a retrospective, multicenter study using data from the Spanish UCD Registry to describe the clinical characteristics and compare health outcomes between patients diagnosed through NBS (n = 40) and those diagnosed after clinical presentation (n = 53). Patients identified by NBS showed a markedly more favorable clinical prognosis, with a mortality rate of 2.5% compared with 15.1% in the unscreened cohort, as well as significantly lower rates of neurological involvement, fewer hospital admissions due to metabolic decompensation, and a reduced need for liver transplantation. Screening also identified a high prevalence of argininosuccinate synthetase deficiency (ASS1D) cases with attenuated biochemical profiles, highlighting the relevance of sensitive screening cutoffs. These findings provide real-world evidence that presymptomatic diagnosis through NBS is associated with improved survival and long-term neurological outcomes in patients with distal UCDs. Full article

5 pages, 169 KB

Open AccessConference Report

Ethical and Clinical Boundaries in Genomics & Newborn Screening: A Brief Report from IPIC2025

by Raquel Yahyaoui, Lúcia Mamede, Martin Zach, James Taylor, Claire Booth, Rosalind Fisher, Věra Franková, Adli Ali, Johan Prevot, Martine Pergent, Roberta Anido de Pena and Elizabeth Rivers

Int. J. Neonatal Screen. 2026, 12(2), 43; https://doi.org/10.3390/ijns12020043 - 18 Jun 2026

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Abstract

The Ethics Session of the International Primary Immunodeficiency Congress (IPIC), held in November 2025 and organised by the International Patient Organisation for Primary Immunodeficiencies (IPOPI), examined one of the most challenging developments emerging from genomic-enhanced newborn screening: the identification of serious, non-treatable disorders [...] Read more.

The Ethics Session of the International Primary Immunodeficiency Congress (IPIC), held in November 2025 and organised by the International Patient Organisation for Primary Immunodeficiencies (IPOPI), examined one of the most challenging developments emerging from genomic-enhanced newborn screening: the identification of serious, non-treatable disorders as incidental detection in programmes originally designed to detect severe combined immunodeficiency (SCID). Using a fictionalised clinical scenario based on the recent literature, the session explored the early diagnosis of ataxia–telangiectasia (AT) detected through TREC-based screening. The discussion highlighted the clinical value and psychological risks associated with presymptomatic detection, the persistent shortcomings in parental consent processes, the systemic pressures created by expanding genomic testing, and the ethical challenges surrounding the reporting and management of incidental findings in screening. The debate underscored the need for internationally coordinated frameworks to guide the management of incidental detection in newborn screening as genomic technologies become more deeply embedded in routine public health practice. Full article

14 pages, 2005 KB

Open AccessArticle

Implementation of a Prospective Birth Cohort for Newborn Screening and Early Linkage to Comprehensive Sickle Cell Disease Care in a Low-Resource Setting

by Umma A. Ibrahim, Aisha B. Musa, Oiza O. Aliu-Isah, Hauwa A. Inuwa, Zubaida L. Farouk, Khadija Bulama, Aisha Mukaddas, Khadija Kamal, Rifkatu N. Auta, Nafiu Hussaini, Aisha A. Galadanci, Yusuf D. Jobbi, Bilya S. Musa, Yvonne Carroll, Lauren J. Klein, Ibrahim M. Idris, Michael R. DeBaun and Muktar H. Aliyu

Int. J. Neonatal Screen. 2026, 12(2), 42; https://doi.org/10.3390/ijns12020042 - 16 Jun 2026

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Abstract

In sub-Saharan Africa, where approximately 75% of newborns with sickle cell disease (SCD) are born, under-five mortality remains high, partly due to the absence of newborn screening (NBS) and delayed linkage to comprehensive care. We conducted a prospective, quasi-experimental study involving two sequential [...] Read more.

In sub-Saharan Africa, where approximately 75% of newborns with sickle cell disease (SCD) are born, under-five mortality remains high, partly due to the absence of newborn screening (NBS) and delayed linkage to comprehensive care. We conducted a prospective, quasi-experimental study involving two sequential newborn screening cohorts at Aminu Kano Teaching Hospital (AKTH), Kano, Nigeria (December 2022–December 2025), to evaluate the feasibility of integrating newborn screening (NBS) with early comprehensive SCD care and to identify barriers to enrollment before 3 months of age. Following an initial implementation period with suboptimal follow-up, a structured family-centered enrollment and communication strategy was introduced to improve early linkage to comprehensive care. During the pre-intervention period, 277 newborns were enrolled (33 with SCD and 244 without SCD [NSCD]), with early enrollment (≤3 months) occurring in 46.5% overall, higher among SCD than NSCD infants (72.8% vs. 43.0%). Delayed enrollment (>6 months) was more frequent among SCD infants. Following the implementation of family-centered communication strategies, 60 additional newborns were enrolled (16 SCD, 44 NSCD), and early enrollment increased to 91.7%. These findings demonstrate that low-cost, family-centered communication and tracking strategies can substantially improve early linkage to comprehensive SCD care following newborn screening in low-resource settings. Early enrollment is a critical step toward reducing morbidity and mortality among children with SCD in low-resource settings. Full article

(This article belongs to the Special Issue Newborn Screening for Sickle Cell Disease Between Point of Care Testing and Next Generation Sequencing – An Impossible Choice or Not?)

