International Journal of Neonatal Screening

13 pages, 2448 KiB

Open AccessArticle

Analysis of the Effect of Demographic Variables on Lysosomal Enzyme Activities in the Missouri Newborn Screening Program

by Lacey Vermette, Jon Washburn and Tracy Klug

Int. J. Neonatal Screen. 2025, 11(2), 48; https://doi.org/10.3390/ijns11020048 - 19 Jun 2025

Abstract

Newborn screening laboratories are increasingly adding lysosomal storage disorders (LSDs), such as Mucopolysaccharidosis I (MPS I) and Pompe disease, to their screening panels. Without newborn screening, LSDs are frequently diagnosed only after the onset of symptoms; late detection can lead to profound and [...] Read more.

Newborn screening laboratories are increasingly adding lysosomal storage disorders (LSDs), such as Mucopolysaccharidosis I (MPS I) and Pompe disease, to their screening panels. Without newborn screening, LSDs are frequently diagnosed only after the onset of symptoms; late detection can lead to profound and irreversible organ damage and mortality. While screening of these disorders has accelerated over the past five years, there is little published information regarding the potential correlation of demographic variables (age at sample collection, birthweight, gestational age, gender, etc.) with lysosomal enzyme activity. The Missouri State Public Health Laboratory prospectively screened more than 475,000 newborns for MPS I, Pompe disease, Gaucher disease, and Fabry disease between 15 January 2013 and 15 May 2018. This report investigates trends between several demographic variables and activities of four lysosomal enzymes: α-L-iduronidase (IDUA), acid α-glucosidase (GAA), acid β-glucocerebrosidase (GBA), and acid α-galactosidase (GLA). This information provides a valuable resource to newborn screening laboratories for the implementation of screening for lysosomal storage disorders and the establishment of screening cutoffs. 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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15 pages, 4691 KiB

Open AccessArticle

Assessment and Application of Acylcarnitines Summations as Auxiliary Quantization Indicator for Primary Carnitine Deficiency

by Haijuan Zhi, Siyu Chang, Ting Chen, Lili Liang, Wenjuan Qiu, Huiwen Zhang, Xuefan Gu and Lianshu Han

Int. J. Neonatal Screen. 2025, 11(2), 47; https://doi.org/10.3390/ijns11020047 - 19 Jun 2025

Abstract

Background: Newborns are referred primary carnitine deficiency (PCD) when a low free carnitine (C0) concentration (<10 μmol/L) is detected, leading to high false-positive referrals. To improve the follow-up protocol for PCD, various acylcarnitines and the summations were comprehensively evaluated in the present study. [...] Read more.

Background: Newborns are referred primary carnitine deficiency (PCD) when a low free carnitine (C0) concentration (<10 μmol/L) is detected, leading to high false-positive referrals. To improve the follow-up protocol for PCD, various acylcarnitines and the summations were comprehensively evaluated in the present study. Methods: A retrospective study was performed using samples due to low C0 concentration. Data were available for 72 patients with genetically confirmed PCD, whereafter C0 with the selected sum of (butyrylcarnitine (C4) + isovalerylcarnitine (C5)) was validated in an additional cohort study including about 80,000 samples. Results: In the discovery study, C4, acetylcarnitine (C2) and C5 exhibited significant discriminant power in distinguishing PCDs from NoPCDs. The area under the ROC curve (AUC) was 99.792% (C4), 98.715% (C2) and 98.620% (C5). The excellent performances in sensitivity, specificity, negative predictive value, positive predictive value (PPV) and accuracy indexes suggested that C4, C2 and C5 would be ideal auxiliary indicators in improving the diagnostic performance of C0 for PCD. Multivariate ROC curve-based exploratory analysis showed that C5, C4 and C2 were the most top-ranked features in differentiating PCDs from NoPCDs. AUC for C4 + C5 was the highest with a cutoff required for 100% sensitivity at 0.181 μmol/L. In the validation cohort, adding C4 + C5 in the NBS program could elevate PPV from 0.75% to 1.54%. Conclusions: Our work revealed that C4 + C5 summation should be used as the auxiliary quantization indicator to reduce false-positive results for PCD. Full article

