Journal Description
International Journal of Neonatal Screening
International Journal of Neonatal Screening
is an international, peer-reviewed, open access journal on neonatal screening and neonatal medicine published quarterly online by MDPI. The journal is owned by the International Society for Neonatal Screening (ISNS). The International Society for Neonatal Screening (ISNS), German Society for Neonatal Screening (DGNS), the Japanese Society for Neonatal Screening (JSNS), the Association of Public Health Laboratories (APHL) and the UK Newborn Screening Laboratory Network (UKNSLN) are affiliated with IJNS and their members receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, ESCI (Web of Science), PubMed, PMC, Embase, and other databases.
- Journal Rank: JCR - Q1 (Genetics and Heredity) / CiteScore - Q1 (Pediatrics, Perinatology and Child Health)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 28.8 days after submission; acceptance to publication is undertaken in 6.5 days (median values for papers published in this journal in the first half of 2024).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
4.0 (2023);
5-Year Impact Factor:
3.6 (2023)
Latest Articles
Newborn Screening for Sickle Cell Disease in Catalonia between 2015 and 2022—Epidemiology and Impact on Clinical Events
Int. J. Neonatal Screen. 2024, 10(4), 69; https://doi.org/10.3390/ijns10040069 - 3 Oct 2024
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In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence
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In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence of SCD and related hemoglobinopathies in Catalonia and the change in clinical events occurring after introducing NBS. Screening 506,996 newborns from 2015 to 2022, we conducted a retrospective multicenter study including 100 screened (SG) and 95 unscreened (UG) SCD patients and analyzed SCD-related clinical events over the first six years of life. We diagnosed 160 cases of SCD, with an incidence of 1 in 3169 newborns. The SG had a significantly lower median age at diagnosis (0.1 y vs. 1.68 y, p < 0.0001), and initiated penicillin prophylaxis (0.12 y vs. 1.86 y, p < 0.0001) and hydroxyurea treatment earlier (1.42 y vs. 4.5 y, p < 0.0001). The SG experienced fewer median SCD-related clinical events (vaso-occlusive crisis, acute chest syndrome, infections of probable bacterial origin, acute anemia requiring transfusion, acute splenic sequestration, and pathological transcranial Doppler echography) per year of follow-up (0.19 vs. 0.77, p < 0.0001), a reduced number of annual emergency department visits (0.37 vs. 0.76, p < 0.0001), and fewer hospitalizations (0.33 vs. 0.72, p < 0.0001). SCD screening in Catalonia’s NBS program has effectively reduced morbidity and improved affected children’s quality of life.
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Open AccessArticle
Prevalence and Mutation Analysis of Short-Chain acyl-CoA Dehydrogenase Deficiency Detected by Newborn Screening in Hefei, China
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Haili Hu, Qingqing Ma, Weidong Li, Yan Wang, Wangsheng Song and Yong Huang
Int. J. Neonatal Screen. 2024, 10(4), 68; https://doi.org/10.3390/ijns10040068 - 2 Oct 2024
Abstract
Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation with highly variable biochemical and genetic characteristics. The present study aimed to estimate the prevalence and genetic characteristics of SCADD in newborns identified through screening. A total
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Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation with highly variable biochemical and genetic characteristics. The present study aimed to estimate the prevalence and genetic characteristics of SCADD in newborns identified through screening. A total of 782,930 newborns were screened for SCADD in Hefei Neonatal Screening Center from January 2016 to December 2023. The blood samples from newborns were measured by tandem mass spectrometry (MS/MS). The suspected SCADD neonates were rechecked using next-generation gene sequencing for diagnosis. Sanger sequencing was used to verify the mutation site for patients with SCADD and their parents. A total of 21 SCADD cases were confirmed, with an incidence rate of 1/37,282. Genetic mutations were identified in all 21 cases, including 15 cases of compound heterozygous variation and 6 cases of homozygous variation. Twenty-one different mutation types and forty-two mutation sites were discovered, with the most frequent mutation being c.1031A>G, accounting for 21.43% (9/42), followed by c.1130C>T, accounting for 16.67% (7/42). Our findings expand the SCADD mutational spectra. c. 1031A>G and c.1130C>T are the common mutation sites for SCADD genes in newborns. SCADD diagnosed through NBS is primarily a benign condition, and early diagnosis is not necessarily essential.