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18 pages, 1469 KB

Open AccessArticle

Transitioning from Laboratory-Developed Tests to a Single Commercial Reagent Kit in a National Newborn Screening Program: Impact on Analytical Performance and Harmonization

by Rachel S. Carling, Zoe J. Barclay, Sophie C. Ward, Marie Appleton, Robert Barski, Harry Benn, Kelly Chambers, Paul Coakley, Helena Kemp, Nicola Crabbe, Sarah Dowden, Toby Greenfield, Sarah L. Hogg, Saima Hussein, Rhiannon Marr, Oliver Parkes, Darren Powell, Tejswurree Ramgoolam, Joshua Ssali, Nazia Taj, Katherine Wright, Teresa H. Y. Wu and James R. Bonham Show full author list Hide full author list

Int. J. Neonatal Screen. 2026, 12(2), 41; https://doi.org/10.3390/ijns12020041 - 9 Jun 2026

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Abstract

Newborn screening in England is a national program with laboratories adhering to common screening algorithms. Until recently, screening for inherited metabolic disorders was provided by ten laboratories using laboratory-developed tests (LDTs) and three using commercial assays: harmonization of results proved challenging. Introduction of [...] Read more.

Newborn screening in England is a national program with laboratories adhering to common screening algorithms. Until recently, screening for inherited metabolic disorders was provided by ten laboratories using laboratory-developed tests (LDTs) and three using commercial assays: harmonization of results proved challenging. Introduction of hereditary tyrosinemia type 1 screening meant LDTs required modification to include the measurement of succinylacetone, and subsequent re-validation. This provided an opportunity to implement a single commercial reagent kit in all laboratories. It was anticipated that this would improve analytical performance and harmonization. This study aimed to determine whether these goals were achieved. Verification across the 13 laboratories revealed that the commercial kit reduced inter-laboratory variation for all analytes demonstrating improved harmonization. However, this was achieved by applying instrument-specific correction factors to all analytes, the magnitude of which were significant, indicating a lack of standardization. Performance of succinylacetone was limited by instrument-dependent background interference from the methionine stable isotope label, underscoring the need to establish evidence-based screening cut-off values (COV) rather than adopting published thresholds. This study emphasizes the need for traceable reference materials to improve laboratory quality and the value of screening outcome data. Full article

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9 pages, 830 KB

Open AccessArticle

Development of Dried Blood Spot Proficiency Testing Materials for Newborn Screening of Lysosomal Diseases Using Recombinant Enzymes

by Elya Courtney, Samantha L. Isenberg, Timothy Lim, C. Austin Pickens, Rachel Lee, Carla Cuthbert and Konstantinos Petritis

Int. J. Neonatal Screen. 2026, 12(2), 40; https://doi.org/10.3390/ijns12020040 - 9 Jun 2026

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Abstract

Lysosomal diseases (LDs, or Lysosomal Storage Disorders) have become increasingly visible in the newborn screening community, with the addition of mucopolysaccharidosis type II (MPS-II) into the Recommended Uniform Screening Panel in August 2022 and Infantile Krabbe disease in June 2024. As more LDs [...] Read more.

Lysosomal diseases (LDs, or Lysosomal Storage Disorders) have become increasingly visible in the newborn screening community, with the addition of mucopolysaccharidosis type II (MPS-II) into the Recommended Uniform Screening Panel in August 2022 and Infantile Krabbe disease in June 2024. As more LDs are expected to be considered for screening adoption, the ability to multiplex conditions and expand proficiency testing (PT) using quality control materials is essential. This study examines the use of recombinant enzymes to produce first-tier PT materials for mucopolysaccharidosis type I, MPS-II, Gaucher, Fabry, Krabbe, Pompe, and Niemann–Pick A/B (acid sphingomyelinase deficiency)—adding four disorders to the CDC’s Newborn Screening Quality Assurance Program (NSQAP) LD PT panel. Through an iterative process that included two prototype phases, two pilot phases, and external testing by up to 31 external laboratories, a new manufacturing process was developed for producing high-performing dried blood spot-based LD PT specimens. Materials were evaluated using several methods commonly employed by newborn screening laboratories, including tandem mass spectrometry with flow injection and liquid chromatography, digital microfluidics, and fluorometric assays. This novel process for producing LD PT materials offers several advantages over previous manufacturing methods that relied on immortalized cell lines from affected patients. Improved scalability, for example, has enabled NSQAP to expand LD PT enrollment internationally. Furthermore, the new process makes it easier to support future expansions of the LD screening panel. The updated specimens and expanded program were launched in January 2025. Full article

(This article belongs to the Special Issue Advances in Newborn Screening for Lysosomal Disorders: From Laboratory Screening to Diagnosis)