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10 pages, 652 KiB

Open AccessArticle

Nationwide Survey on Neonatal Critical Congenital Cardiopathies in Mexico: Data from 76 Public Health Service Hospital Units

by Nina Mendez-Dominguez, Ely Sanchez-Felix, Joan Johnson-Herrera, Miguel Santaularia-Tomas, Andres Ku-Gonzalez, Luis Baeza-Herrera, Adriel Ismael Alonso-Batun, Marcos Rivero-Peraza, Humberto Camara-Conde, Amonario Olivera-Mar and Russel Camara-Beltran

Int. J. Neonatal Screen. 2025, 11(2), 46; https://doi.org/10.3390/ijns11020046 - 16 Jun 2025

Abstract

When the resources are available, critical congenital heart diseases (CCHDs) should ideally be detected in utero; however, their later detection at birth can still reduce negative outcomes and risks. This study aimed to assess the extent of cardiac screening implementation in a national [...] Read more.

When the resources are available, critical congenital heart diseases (CCHDs) should ideally be detected in utero; however, their later detection at birth can still reduce negative outcomes and risks. This study aimed to assess the extent of cardiac screening implementation in a national sample of hospitals within Mexico’s public health services. A cross-sectional survey was conducted to identify the barriers and facilitators to neonatal screening using a sample of 76 hospitals. The descriptive statistics and associations were analyzed, with significance set at p < 0.05. Only 12% of hospitals reported the routine implementation of CCHD screening, while 20% used variable screening criteria. A potential mandatory implementation of CCHD screening was associated with increased odds of perceiving the lack of protocols and guidelines as a barrier. The most frequently reported obstacles involved a lack of the following: equipment, designated physical space, trained personnel, and adequate training. Nevertheless, the facilitators identified suggest that when combined with standardized guidelines and protocols, routine nationwide implementation may be achievable. Full article

(This article belongs to the Special Issue Equity Issues in Newborn Screening)

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10 pages, 208 KiB

Open AccessGuidelines

ISNS General Guidelines for Neonatal Bloodspot Screening 2025

by Dianne Webster, Amy Gaviglio, Aysha Habib Khan, Mei Baker, David Cheillan, Layachi Chabraoui, Ghassan Abdoh, Juan Cabello, Roberto Giugliani, Dimitris Platis, Jan Østrup, R. Rodney Howell, Peter C. J. I. Schielen and James R. Bonham

Int. J. Neonatal Screen. 2025, 11(2), 45; https://doi.org/10.3390/ijns11020045 - 14 Jun 2025

Abstract

Part of the vision of the ISNS is ‘to enhance the quality of neonatal screening and medical services through dissemination of information, guidelines and best practices.’ Although newborn screening encompasses testing in the newborn period for critical congenital heart disease, hearing impairment, birth [...] Read more.

Part of the vision of the ISNS is ‘to enhance the quality of neonatal screening and medical services through dissemination of information, guidelines and best practices.’ Although newborn screening encompasses testing in the newborn period for critical congenital heart disease, hearing impairment, birth defects, and congenital biochemical disorders (usually on bloodspots), this guideline is specifically about bloodspot screening. The ISNS has provided neonatal screening guidelines for many years and here presents the renewed 2025 General Guidelines for Neonatal Bloodspot Screening. They are intended to provide a framework for screening programs to develop specific policies around all aspects of the newborn screening system, offering the basic set of items for consideration. These guidelines provide trusted anchors to build, expand, or maintain robustly organized neonatal or newborn screening (NBS) programs and a checklist to evaluate and improve the essential elements of those programs. For starting or developing programs, it is a set of elements for which provisions need to be in place and a checklist of items that the screening program should at a minimum have provisions for. The publication of these guidelines is meant as a starting point for interactive discussion, to further improve this document and expand where necessary. Full article

7 pages, 191 KiB

Open AccessTechnical Note

Characterization of Dried Blood Spot Quality Control Materials for Lysosomal Enzyme Activity Assays Using Digital Microfluidic Fluorometry to Detect Lysosomal Storage Disorders in Newborns

by Paul Dantonio, Tracy Klug, Golriz Yazdanpanah, Christopher Haynes, Hui Zhou, Patrick Hopkins, Robert Vogt, Rachel Lee, Carla Cuthbert and Konstantinos Petritis

Int. J. Neonatal Screen. 2025, 11(2), 44; https://doi.org/10.3390/ijns11020044 - 10 Jun 2025

Abstract

Newborn bloodspot screening for one or more lysosomal storage disorders (NBS-LSD) is currently performed by many public health NBS laboratories globally. The screening tests measure activities of selected lysosomal enzymes on dried blood spot (DBS) specimens collected from newborns by the heel stick [...] Read more.