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Open AccessArticle
A Novel Newborn Screening Program for Sickle Cell Disease in Nigeria
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Aisha A. Galadanci, Umma A. Ibrahim, Yvonne Carroll, Yusuf D. Jobbi, Zubaida L. Farouk, Aisha Mukaddas, Nafiu Hussaini, Bilya Sani Musa, Lauren J. Klein and Michael R. DeBaun
Int. J. Neonatal Screen. 2024, 10(4), 67; https://doi.org/10.3390/ijns10040067 (registering DOI) - 30 Sep 2024
Abstract
Newborn screening for sickle cell disease (SCD) is sparse in sub-Saharan Africa. The leadership of the Aminu Kano Teaching Hospital (AKTH) in Kano, Nigeria, with the support of local religious authorities, established a groundbreaking SCD newborn screening program that has become the standard
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Newborn screening for sickle cell disease (SCD) is sparse in sub-Saharan Africa. The leadership of the Aminu Kano Teaching Hospital (AKTH) in Kano, Nigeria, with the support of local religious authorities, established a groundbreaking SCD newborn screening program that has become the standard of care for pregnant women and their newborns. Our program includes (1) prenatal genetic counseling for all pregnant women in the antenatal clinic, (2) newborn screening, (3) postnatal genetic counseling for parents of newborns diagnosed with SCD and SCT, and (4) referral of newborns with SCD for follow-up in the SCD Comprehensive Care Clinic by 3 months of age. From September 2020 to December 2023, the team screened 7530 infants for SCD at the AKTH, identifying 126 (1.7%) infants with SCD and 1546 (20.5%) with SCT. Of these, 93 (73.8%) newborns with SCD received individualized genetic counseling, and 43 (46%) were referred to the SCD Comprehensive Care Clinic before 3 months. Group genetic counseling was provided to the parents of 778 (50.3%) of newborns identified with SCT. The SCD newborn screening at the AKTH is now standard care, indicating the viability of sustaining an SCD newborn screening program that provides pre- and postnatal genetic counseling and comprehensive SCD care within a low-income setting.
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(This article belongs to the Special Issue A Lifespan Approach to Health and Well-Being Leveraging Neonatal Screening: Efforts in Advocacy, Academia, Research, and Clinical Care)
Open AccessReply
Reply to Bouva et al. Comment on “Dijkstra et al. A False-Negative Newborn Screen for Tyrosinemia Type 1—Need for Re-Evaluation of Newborn Screening with Succinylacetone. Int. J. Neonatal Screen. 2023, 9, 66”
by
Allysa M. Dijkstra, Kimber Evers-van Vliet, M. Rebecca Heiner-Fokkema, Frank A. J. A. Bodewes, Dennis K. Bos, József Zsiros, Koen J. van Aerde, Klaas Koop, Francjan J. van Spronsen and Charlotte M. A. Lubout
Int. J. Neonatal Screen. 2024, 10(4), 66; https://doi.org/10.3390/ijns10040066 (registering DOI) - 24 Sep 2024
Abstract
We thank the authors for their comments [...]
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(This article belongs to the Special Issue Newborn Screening for Disorders of Amino Acid Metabolism)
Open AccessComment
Comment on Dijkstra et al. A False-Negative Newborn Screen for Tyrosinemia Type 1—Need for Re-Evaluation of Newborn Screening with Succinylacetone. Int. J. Neonatal Screen. 2023, 9, 66
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Marelle J. Bouva, Rose E. Maase and Ruurd M. van Elburg
Int. J. Neonatal Screen. 2024, 10(4), 65; https://doi.org/10.3390/ijns10040065 - 24 Sep 2024
Abstract
The assessment of newborn screening (NBS) algorithms’ performance to ensure quality improvements is a continuous process: false-positive referrals can enable optimisations in the shorter term, but false-negative referrals are often only discovered many years after the screening has taken place [...]
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(This article belongs to the Special Issue Newborn Screening for Disorders of Amino Acid Metabolism)
Open AccessArticle
Charting the Ethical Frontier in Newborn Screening Research: Insights from the NBSTRN ELSI Researcher Needs Survey
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Yekaterina Unnikumaran, Mei Lietsch and Amy Brower
Int. J. Neonatal Screen. 2024, 10(3), 64; https://doi.org/10.3390/ijns10030064 - 19 Sep 2024
Abstract
From 2008 to 2024, the Newborn Screening Translational Research Network (NBSTRN), part of the National Institute of Child Health and Human Development (NICHD) Hunter Kelly Newborn Screening Program, served as a robust infrastructure to facilitate groundbreaking research in newborn screening (NBS), public health,
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From 2008 to 2024, the Newborn Screening Translational Research Network (NBSTRN), part of the National Institute of Child Health and Human Development (NICHD) Hunter Kelly Newborn Screening Program, served as a robust infrastructure to facilitate groundbreaking research in newborn screening (NBS), public health, rare disease, and genomics. Over its sixteen years, NBSTRN developed into a significant international network, supporting innovative research on novel technologies to screen, diagnose, treat, manage, and understand the natural history of more than 280 rare diseases. The NBSTRN tools and resources were used by a variety of stakeholders including researchers, clinicians, state NBS programs, parents, families, and policy makers. Resources and expertise for the newborn screening community in ethical, legal, and social issues (ELSI) has been an important area of focus for the NBSTRN and this includes efforts across the NBS system from pilot studies of candidate conditions to public health implementation of screening for new conditions, and the longitudinal follow-up of NBS-identified individuals to inform health outcomes and disease understanding. In 2023, the NBSTRN conducted a survey to explore ELSI issues in NBS research, specifically those encountered by the NBS community. Since NBS research involves collaboration among researchers, state NBS programs, clinicians, and families, the survey was broadly designed and disseminated to engage all key stakeholders. With responses from 88 members of the NBS community, including researchers and state NBS programs, the survey found that individuals rely most on institutional and collegial resources when they encounter ELSI questions. Most survey responses ranked privacy as extremely or very important in NBS research and identified the need for policies that address informed consent in NBS research. The survey results highlight the need for improved collaborative resources and educational programs focused on ELSI for the NBS community. The survey results inform future efforts in ELSI and NBS research in the United States (U.S.) and the rest of the world, including the development of policies and expanded ELSI initiatives and tools that address the needs of all NBS stakeholders.