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11 pages, 1386 KB

Open AccessArticle

A Four-Year Prospective Pilot Study of Newborn Screening for Late-Onset Proximal Urea-Cycle Disorders in Hyogo Prefecture in Japan

by Tomoko Lee, Miki Matsui, Yoko Yokoyama, Ryosuke Bo, Hiroyuki Awano, Dai Kataoka, Masaaki Ueda, Toshinori Minato, Hironori Kobayashi, Yuki Hasegawa, Kei Murayama and Yasuhiro Takeshima

Int. J. Neonatal Screen. 2026, 12(2), 39; https://doi.org/10.3390/ijns12020039 - 4 Jun 2026

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Abstract

Proximal urea-cycle disorders (PUCDs), including N-acetylglutamate synthase deficiency (NAGSD), ornithine transcarbamylase deficiency (OTCD), and carbamoyl phosphate synthase 1 deficiency (CPS1D), cause hyperammonemia and impair neurological outcomes. Early detection of late-onset forms allows presymptomatic intervention to prevent hyperammonemia; however, reliable newborn screening (NBS) markers [...] Read more.

Proximal urea-cycle disorders (PUCDs), including N-acetylglutamate synthase deficiency (NAGSD), ornithine transcarbamylase deficiency (OTCD), and carbamoyl phosphate synthase 1 deficiency (CPS1D), cause hyperammonemia and impair neurological outcomes. Early detection of late-onset forms allows presymptomatic intervention to prevent hyperammonemia; however, reliable newborn screening (NBS) markers are lacking. This prospective pilot study in Hyogo Prefecture, Japan, evaluated hypocitrullinemia as a screening marker for late-onset PUCDs. Newborns with citrulline levels below the 0.05th percentile on NBS between June 2020 and May 2024 were enrolled in the study. Confirmatory diagnosis of PUCDs was performed using plasma amino acids, urinary organic acids, and genetic testing. During the first period (101,172 newborns), 11 newborns exhibited hypocitrullinemia; 10 underwent further evaluation. One newborn was diagnosed with CPS1D (compound heterozygous CPS1 variants); another was later diagnosed with Leigh syndrome. The remaining eight cases were false positives, often associated with prematurity, poor feeding, or gastrointestinal disorders. A second dried blood spot (DBS) card protocol was introduced in the second period (34,694 newborns), reducing false positives. One neonatal-onset OTCD case was detected, and citrulline levels were normalized in six of the seven other cases. In summary, hypocitrullinemia can identify presymptomatic PUCDs, and requesting a second DBS card reduces false positives, supporting its feasibility for incorporation into NBS programs. Full article

(This article belongs to the Collection Newborn Screening in Japan)

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18 pages, 2000 KB

Open AccessArticle

Newborn Screening for Spinal Muscular Atrophy in the Republic of Moldova: A Feasibility Study and First Steps

by Iulia Coliban, Natalia Usurelu, Igor Opalco, Sergiu Gladun and Victoria Sacara

Int. J. Neonatal Screen. 2026, 12(2), 38; https://doi.org/10.3390/ijns12020038 - 28 May 2026

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Abstract

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, [...] Read more.

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; SMN1 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. Full article

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14 pages, 423 KB

Open AccessArticle

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

by Aihua Xia, Hongfei Chen, Fuhua Lu, Ping Xu, Peixiao Shen, Wei Wei, Chunrong Gui, Juliang Liu, Dan Wei, Haipeng Qin, Yan Huang, Ju Long and Baoheng Gui

Int. J. Neonatal Screen. 2026, 12(2), 37; https://doi.org/10.3390/ijns12020037 - 22 May 2026

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Abstract

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 [...] Read more.

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. Full article

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10 pages, 1071 KB

Open AccessArticle

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

by Go Tajima, Nobuyuki Ishige, Junji Hanai and Keiko Konomura

Int. J. Neonatal Screen. 2026, 12(2), 36; https://doi.org/10.3390/ijns12020036 - 15 May 2026

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Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Collection Newborn Screening in Japan)

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14 pages, 686 KB

Open AccessReview

Newborn Screening in Saudi Arabia: Brief History, Current Practice, and Future Direction

by Ahmed H. Mujamammi

Int. J. Neonatal Screen. 2026, 12(2), 35; https://doi.org/10.3390/ijns12020035 - 13 May 2026

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Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Newborn Screening Developing Programs in Asia)

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19 pages, 264 KB

Open AccessArticle

Parents’ Experiences of Receiving a Severe Combined Immunodeficiency (SCID) or Non-SCID T-Cell Lymphopenia Outcome During the Newborn Screening Evaluation in England

by Pru Holder, Chloe Musa, Jim B. Chilcott, Anju D. Keetharuth, Louise Moody, Ellinor K. Olander, Fiona Ulph and Jane Chudleigh

Int. J. Neonatal Screen. 2026, 12(2), 34; https://doi.org/10.3390/ijns12020034 - 12 May 2026

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Abstract

Background: 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 [...] Read more.