Newborn bloodspot screening for one or more lysosomal storage disorders (NBS-LSD) is currently performed by many public health NBS laboratories globally. The screening tests measure activities of selected lysosomal enzymes on dried blood spot (DBS) specimens collected from newborns by the heel stick method Because these assays measure enzyme activity, the quantitative results are dependent on the particular analytical method. DBS quality control (DBS QC) materials with assay-specific certified values that span the relevant range from typical to LSD-affected newborns are an important component of quality assurance in NBS laboratories. The Newborn Screening Quality Assurance Program (NSQAP) at the U.S. Centers for Disease Control and Prevention (CDC) provides public health NBS laboratories with DBS QC sets for NBS-LSD comprising four admixtures of pooled umbilical cord blood and a base pool made from leukodepleted peripheral blood and heat-inactivated serum. To evaluate the suitability of these materials for use with digital microfluidics fluorometry (DMF) assays which can currently measure the activity of four enzymes (acid α-galactosidase (GLA); acid β-glucocerebrosidase (GBA); acid α-glucosidase (GAA); and iduronidase (IDUA)), CDC collaborated with the Newborn Screening Unit at the Missouri State Public Health Laboratory (MSPHL). Using MSPHL criteria, we found that the certified results from each of two DBS QC lots collectively spanned the range from typical (screen negative) to enzyme deficient (screen positive) newborn DBS levels for each of the four lysosomal enzymes measured. The range included borderline results that would require repeat screening of the newborn under the MSPHL protocol. We conclude that these DBS QC preparations are suitable for use as external quality control materials for DMF assays used to detect LSDs in newborns. Full article

7 pages, 571 KiB

Open AccessArticle

Evaluation of Cystic Fibrosis Newborn Screening and Follow-Up Process in Georgia (2022–2023)

by Nino Vardosanidze, Nani Kavlashvili, Lali Margvelashvili, Oleg Kvlividze, Mikheil Diakonidze, Saba Iordanishvili and Dodo Agladze

Int. J. Neonatal Screen. 2025, 11(2), 43; https://doi.org/10.3390/ijns11020043 - 4 Jun 2025

Abstract

Cystic fibrosis (CF) is a chronic, autosomal-recessive disorder caused by mutations in the CFTR gene, leading to thickened secretions that affect multiple organ systems. This study examines the effectiveness of Georgia’s national CF screening program, which was initiated in 2012 and includes the [...] Read more.

Cystic fibrosis (CF) is a chronic, autosomal-recessive disorder caused by mutations in the CFTR gene, leading to thickened secretions that affect multiple organ systems. This study examines the effectiveness of Georgia’s national CF screening program, which was initiated in 2012 and includes the measurement of immunoreactive trypsinogen (IRT) levels at birth. An analysis of data from 2022 and 2023 revealed a decrease in follow-up attendance for sweat chloride testing among newborns with elevated IRT levels, from 59.9% to 51.2%. The birth prevalence of cystic fibrosis in Georgia varied, suggesting a need to improve both the accessibility of free testing and the quality of follow-up care. Identified barriers include limited access to screening results for pediatricians and the cost of follow-up tests. Recommendations include incorporating free sweat chloride and genetic testing into the national program, as well as improving community education and coordination with social agencies. The identification of 29 CFTR mutations in patients underscores the importance of continued genetic counseling. Overall, while the screening program shows promise, addressing these barriers is essential to improve outcomes and ensure the timely diagnosis and management of cystic fibrosis in Georgia. Full article

(This article belongs to the Special Issue Advances in Cystic Fibrosis Newborn Screening: From Laboratory Testing to Diagnosis)

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2 pages, 147 KiB

Open AccessEditorial

Ten-Year Anniversary of the International Journal of Neonatal Screening: Revisiting Its Scope

by Ralph Fingerhut and Peter C. J. I. Schielen

Int. J. Neonatal Screen. 2025, 11(2), 42; https://doi.org/10.3390/ijns11020042 - 4 Jun 2025

Abstract

The 10th anniversary of the International Journal of Neonatal Screening (IJNS) was celebrated on 25 March 2025, during the 13th Regional European Meeting of the International Society of Neonatal Screening (ISNS) in Luxembourg [...] Full article