Full article
(This article belongs to the Special Issue Ethical and Psychosocial Aspects of Genomics in the Neonatal Period)
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Open AccessArticle
Managing Newborn Screening Repeat Collections for Sick and Preterm Neonates
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Ronda F. Greaves, Jo-Ann Northfield, Lauren Cross, Nazha Mawad, Thanh Nguyen, Maggie Tan, Michele A. O’Connell and James Pitt
Int. J. Neonatal Screen. 2024, 10(3), 63; https://doi.org/10.3390/ijns10030063 - 16 Sep 2024
Abstract
Some preterm and sick neonates have altered biochemical profiles and follow-up newborn screening (NBS) collections are recommended. The Victorian NBS program historically recommended repeat collections for babies with birth weight < 1500 g (managed by the maternity service provider) and 3 weeks post-transfusion
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Some preterm and sick neonates have altered biochemical profiles and follow-up newborn screening (NBS) collections are recommended. The Victorian NBS program historically recommended repeat collections for babies with birth weight < 1500 g (managed by the maternity service provider) and 3 weeks post-transfusion (managed by the laboratory). We aimed to determine adherence to current guidelines and review the guidelines to improve NBS performance. To do this, we audited data from 348,584 babies between January 2018 and June 2022. Babies with a recorded birth weight of <1500 g were filtered for inclusion. For the overall review and visualization of the protocol, we sourced information from the literature, our professional society and tertiary hospital services. A total of 2647 babies had a birth weight recorded between 200 and 1499 g. Of these, 2036 (77%) had a second sample collected, indicating that >1 in 5 babies were not receiving a follow-up collection. Our timing of repeat collections for transfused babies, requiring a 3-week follow-up collection, was longer than in other Australasian jurisdictions. A new combined “sick–prem protocol” was launched to support repeat collections and after a 1-year review achieved 95% compliance. We recommend NBS laboratories audit preterm and sick neonate repeat collections to ensure appropriate follow-up. This should be supported with a visual process map to aid education and compliance.
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(This article belongs to the Special Issue Newborn Screening for Congenital Hypothyroidism)
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Open AccessSystematic Review
Wilson and Jungner Revisited: Are Screening Criteria Fit for the 21st Century?
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Elena Schnabel-Besson, Ulrike Mütze, Nicola Dikow, Friederike Hörster, Marina A. Morath, Karla Alex, Heiko Brennenstuhl, Sascha Settegast, Jürgen G. Okun, Christian P. Schaaf, Eva C. Winkler and Stefan Kölker
Int. J. Neonatal Screen. 2024, 10(3), 62; https://doi.org/10.3390/ijns10030062 - 13 Sep 2024
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Driven by technological innovations, newborn screening (NBS) panels have been expanded and the development of genomic NBS pilot programs is rapidly progressing. Decisions on disease selection for NBS are still based on the Wilson and Jungner (WJ) criteria published in 1968. Despite this
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Driven by technological innovations, newborn screening (NBS) panels have been expanded and the development of genomic NBS pilot programs is rapidly progressing. Decisions on disease selection for NBS are still based on the Wilson and Jungner (WJ) criteria published in 1968. Despite this uniform reference, interpretation of the WJ criteria and actual disease selection for NBS programs are highly variable. A systematic literature search [PubMED search “Wilson” AND “Jungner”; last search 16.07.22] was performed to evaluate the applicability of the WJ criteria for current and future NBS programs and the need for adaptation. By at least two reviewers, 105 publications (systematic literature search, N = 77; manual search, N = 28) were screened for relevant content and, finally, 38 publications were evaluated. Limited by the study design of qualitative text analysis, no statistical evaluation was performed, but a structured collection of reported aspects of criticism and proposed improvements was instead collated. This revealed a set of general limitations of the WJ criteria, such as imprecise terminology, lack of measurability and objectivity, missing pediatric focus, and absent guidance on program management. Furthermore, it unraveled specific aspects of criticism on clinical, diagnostic, therapeutic, and economical aspects. A major obstacle was found to be the incompletely understood natural history and phenotypic diversity of rare diseases prior to NBS implementation, resulting in uncertainty about case definition, risk stratification, and indications for treatment. This gap could be closed through the systematic collection and evaluation of real-world evidence on the quality, safety, and (cost-)effectiveness of NBS, as well as the long-term benefits experienced by screened individuals. An integrated NBS public health program that is designed to continuously learn would fulfil these requirements, and a multi-dimensional framework for future NBS programs integrating medical, ethical, legal, and societal perspectives is overdue.