Background: 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. Methods: A qualitative exploratory design was employed using semi-structured interviews with 12 parents (n = 5 who had received an SCID outcome and n = 7 who had received a non-SCID TCL following SCID NBS). Results: 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. Conclusions: 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. Full article

10 pages, 353 KB

Open AccessArticle

Conjugated Hyperbilirubinemia in Early Infancy: Rethinking Diagnostic Cut-Offs—A Retrospective Analysis

by Daniel Pfurtscheller, Carola Ganzer, Ena Suppan, Melina Winkler, Bernhard Schwaberger, Lisa Sallmon, Gerhard Pichler and Benno Kohlmaier

Int. J. Neonatal Screen. 2026, 12(2), 33; https://doi.org/10.3390/ijns12020033 - 11 May 2026

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Abstract

Background: 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 [...] Read more.

Background: 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. Methods: 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. Results: 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; p < 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. Conclusions: 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. Full article

(This article belongs to the Special Issue Newborn Screening for Physical/Structural Birth Defects)

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19 pages, 282 KB

Open AccessArticle

by Yuko Matsumoto, Yuko Kushihashi, Akiko Suwa and Go Tajima

Int. J. Neonatal Screen. 2026, 12(2), 32; https://doi.org/10.3390/ijns12020032 - 6 May 2026

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Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Collection Newborn Screening in Japan)

6 pages, 465 KB

Open AccessEditorial

Newborn Critical Congenital Heart Disease Screening Using Pulse Oximetry in a Global Context: Progress, Disparities, and the Importance of Early Detection

by Lisa A. Hom and Gerard R. Martin

Int. J. Neonatal Screen. 2026, 12(2), 31; https://doi.org/10.3390/ijns12020031 - 5 May 2026

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Abstract

Congenital heart disease (CHD) remains the number one cause of mortality due to congenital defects in children under the age of one [...] Full article

(This article belongs to the Special Issue Global Updates on the Advancements in CCHD Screening)

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15 pages, 883 KB

Open AccessArticle

Pilot Newborn Screening for Vitamin B12 Deficiency in the Czech Republic: Results and Detailed Studies on Identified Babies and Their Mothers

by 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 and Tomáš Honzík

Int. J. Neonatal Screen. 2026, 12(2), 30; https://doi.org/10.3390/ijns12020030 - 5 May 2026

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Abstract

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 [...] Read more.

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. Full article

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13 pages, 2874 KB

Open AccessArticle

Neonatal Screening for CAH in Sweden—Results of Implementing Second-Tier Testing

by Karin Engström, Rolf H. Zetterström, Anna Wedell and Anna Nordenström

Int. J. Neonatal Screen. 2026, 12(2), 29; https://doi.org/10.3390/ijns12020029 - 1 May 2026

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Abstract

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 [...] Read more.

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%. CYP21A2 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. Full article

(This article belongs to the Special Issue The Impact of Second-Tier Tests on Newborn Screening Performance: Benefits and Challenges)

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10 pages, 1345 KB

Open AccessArticle

The Variation in IRT in Different Ethnic Groups in England—Implications for a Newborn Screening Programme for CF in Diverse Multiethnic Populations

by Toby Greenfield, Lesley Tetlow, James R. Bonham, Catherine Collingwood, Laura Wainwright, Liz Robinson, Dave Wright, Beverly Hird, Tejswurree Ramgoolam, Caroline Griffith, Lynette Shakespeare, Mehdi Mirzazadeh, Rachelle Garstone, Deborah Finnerty, Nick Flynn, Nazia Taj and Maya Desai

Int. J. Neonatal Screen. 2026, 12(2), 28; https://doi.org/10.3390/ijns12020028 - 28 Apr 2026

Viewed by 540

Abstract

Increasing ethnic diversity raises potential inequalities within screening programmes. In the UK, newborns are screened for CF by initially measuring IRT. Dried blood spot IRT levels above a set cut-off require follow-up testing to establish a screening result. Variation exists in IRT levels [...] Read more.

Increasing ethnic diversity raises potential inequalities within screening programmes. In the UK, newborns are screened for CF by initially measuring IRT. Dried blood spot IRT levels above a set cut-off require follow-up testing to establish a screening result. Variation exists in IRT levels between different ethnicities and therefore impacts the number of potentially false positive results obtained from ethnic groups. Over a 4-year period, IRT data was collected, and the 99.5th centile was calculated for different ethnic groups. Significant differences were noticed between ethnic groups, and the CF outcome data over a 10-year period were then analysed to establish the effect this had on positive predictive values. The largest difference in IRT 99.5th centile values was seen between the White British and Black African groups. Positive predictive values for Black African and Indian ethnic groups were much lower than the other groups. Rather than try to incorporate ethnicity into the UK CF screening algorithm, we suggest making CF clinicians aware of the differences between different ethnic groups to inform counselling families who receive screen-positive results. Full article

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11 pages, 489 KB

Open AccessArticle

21-Deoxycortisone: A Novel Sensitive and Specific Newborn Screening Marker for Congenital Adrenal Hyperplasia

by Mark de Hora, Natasha Heather, Dianne Webster, Benjamin B. Albert and Paul Hofman

Int. J. Neonatal Screen. 2026, 12(2), 27; https://doi.org/10.3390/ijns12020027 - 27 Apr 2026

Viewed by 603

Abstract

21-deoxycortisol is a sensitive and specific blood marker for congenital adrenal hyperplasia (CAH). We postulated that 21-deoxycortisone, the 11β-hydroxysteroid dehydrogenase metabolite of 21-deoxycortisol, may also be an accurate bloodspot marker of CAH. Measurement of 21-deoxycortisone was performed on 42 residual NBS specimens with [...] Read more.