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Open AccessArticle
A Qualitative Study on Engaged Families’ Experiences with Long-Term Follow-Up Care in the Colorado/Wyoming Newborn Screening System
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Stacey Quesada, Lauren Barringer, Marci K. Sontag and Yvonne Kellar-Guenther
Int. J. Neonatal Screen. 2024, 10(3), 61; https://doi.org/10.3390/ijns10030061 - 11 Sep 2024
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Understanding whether the long-term follow-up (LTFU) system is working for families is critical to measuring the success of newborn screening (NBS) and understanding why some families are lost to follow-up. Caregivers were recruited from six pediatric specialty care clinics. Data were gathered from
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Understanding whether the long-term follow-up (LTFU) system is working for families is critical to measuring the success of newborn screening (NBS) and understanding why some families are lost to follow-up. Caregivers were recruited from six pediatric specialty care clinics. Data were gathered from caregivers via five focus groups and one individual interview (n = 24). Caregiver participants represented a wide range of children’s ages and conditions identified through NBS. While this is not the first study to gather caregivers’ input on LTFU, it provides a wide breadth of perspectives (e.g., metabolic, endocrine, hemoglobinopathy, etc.). When asked about goals for their children, caregivers identified health-related goals (i.e., children able to care for themselves, not hindered by diagnosis) and non-health related goals (i.e., defining themselves outside of disease, participating in sports, making friends). In describing the LTFU care they want and need for their child and the key factors that influence access and engagement, caregivers identified three themes: communication and relationships with providers; care team roles and factors; and care access and utilization factors. The themes identified are not disjointed; they are intertwined and illustrate the lived experiences of a sample of families engaged in LTFU care.
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Open AccessArticle
Consistency in the Assessment of Dried Blood Spot Specimen Size and Quality in U.K. Newborn Screening Laboratories
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Stuart J. Moat, James R. Bonham, Christine Cavanagh, Margaret Birch, Caroline Griffith, Lynette Shakespeare, Clare Le Masurier, Claire Manfredonia, Beverly Hird, Philippa Goddard, Sarah Smith, Laura Wainwright, Rachel S. Carling, Jennifer Cundick, Fiona Jenkinson, Catherine Collingwood, Nick Flynn, Nazia Taj, Mehdi Mirzazadeh, Tejswurree Ramgoolam, Liz Robinson, Amy Headley, Tessa Morgan, David Elliman and Lesley Tetlowadd
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Int. J. Neonatal Screen. 2024, 10(3), 60; https://doi.org/10.3390/ijns10030060 - 5 Sep 2024
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In 2015, U.K. newborn screening (NBS) laboratory guidelines were introduced to standardize dried blood spot (DBS) specimen quality acceptance and specify a minimum acceptable DBS diameter of ≥7 mm. The UK ‘acceptable’ avoidable repeat rate (AVRR) is ≤2%. To assess inter-laboratory variability in
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In 2015, U.K. newborn screening (NBS) laboratory guidelines were introduced to standardize dried blood spot (DBS) specimen quality acceptance and specify a minimum acceptable DBS diameter of ≥7 mm. The UK ‘acceptable’ avoidable repeat rate (AVRR) is ≤2%. To assess inter-laboratory variability in specimen acceptance/rejection, two sets of colored scanned images (n = 40/set) of both good and poor-quality DBS specimens were distributed to all 16 U.K. NBS laboratories for evaluation as part of an external quality assurance (EQA) assessment. The mean (range) number of specimens rejected in the first EQA distribution was 7 (1–16) and in the second EQA distribution was 7 (0–16), demonstrating that adherence to the 2015 guidelines was highly variable. A new minimum standard for DBS size of ≥8 mm (to enable a minimum of six sub-punches from two DBS) was discussed. NBS laboratories undertook a prospective audit and demonstrated that using ≥8 mm as the minimum acceptable DBS diameter would increase the AVRR from 2.1% (range 0.55% to 5.5%) to 7.8% (range 0.55% to 22.7%). A significant inverse association between the number of specimens rejected in the DBS EQA distributions and the predicted AVVR (using ≥8 mm minimum standard) was observed (r = −0.734, p = 0.003). Before implementing more stringent standards, the impact of a standard operating procedure (SOP) designed to enable a standardized approach of visual assessment and using the existing ≥7 mm diameter (to enable a minimum of four sub-punches from two DBS) as the minimum standard was assessed in a retrospective audit. Implementation of the SOP and using the ≥7 mm DBS diameter would increase the AVRR from 2.3% (range 0.63% to 5.3%) to 6.5% (range 4.3% to 20.9%). The results demonstrate that there is inconsistency in applying the acceptance/rejection criteria, and that a low AVVR is not an indication of good-quality specimens being received into laboratories. Further work is underway to introduce and maintain standards without increasing the AVRR to unacceptable levels.