21-deoxycortisol is a sensitive and specific blood marker for congenital adrenal hyperplasia (CAH). We postulated that 21-deoxycortisone, the 11β-hydroxysteroid dehydrogenase metabolite of 21-deoxycortisol, may also be an accurate bloodspot marker of CAH. Measurement of 21-deoxycortisone was performed on 42 residual NBS specimens with a true positive result for CAH, 11 with a false negative result, and 439 specimens with a false positive result. For this study, the test was considered positive if 21-deoxycortisone was detected. The sensitivity and specificity of 21-deoxycortisone as a marker for classical CAH was calculated and compared to 21-deoxycortisol data from a previous New Zealand study. The method for 21-deoxycortisone measurement was linear to 1000 nmol/L and precision was 7.3–10.3%. The lower limit of quantification was 2 nmol/L, and recovery was 99%. 21-deoxycortisone was ≥2 nmol/L in all 42 true positive samples and in 10 false negative samples, and was not detected in the false positive group of specimens. The sensitivity of 21-deoxycortisone was 98.1%, and specificity was 100%. In a previous study, the sensitivity of 21-deoxycortisol was 88.7% and specificity was 99.8% in 1910 newborn screening tests carried out between 2018 and 2021. Incorporating 21-deoxycortisone into a second-tier test and adjustment of primary screening protocols could improve the accuracy of newborn screening for CAH. Longer term prospective studies on the performance of 21-deoxycortisone are warranted. Full article

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18 pages, 282 KB

Open AccessArticle

Parental Views on the Psychosocial Impact of False-Positive Results Following Newborn Screening for Severe Combined Immunodeficiency in England

by Pru Holder, Chloe Musa, Anju Keetharuth, Fiona Ulph, Jim B. Chilcott, Louise Moody, Ellinor K. Olander and Jane Chudleigh

Int. J. Neonatal Screen. 2026, 12(2), 26; https://doi.org/10.3390/ijns12020026 - 21 Apr 2026

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Abstract

The project aimed to explore the psychosocial impact on parents of receiving a false-positive outcome following a positive newborn bloodspot screening (NBS) result for SCID for their child. A mixed-methods design was employed using semi-structured interviews and standardised health-related questionnaires (EQ-5D-5L, ITQOL-47, and [...] Read more.

The project aimed to explore the psychosocial impact on parents of receiving a false-positive outcome following a positive newborn bloodspot screening (NBS) result for SCID for their child. A mixed-methods design was employed using semi-structured interviews and standardised health-related questionnaires (EQ-5D-5L, ITQOL-47, and GAD-7). The participants were recruited from six National Health Service hospital trusts in England involved in the NHS England In-Service Evaluation of Screening for SCID. A total of 22 interviews were conducted with 28 parents. Health-related questionnaire data were collected from 26 of these parents. The interviews were analysed using a reflexive deductive approach to thematic analysis. For the health-related questionnaire data, a comparison of group means against population norms was undertaken using t-tests with unequal variances. The findings from the interviews showed that receiving a false-positive outcome following a positive NBS SCID result could cause parents to have an enhanced view of their child’s vulnerability in the short term. However, negative sequelae were largely mitigated as parents viewed their child’s exposure to ‘normal’ infections as evidence of a functional immune system. The health-related questionnaire data showed that the parents had significantly worse health than the population norm (as indicated by EQ-VAS: p = 0.0296); however, all the other measures were non-significant. More research is needed to explore the potential longer-term psychosocial impact of a false-positive screening result for SCID on parents beyond their child’s first year of life. Full article

10 pages, 1048 KB

Open AccessArticle

COASY-Associated Disorders as a Differential Diagnosis in Cases with Newborn Screening Results Suggestive of CPT-I

by Zinandré Stander, Amy L. White, Matthew Lynch, David Coman, Justin Rosati, Diana Bailey, Jessica Johnson, Bo Hoon Lee, ChinTo Fong, Joseph Orsini, Matthew J. Schultz, Devin Oglesbee, Dimitar Gavrilov, Dietrich Matern, Patricia L. Hall and Silvia Tortorelli

Int. J. Neonatal Screen. 2026, 12(2), 25; https://doi.org/10.3390/ijns12020025 - 17 Apr 2026

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Abstract

COASY-related disorders (CRDs) are a spectrum of autosomal recessive conditions caused by the dysfunction of CoA synthase, an enzyme responsible for the final steps of CoA synthesis. Clinical manifestations of CRDs are highly variable, ranging from perinatal lethal pontocerebellar hypoplasia to childhood-onset [...] Read more.

COASY-related disorders (CRDs) are a spectrum of autosomal recessive conditions caused by the dysfunction of CoA synthase, an enzyme responsible for the final steps of CoA synthesis. Clinical manifestations of CRDs are highly variable, ranging from perinatal lethal pontocerebellar hypoplasia to childhood-onset neurodegenerative brain iron accumulation, which is often recognized after clinical regression. Recent reports have described a few individuals with CRD who screened positive for carnitine palmitoyltransferase-I deficiency by newborn screening (NBS). However, heterogeneous clinical presentations, conflicting biochemical/molecular sequencing of CPT1A, and a lack of metabolic characterization have led to lengthy, costly diagnostic journeys. To address some of these aspects, this investigation retrospectively evaluated NBS acylcarnitine patterns in five CRD cases using Collaborative Laboratory Integrated Reports (CLIR). A total of 25 metabolites/ratios were identified to deviate significantly from reference ranges and were primarily composed of elevated free carnitine and reduced long-chain acylcarnitine levels. While low acylcarnitine concentrations are often not reported due to a lack of lower reference cutoffs, ratios involving these metabolites relative to short-chain acylcarnitines could aid in identifying CRD cases via NBS. When comparing this pattern to CPT-Ia cases, we confirmed a nearly identical acylcarnitine pattern between these, and thus support the need to consider CRD in cases with NBS results suggestive of CPT-Ia. This study is the first case series to characterize NBS patterns in patients with CRD and highlights the unique opportunity for early detection, particularly in cases that are neonatally asymptomatic and have unremarkable confirmatory biochemical results. Full article

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13 pages, 556 KB

Open AccessArticle

Evaluation of Implementation of Newborn Screening for Sickle Cell Disease Program in Selected Hospitals in Dar es Salaam, Tanzania

by Tunganege Matipa, Elia Nyangi, Agnes Jonathan, Mwashungi Ally, Lulu Chirande, Asteria Mpoto, Emmanuel Balandya and Gladys Reuben Mahiti

Int. J. Neonatal Screen. 2026, 12(2), 24; https://doi.org/10.3390/ijns12020024 - 15 Apr 2026

Viewed by 908

Abstract

Sickle cell disease (SCD) is a major public health concern in Tanzania where approximately 11,000 children are born with the condition annually. Newborn screening (NBS) enables early diagnosis and timely intervention. Despite the proven effectiveness of NBS in reducing early mortality from SCD, [...] Read more.

Sickle cell disease (SCD) is a major public health concern in Tanzania where approximately 11,000 children are born with the condition annually. Newborn screening (NBS) enables early diagnosis and timely intervention. Despite the proven effectiveness of NBS in reducing early mortality from SCD, implementation in Tanzania remains limited to pilot programs at facilities such as Temeke and Amana Regional Referral Hospitals (RRHs) in the city of Dar-es-salaam. This study evaluated the implementation of NBS for the SCD Program at Temeke and Amana RRHs. An explanatory mixed-methods process evaluation was conducted between January 2022 and December 2024. Quantitative data were extracted from hospital registries and REDCap, while qualitative data were obtained from key informant interviews with 17 healthcare workers. Quantitative data were analyzed using SPSS v29.0, while qualitative transcripts were thematically analyzed using NVivo software version 15 to explore operational factors influencing implementation. A total of 10,711 newborns were screened across the two hospitals. Seventy-four (0.70%) newborns had homozygous SCD (HbS/S), whereas 1325 (12.53%) had sickle cell trait (HbA/S). Enrolment of infants diagnosed with SCD into comprehensive care declined substantially over time, from 65.6% in 2022 to 10.5% in 2024 at Temeke RRH, while Amana RRH recorded no enrolments beyond the first year of implementation. Qualitative findings highlighted facilitators for NBS such as maternal awareness, interdepartmental collaboration, and the availability of trained staff. However, implementation was hindered by inadequate refresher training, delayed staff incentives, supply shortages, and parental hesitancy influenced by cultural beliefs. This evaluation found a substantial decline in enrolment of newborns diagnosed with SCD into comprehensive care, driven by key operational challenges. Although early implementation benefited from trained, committed staff and interdepartmental collaboration, sustainability was limited by inadequate refresher training, delayed incentives, supply shortages, and parental hesitancy. Addressing these gaps through regular capacity building, strengthened supply chains, timely incentives, and culturally sensitive community education is critical to improving enrolment, continuity of care, and informing national scale-up of NBS for SCD in Tanzania. Full article

(This article belongs to the Special Issue Newborn Screening for Sickle Cell Disease Between Point of Care Testing and Next Generation Sequencing – An Impossible Choice or Not?)