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Open AccessArticle
Clinical, Biochemical, and Molecular Characteristics of Filipino Patients with Tyrosinemia Type 1
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Barbra Charina V. Cavan, Leniza G. de Castro-Hamoy, Conchita G. Abarquez, Ebner Bon G. Maceda and Maria Melanie Liberty B. Alcausin
Int. J. Neonatal Screen. 2024, 10(3), 59; https://doi.org/10.3390/ijns10030059 - 31 Aug 2024
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Hereditary tyrosinemia type I (HT1), or hepatorenal tyrosinemia, is an amino acid disorder which may cause hepatic failure as well as renal and neurologic comorbidities. Early detection of this disorder is possible with newborn screening (NBS). The objective of this study is to
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Hereditary tyrosinemia type I (HT1), or hepatorenal tyrosinemia, is an amino acid disorder which may cause hepatic failure as well as renal and neurologic comorbidities. Early detection of this disorder is possible with newborn screening (NBS). The objective of this study is to describe the clinical, biochemical, and molecular characteristics of Filipino patients diagnosed with HT1 through the expansion of the Philippine NBS program in 2014. There were a total of 16 patients with confirmed HT1 from then until September 2022. Clinical and biochemical data during confirmation and initial evaluation, as well as molecular data, were obtained from the patients’ medical records. The cohort included children between the ages of 18 and 54 months at the time of data collection. The mean age at treatment initiation was 26.8 days. The mean succinylacetone level from dried blood spot sampling using tandem mass spectrometry (MS) was 11.1 µmol/L. Biochemical confirmatory tests via plasma amino acid analysis showed mean levels of tyrosine, phenylalanine, and methionine of 506.1 µmol/L, 111.5 µmol/L, and 125.4 µmol/L, respectively. Upon urine organic acid (UOA) analysis, succinylacetone was detected in all except for one patient, who was managed prior to UOA analysis. The most common clinical characteristics were abnormal clotting times (62.5%), elevated alpha fetoprotein (37.5%), anemia (31.3%), and metabolic acidosis (31.3%). The most common genotype was homozygous c.122T>C p.Leu41Pro in 64.3% of patients. The allelic frequency of this pathogenic variant is 71.4%. The inclusion of HT1 in the Philippine NBS program allowed early diagnosis and management of HT1 patients.
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Open AccessArticle
Newborn Screening for Spinal Muscular Atrophy: Variations in Practice and Early Management of Infants with Spinal Muscular Atrophy in the United States
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Craig M. Zaidman, Cameron D. Crockett, Ethan Wedge, Grace Tabatabai and Natalie Goedeker
Int. J. Neonatal Screen. 2024, 10(3), 58; https://doi.org/10.3390/ijns10030058 - 16 Aug 2024
Abstract
In the United States (U.S.), newborn screening (NBS) for spinal muscular atrophy (SMA) is implemented by individual states. There is likely variation in the practice patterns of state NBS programs and among the providers caring for newborns with SMA. This is a prospective,
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In the United States (U.S.), newborn screening (NBS) for spinal muscular atrophy (SMA) is implemented by individual states. There is likely variation in the practice patterns of state NBS programs and among the providers caring for newborns with SMA. This is a prospective, descriptive, observational study that seeks to quantify and describe practice patterns and heterogeneities in state NBS programs and provider practices in the U.S. We surveyed U.S. state NBS programs and care providers of newborns with SMA. Thirty states and 41 practitioners responded. NBS program practices vary by state. Most (74%) state programs provide results to both primary care and specialist providers and also defer confirmatory SMA testing to those providers. Two states had relatively high rates of false-positive or inclusive results. The total birth prevalence of SMA was 1:13,862. Most providers were in tertiary care centers (90%) and were child neurologists (81%) and/or had fellowship training in Neuromuscular Medicine or Electromyography (76%). All providers see new referrals in less than a week, but many do not initiate treatment until >3 weeks of age (39%), with most commonly reported delays related to insurance processes. Most (81%) prefer onasemnogene abeparvovec-xioi (OA) as the treatment of choice, mainly due to perceived efficacy and the route/frequency of administration. NBS practice patterns in the U.S. vary by state but overall yielded the predicted birth prevalence of positive results. Providers evaluate these newborns urgently, but many do not initiate therapy until after 3 weeks of age. Treatment delays are mainly related to insurance processes.
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(This article belongs to the Special Issue Newborn Screening for SMA—State of the Art)
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Open AccessArticle
Our Journey from Individual Efforts to Nationwide Support: Implementing Newborn Screening for Spinal Muscular Atrophy in Serbia
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Miloš Brkušanin, Nemanja Garai, Jelena Karanović, Tamara Šljivančanin Jakovljević, Aleksandra Dimitrijević, Kristina Jovanović, Tanja Lazić Mitrović, Željko Miković, Goran Brajušković, Dimitrije Mihailo Nikolić and Dušanka Savić-Pavićević
Int. J. Neonatal Screen. 2024, 10(3), 57; https://doi.org/10.3390/ijns10030057 - 15 Aug 2024
Abstract
Innovative treatments for spinal muscular atrophy (SMA) yield the utmost advantages only within the presymptomatic phase, underlining the significance of newborn screening (NBS). We aimed to establish statewide NBS for SMA in Serbia. Our stepwise implementation process involved technical validation of a screening
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Innovative treatments for spinal muscular atrophy (SMA) yield the utmost advantages only within the presymptomatic phase, underlining the significance of newborn screening (NBS). We aimed to establish statewide NBS for SMA in Serbia. Our stepwise implementation process involved technical validation of a screening assay, collaboration with patient organizations and medical professionals, a feasibility study, and negotiation with public health representatives. Over 12,000 newborns were tested during the 17-month feasibility study, revealing two unrelated SMA infants and one older sibling. All three children received therapeutic interventions during the presymptomatic phase and have shown no signs of SMA. No false-negative results were found among the negative test results. As frontrunners in this field in Serbia, we established screening and diagnostic algorithms and follow-up protocols and raised awareness among stakeholders about the importance of early disease detection, leading to the incorporation of NBS for SMA into the national program on 15 September 2023. Since then, 54,393 newborns have been tested, identifying six SMA cases and enabling timely treatment. Our study demonstrates that effective collaborations between academia, non-profit organizations, and industry are crucial in bringing innovative healthcare initiatives to fruition, and highlights the potential of NBS to revolutionize healthcare outcomes for presymptomatic SMA infants and their families.
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(This article belongs to the Special Issue Newborn Screening for SMA—State of the Art)
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Open AccessSystematic Review
Systematic Review of Presymptomatic Treatment for Spinal Muscular Atrophy
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Katy Cooper, Gamze Nalbant, Anthea Sutton, Sue Harnan, Praveen Thokala, Jim Chilcott, Alisdair McNeill and Alice Bessey
Int. J. Neonatal Screen. 2024, 10(3), 56; https://doi.org/10.3390/ijns10030056 - 14 Aug 2024
Abstract
Spinal muscular atrophy (SMA) causes the degeneration of motor neurons in the spinal cord. Treatments including nusinersen, risdiplam, and onasemnogene abeparvovec have been shown to be effective in reducing symptoms, with recent studies suggesting greater effectiveness when treatment is initiated in the presymptomatic
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Spinal muscular atrophy (SMA) causes the degeneration of motor neurons in the spinal cord. Treatments including nusinersen, risdiplam, and onasemnogene abeparvovec have been shown to be effective in reducing symptoms, with recent studies suggesting greater effectiveness when treatment is initiated in the presymptomatic stage. This systematic review synthesises findings from prospective studies of presymptomatic treatment for 5q SMA published up to December 2023. The review identified three single-arm interventional studies of presymptomatic treatment (NURTURE, RAINBOWFISH, and SPR1NT), six observational studies comparing presymptomatic or screened cohorts versus symptomatic cohorts, and twelve follow-up studies of screened cohorts only (i.e., babies identified via newborn screening for SMA). Babies with three SMN2 copies met most motor milestones in the NURTURE study of nusinersen and in the SPR1NT study of onasemnogene abeparvovec. Babies with two SMN2 copies in these two studies met most motor milestones but with some delays, and some required ventilatory or feeding support. The RAINBOWFISH study of risdiplam is ongoing. Naïve comparisons of presymptomatic treatment in SPR1NT, versus untreated or symptomatic treatment cohorts, suggested improved outcomes in patients treated presymptomatically. Comparative observational studies supported the finding that presymptomatic treatment, and early treatment following screening, may improve outcomes compared with treatment at the symptomatic stage. Further research should assess the long-term clinical outcomes and cost-effectiveness of presymptomatic treatment for SMA.
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(This article belongs to the Special Issue Newborn Screening for SMA—State of the Art)
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Open AccessArticle
Continuity of Operations in Newborn Screening: Lessons Learned from Three Incidents
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M. Christine Dorley, Elizabeth Bair, Patricia Ryland, Amanda D. Ingram, Emily Reeves, Kara J. Levinson, Ona O. Adair, Jenny F. Meredith and Susanne Crowe
Int. J. Neonatal Screen. 2024, 10(3), 55; https://doi.org/10.3390/ijns10030055 - 1 Aug 2024
Abstract
Three incidents that impacted two US newborn screening (NBS) programs highlight the importance of contingency planning for the continuity of operations (COOP). Other NBS programs may benefit from the experience of these state programs for their own contingency planning efforts. Through after-action reviews
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Three incidents that impacted two US newborn screening (NBS) programs highlight the importance of contingency planning for the continuity of operations (COOP). Other NBS programs may benefit from the experience of these state programs for their own contingency planning efforts. Through after-action reviews conducted post-incident, crucial elements for the successful management of an incident were identified. We detailed the strengths, weaknesses, improvements needed, and future actions that will assist in preparing for other incidents as lessons learned.