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12 pages, 942 KB

Open AccessTechnical Note

A Systematic Process to Accurately Link Large-Scale Research Consents to State Public Health Newborn Screening Samples

by Emily Cheves, Hannah E. Frawley, Angela You Gwaltney, Ana N. Forsythe, Samantha Scott, John Colin Mathews, Jake Dibble, Tanya Reeve, Vesselina Bakalov, Manisha Dass, Heidi L. Cope, Curt Scharfe and Holly Peay

Int. J. Neonatal Screen. 2026, 12(2), 23; https://doi.org/10.3390/ijns12020023 - 14 Apr 2026

Viewed by 615

Abstract

Research programs can interface with public health programs to generate innovation, yet it is critical to ensure processes that support research activities without infringing on protected data. Genomic newborn screening (gNBS) research programs require reliable methods to link parental consents to the correct [...] Read more.

Research programs can interface with public health programs to generate innovation, yet it is critical to ensure processes that support research activities without infringing on protected data. Genomic newborn screening (gNBS) research programs require reliable methods to link parental consents to the correct newborn screening (NBS) specimen. Early Check is a gNBS research program in North Carolina that uses the residual dried bloodspot (DBS) samples stored at the North Carolina State Laboratory of Public Health (NCSLPH) to screen babies for serious health conditions. Early Check created a systematic approach to match research consents with NBS DBS samples utilizing a fuzzy matching algorithm and manual review of prospective matches utilizing a decision tree. Between 28 September 2023, and 10 June 2025, Early Check received parental consents for 4279 newborns. Of those, 614 (14%) had discrepancies that required further review. More than half of these (349, 57%) required outreach to the consenting parent to resolve differences in information such as name, infant sex, or contact details. The use of probabilistic matching, a decision tree, and structured staff review provides a feasible approach for accurately identifying samples from consented NBS participants. Full article

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15 pages, 1440 KB

Open AccessArticle

Acid Sphingomyelinase Activity in Dried Blood Spot from Neonatal Intensive Care Unit–Admitted Neonates: A Pilot Study for Expanded Newborn Screening in Japan

by Akie Kato, Atsuko Noguchi, Hiroyuki Adachi, Kiichi Takahashi, Masato Ito, Tomoo Ito, Shozo Ota and Hirokazu Arai

Int. J. Neonatal Screen. 2026, 12(2), 22; https://doi.org/10.3390/ijns12020022 - 1 Apr 2026

Viewed by 799

Abstract

Acid sphingomyelinase deficiency (ASMD) is currently treatable with olipudase alfa, increasing the need for early newborn screening (NBS). We conducted a two-center pilot cohort study to characterize dried blood spot (DBS) acid sphingomyelinase (ASM) activity in Japanese neonates in the neonatal intensive care [...] Read more.

Acid sphingomyelinase deficiency (ASMD) is currently treatable with olipudase alfa, increasing the need for early newborn screening (NBS). We conducted a two-center pilot cohort study to characterize dried blood spot (DBS) acid sphingomyelinase (ASM) activity in Japanese neonates in the neonatal intensive care unit (NICU). ASM activity was measured by flow injection-tandem mass spectrometry in 244 NICU-admitted neonates (gestational age 25–41 weeks; birth weight 773–4201 g); longitudinal paired samples were available in 34 neonates with birth weight < 2000 g and concurrent hematology in 43 neonates. The mean ASM activity was 3.7 ± 1.2 μmol/h/L (95% confidence interval, 3.54–3.84; range, 1.7–11.6), with a right-skewed distribution. ASM activity correlated positively with birth weight (r = 0.184, p = 0.0039), gestational age (r = 0.219, p = 0.0006), and lymphocyte count (ρ = 0.394, p = 0.0089) and negatively with hematocrit (ρ = −0.372, p = 0.014). In neonates with a birth weight < 2000 g, ASM increased significantly on repeat sampling (mean difference, 1.60 μmol/h/L; p < 0.0001; Cohen’s d = 0.912). These findings support NICU-specific reference ranges, hematology-informed interpretations, repeat testing after maturation, and the use of second-tier biomarkers for ASMD NBS implementation in Japan. Full article

(This article belongs to the Collection Newborn Screening in Japan)

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11 pages, 604 KB

Open AccessArticle

Cost-Effectiveness of Newborn Screening for Infantile-Onset Pompe Disease in Japan

by Keiko Konomura, Motoko Tanaka, Go Tajima and Eri Hoshino

Int. J. Neonatal Screen. 2026, 12(2), 21; https://doi.org/10.3390/ijns12020021 - 31 Mar 2026

Cited by 1 | Viewed by 1030

Abstract

We conducted a cost-effectiveness analysis of a universal newborn screening (NBS) program for infantile-onset Pompe disease (IOPD) compared with clinical identification in newborns. The analytical model combined a decision tree and a Markov model. The incremental cost-effectiveness ratio (ICER) was estimated over a [...] Read more.