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Open AccessArticle
A Five-Year Review of Newborn Screening for Spinal Muscular Atrophy in the State of Utah: Lessons Learned
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Kristen N. Wong, Melissa McIntyre, Sabina Cook, Kim Hart, Amelia Wilson, Sarah Moldt, Andreas Rohrwasser and Russell J. Butterfield
Int. J. Neonatal Screen. 2024, 10(3), 54; https://doi.org/10.3390/ijns10030054 - 22 Jul 2024
Abstract
Spinal muscular atrophy (SMA) is an autosomal recessive condition characterized by alpha motor neuron degeneration in the spinal cord anterior horn. Clinical symptoms manifest in the first weeks to months of life in the most severe cases, resulting in progressive symmetrical weakness and
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Spinal muscular atrophy (SMA) is an autosomal recessive condition characterized by alpha motor neuron degeneration in the spinal cord anterior horn. Clinical symptoms manifest in the first weeks to months of life in the most severe cases, resulting in progressive symmetrical weakness and atrophy of the proximal voluntary muscles. Approximately 95% of SMA patients present with homozygous deletion of the SMN1 gene. With multiple available therapies preventing symptom development and slowing disease progression, newborn screening for SMA is essential to identify at-risk individuals. From 2018 to 2023, a total of 239,844 infants were screened. 13 positive screens were confirmed to have SMA. An additional case was determined to be a false positive. We are not aware of any false-negative cases. All patients were seen promptly, with diagnosis confirmed within 1 week of the initial clinical visit. Patients were treated with nusinersen or onasemnogene abeparvovec. Treated patients with two copies of SMN2 are meeting important developmental milestones inconsistent with the natural history of type 1 SMA. Patients with 3–4 copies of SMN2 follow normal developmental timelines. Newborn screening is an effective tool for the early identification and treatment of patients with SMA. Presymptomatic treatment dramatically shifts the natural history of SMA, with most patients meeting appropriate developmental milestones. Patients with two copies of SMN2 identified through newborn screening constitute a neurogenetic emergency. Due to the complexities of follow-up, a multidisciplinary team, including close communication with the newborn screening program, is required to facilitate timely diagnosis and treatment.
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(This article belongs to the Special Issue Newborn Screening for SMA—State of the Art)
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Open AccessCase Report
Biochemical Pattern of Methylmalonyl-CoA Epimerase Deficiency Identified in Newborn Screening: A Case Report
by
Evelina Maines, Roberto Franceschi, Francesca Rivieri, Giovanni Piccoli, Björn Schulte, Jessica Hoffmann, Andrea Bordugo, Giulia Rodella, Francesca Teofoli, Monica Vincenzi, Massimo Soffiati and Marta Camilot
Int. J. Neonatal Screen. 2024, 10(3), 53; https://doi.org/10.3390/ijns10030053 - 18 Jul 2024
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Methylmalonyl-CoA epimerase enzyme (MCEE) is responsible for catalyzing the isomeric conversion between D- and L-methylmalonyl-CoA, an intermediate along the conversion of propionyl-CoA to succinyl-CoA. A dedicated test for MCEE deficiency is not included in the newborn screening (NBS) panels but it can be
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Methylmalonyl-CoA epimerase enzyme (MCEE) is responsible for catalyzing the isomeric conversion between D- and L-methylmalonyl-CoA, an intermediate along the conversion of propionyl-CoA to succinyl-CoA. A dedicated test for MCEE deficiency is not included in the newborn screening (NBS) panels but it can be incidentally identified when investigating methylmalonic acidemia and propionic acidemia. Here, we report for the first time the biochemical description of a case detected by NBS. The NBS results showed increased levels of propionylcarnitine (C3) and 2-methylcitric acid (MCA), while methylmalonic acid (MMA) and homocysteine (Hcy) were within the reference limits. Confirmatory analyses revealed altered levels of metabolites, including MCA and MMA, suggesting a block in the propionate degradation pathway. The analysis of methylmalonic pathway genes by next-generation sequencing (NGS) allowed the identification of the known homozygous nonsense variation c.139C>T (p.R47X) in exon 2 of the MCE gene. Conclusions: Elevated concentrations of C3 with a slight increase in MCA and normal MMA and Hcy during NBS should prompt the consideration of MCEE deficiency in differential diagnosis. Increased MMA levels may be negligible at NBS as they may reach relevant values beyond the first days of life and thus could be identified only in confirmatory analyses.