We conducted a cost-effectiveness analysis of a universal newborn screening (NBS) program for infantile-onset Pompe disease (IOPD) compared with clinical identification in newborns. The analytical model combined a decision tree and a Markov model. The incremental cost-effectiveness ratio (ICER) was estimated over a lifetime horizon, applying a 2% annual discount rate from the public healthcare payer’s perspective. In a cohort of 727,288 individuals, 2.4 patients were expected to have IOPD. The cumulative quality-adjusted life years (QALYs) gained per patient were estimated to be 7.9 when clinically diagnosed and treated with enzyme replacement therapy, and 28.9 when identified through universal NBS. The ICER was 174 million JPY per QALY. Sensitivity and scenario analyses indicated that the parameters most affecting the ICER were the NBS test cost, the quality-of-life value for ambulatory patients, the prevalence of IOPD, and the cost of enzyme replacement therapy. Although considerable uncertainty exists in the analysis, the findings suggest that implementing NBS solely for detecting infantile-onset cases poses challenges in terms of cost-effectiveness, primarily due to the rarity of the disease and the high costs associated with testing and treatment. Full article

(This article belongs to the Collection Newborn Screening in Japan)

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9 pages, 211 KB

Open AccessArticle

A Survey of Current Australasian Practices in the Use of Residual Bloodspots for the Addition of a New Disorder to the Screening Panel

by Lawrence Greed, James Pitt, Ronda F. Greaves, Kate Coleman, Gabrielle Crisp, Enzo Ranieri, Mark de Hora, Dianne Webster and Natasha Heather

Int. J. Neonatal Screen. 2026, 12(2), 20; https://doi.org/10.3390/ijns12020020 - 30 Mar 2026

Viewed by 694

Abstract

Newborn screening (NBS) bloodspots are primarily used to test for a defined panel of conditions, yet screening expansion has necessitated the implementation of new tests. Integral to test implementation across all clinical laboratories is the need to evaluate the method with clinical samples, [...] Read more.

Newborn screening (NBS) bloodspots are primarily used to test for a defined panel of conditions, yet screening expansion has necessitated the implementation of new tests. Integral to test implementation across all clinical laboratories is the need to evaluate the method with clinical samples, and a common secondary use of residual bloodspots, which are samples that remain following conventional screening, is validating new testing methods by establishing “normal” analyte concentrations and setting action decision limits for NBS protocols prior to implementation. Analysis of de-identified residual bloodspots may potentially reveal an infant with a treatable condition, and re-identification and clinical notification of the infant may then be prudent. However, consent to test residual samples for conditions under implementation may not have been obtained. This ethical dilemma risks the inclusion of residual bloodspots in test development being declined by over-arching NBS authorities. Consequently, the Human Genetics Society of Australasia (HGSA) NBS Committee issued a survey to the Australasian NBS laboratories regarding the current practices of the use of residual bloodspots for new test implementation. The questionnaire revealed a consistent requirement for residual NBS bloodspot analysis to determine reference ranges and screening cutoffs for biochemical variants. If using de-identified residual samples as a component of test validation, re-identification of infants with out-of-range results for clinical referral was considered ethically justified for potentially treatable conditions. The survey results will be used to develop a consensus approach in the region that is both ethically and scientifically valid. Full article

15 pages, 1156 KB

Open AccessArticle

A Multi-Stakeholder Perspective on Integrating Genomic Sequencing into Newborn Screening: An Interview Study

by Saskia G. Smits, Suzanne M. Onstwedder, Tessel Rigter, Wendy Rodenburg and Lidewij Henneman

Int. J. Neonatal Screen. 2026, 12(2), 19; https://doi.org/10.3390/ijns12020019 - 26 Mar 2026

Viewed by 854

Abstract

Interest in the genomic sequencing of healthy newborns has raised a discussion on whether this technology should be introduced into existing newborn screening (NBS) programs. This qualitative study explores a multi-stakeholder perspective on the future of genomic sequencing in NBS. Semi-structured interviews were [...] Read more.

Interest in the genomic sequencing of healthy newborns has raised a discussion on whether this technology should be introduced into existing newborn screening (NBS) programs. This qualitative study explores a multi-stakeholder perspective on the future of genomic sequencing in NBS. Semi-structured interviews were conducted with 26 professionals involved in NBS or in clinical genome sequencing in the Netherlands. Participants highlighted opportunities such as the possibility to use one test for a wide range of genetic conditions, reducing diagnostic odyssey, expanding the scope of NBS, and increasing program efficiency. Challenges were raised regarding genetic variant interpretation, expected increased parental anxiety, data privacy issues, difficulties with information provision, and high costs. Three areas of tension between participants’ perspectives were identified: screening strategy, screening performance, and roles and responsibilities. It was emphasized that implementing genomic sequencing should not risk reducing the current high NBS participation, and that enhancing knowledge, communication, and collaboration between all stakeholders is needed. Although most participants did not believe genomic sequencing as a first-tier test is currently desirable and feasible, they acknowledged it has a role to play in the future of NBS. Future decision-making should consider the potential impact on the participation rate, program quality, and balancing benefits and harms. Full article

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Int. J. Neonatal Screen., Volume 12, Issue 2 (June 2026) – 26 articles

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