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Open AccessArticle
Impact of Lowering TSH Cut-Off on Neonatal Screening for Congenital Hypothyroidism in Minas Gerais, Brazil
by
Nathalia Teixeira Palla Braga, Jáderson Mateus Vilela Antunes, Enrico Antônio Colosimo, Vera Maria Alves Dias, José Nélio Januário and Ivani Novato Silva
Int. J. Neonatal Screen. 2024, 10(3), 52; https://doi.org/10.3390/ijns10030052 - 18 Jul 2024
Abstract
A higher incidence of primary congenital hypothyroidism (CH) has been related to increased sensitivity in neonatal screening tests. The benefit of treatment in mild cases remains a topic of debate. We evaluated the impact of reducing the blood-spot TSH cut-off (b-TSH) from 10
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A higher incidence of primary congenital hypothyroidism (CH) has been related to increased sensitivity in neonatal screening tests. The benefit of treatment in mild cases remains a topic of debate. We evaluated the impact of reducing the blood-spot TSH cut-off (b-TSH) from 10 (Group 2) to 6 mIU/L (Group 1) in a public neonatal screening program. During the study period, 40% of 123 newborns with CH (n = 162,729; incidence = 1:1323) had b-TSH between 6 and 10 mIU/L. Group 1 patients had fewer clinical signs (p = 0.02), lower serum TSH (p < 0.01), and higher free T4 (p < 0.01) compared to those in Group 2 at diagnosis. Reducing the b-TSH cut-off from 10 to 6 mIU/L increased screening sensitivity, allowing a third of diagnoses, mainly mild cases, not being missed. However, when evaluating the performances of b-TSH cut-offs (6, 7, 8, 9, and 10 mIU/L), the lower values were associated with low positive predictive values (PPVs) and unacceptable increased recall rates (0.57%) for a public health care program. A proposed strategy is to adopt a higher b-TSH cut-off in the first sample and a lower one in the subsequent samples from the same child, which yields a greater number of diagnoses with an acceptable PPV.
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(This article belongs to the Special Issue Newborn Screening for Congenital Hypothyroidism)
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CDC’s Laboratory Activities to Support Newborn Screening for Spinal Muscular Atrophy
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Francis K. Lee, Christopher Greene, Kristina Mercer, Jennifer Taylor, Golriz Yazdanpanah, Robert Vogt, Rachel Lee, Carla Cuthbert and Suzanne Cordovado
Int. J. Neonatal Screen. 2024, 10(3), 51; https://doi.org/10.3390/ijns10030051 - 17 Jul 2024
Abstract
Spinal muscular atrophy (SMA) was added to the HHS Secretary’s Recommended Uniform Screening Panel for newborn screening (NBS) in 2018, enabling early diagnosis and treatment of impacted infants to prevent irreversible motor neuron damage. In anticipation of supporting SMA newborn screening, scientists at
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Spinal muscular atrophy (SMA) was added to the HHS Secretary’s Recommended Uniform Screening Panel for newborn screening (NBS) in 2018, enabling early diagnosis and treatment of impacted infants to prevent irreversible motor neuron damage. In anticipation of supporting SMA newborn screening, scientists at the U.S. Centers for Disease Control and Prevention (CDC) have worked towards building resources for public health laboratories in four phases since 2013. In Phase 1, CDC established a real-time PCR assay, which uses a locked nucleic acid probe to attain the needed specificity, to detect SMN1 exon 7. In Phase 2, we developed quality assurance dried blood spot materials made with transduced lymphoblast cell lines established from de-identified SMA patients, carriers, and unaffected donors. In 2021, CDC implemented Phase 3, a proficiency testing program, that now supports 115 NBS labs around the world. We are currently completing Phase 4, which includes the implementation of an external SMA quality control material program. Also, during this time, CDC has provided individual technical assistance to NBS programs and bench training to NBS scientists during our annual molecular workshop. These CDC-led activities have contributed to the rapid and full implementation of SMA screening in all 50 U.S. states as of February 2024.
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(This article belongs to the Special Issue Newborn Screening for SMA—State of the Art)
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One-Year Pilot Study Results of Newborn Screening for Spinal Muscular Atrophy in the Republic of Croatia
by
Darija Šimić, Ana Šarić, Ana Škaričić, Ivan Lehman, Branka Bunoza, Ivana Rako and Ksenija Fumić
Int. J. Neonatal Screen. 2024, 10(3), 50; https://doi.org/10.3390/ijns10030050 - 16 Jul 2024
Abstract
Spinal muscular atrophy (SMA) is a neuromuscular and neurodegenerative disease caused by the homozygous deletion of SMN1 exon 7 in 95% of cases. The prognosis for SMA patients has improved with the development of disease-modifying therapies, all of which are available in Croatia.
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Spinal muscular atrophy (SMA) is a neuromuscular and neurodegenerative disease caused by the homozygous deletion of SMN1 exon 7 in 95% of cases. The prognosis for SMA patients has improved with the development of disease-modifying therapies, all of which are available in Croatia. The best treatment outcomes occur when therapy is applied before symptoms appear, making newborn screening (NBS) for SMA a crucial factor. Since SMA NBS is the first genetic test performed in our laboratory, for successful implementation of the program, we had to overcome logistical and organizational issues. Herein, we present the results of the SMA NBS during the one-year pilot project in Croatia and verify the suitability of the Targeted qPCR™ SMA assay for SMA NBS. The pilot project started on 1 March 2023 in the Department for Laboratory Diagnostics of the University Hospital Center Zagreb. A total of 32,655 newborns were tested. Five SMA patients were detected, and their diagnoses were confirmed by the multiplex ligation-dependent probe amplification (MLPA) assay. There have been no false positive or false negative results, to our knowledge so far. The incidence of SMA determined during the pilot study is consistent with the SMA incidence data from other European countries.
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(This article belongs to the Special Issue Newborn Screening for SMA—State of the Art)
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