13 pages, 382 KiB

Open AccessArticle

Informed Consent for Newborn Genomic Screening: Interest-Holder Perspectives on Dynamic Consent in an Evolving Landscape

by Marina Okamura, Emma Minchin, Carolyn Mazariego, Jolyn Hersch, Natalie Taylor and Ilona Juraskova

Int. J. Neonatal Screen. 2025, 11(2), 41; https://doi.org/10.3390/ijns11020041 - 28 May 2025

Abstract

Newborn Bloodspot Screening (NBS) has significantly advanced early disease detection, preventing severe disability and infant mortality. The anticipated integration of genomic technologies into NBS (gNBS) promises earlier diagnosis and targeted treatments. However, it also introduces complexities that necessitate enhanced consent processes. Dynamic Consent [...] Read more.

Newborn Bloodspot Screening (NBS) has significantly advanced early disease detection, preventing severe disability and infant mortality. The anticipated integration of genomic technologies into NBS (gNBS) promises earlier diagnosis and targeted treatments. However, it also introduces complexities that necessitate enhanced consent processes. Dynamic Consent Platforms (DCPs), with their layered information and modifiable preferences, may fulfil this rapidly evolving need. This qualitative study explored NBS and genomic interest-holder perspectives on (i) challenges in obtaining informed consent within the current and genomic NBS contexts, and (ii) the acceptability, feasibility, and utility of DCPs for genomics. Sixteen key interest-holders involved in NBS/genomic consent (midwives, genetic counsellors, geneticists, researchers, pathologist, consumer advocate) completed a semi-structured interview. Thematic analysis identified four main themes: (i) looking towards genomic expansions, (ii) systemic issues, (iii) genomic consent information, and (iv) Dynamic Consent Platforms. Participants emphasised revising the timing of consent processes and standardising consent training for clinicians. A nationally standardised DCP was perceived as valuable for addressing consent challenges within gNBS; however, concerns were raised regarding accessibility of online resources for vulnerable populations and integrating DCPs into healthcare systems. Recommendations for future research and clinical implications in this evolving field are discussed. Full article

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10 pages, 739 KiB

Open AccessArticle

Participatory Workflow Analysis of Newborn Genetic Screening (NBS) to Support Tools for Improved Follow-Up: Comparing the Use Case of Hemoglobinopathy Traits Across U.S. States

by Peter Taber, Jennifer Baysinger, Sierra Daniels, Natalie Diaz-Kincaid, Amy Gaviglio, Jacob Ginter, Patrice K. Held, Emily Reeves, Virginia Sack, Jennifer Weaver and Karen Eilbeck

Int. J. Neonatal Screen. 2025, 11(2), 40; https://doi.org/10.3390/ijns11020040 - 20 May 2025

Abstract

Communication of newborn screening (NBS) results often fails to provide clear explanations of NBS screen results to parents. Understanding existing NBS workflows is vital for improving NBS follow-up. We sought to describe a diverse range of state NBS programs as a starting point [...] Read more.

Communication of newborn screening (NBS) results often fails to provide clear explanations of NBS screen results to parents. Understanding existing NBS workflows is vital for improving NBS follow-up. We sought to describe a diverse range of state NBS programs as a starting point for designing tools to improve NBS follow-up, using the example of hemoglobinopathy traits. At a workshop of the 2023 Association of Public Health Laboratories NBS Symposium, participants filled out a survey and modeled their state workflows. Salient features were extracted and synthesized by state. A subset of models was member checked. Representatives from 19 U.S. states participated in the workflow analysis. Mail was overwhelmingly relied upon to convey the results. NBS programs differed by point of first contact with parents and degree of reliance on third parties. A participatory approach is useful for the rapid preliminary documentation of existing NBS program diversity and opportunities and challenges to improve patient education and follow-up. Future work should broaden the analysis to additional entities or individuals, particularly parents and caregivers. Full article

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3 pages, 139 KiB

Open AccessCommentary

It Takes All of Us: How the Cystic Fibrosis Foundation Is Supporting States in Advancing Cystic Fibrosis Newborn Screening

by Mary Dwight and Albert Faro

Int. J. Neonatal Screen. 2025, 11(2), 39; https://doi.org/10.3390/ijns11020039 - 20 May 2025

Abstract

The publication of Cystic Fibrosis Newborn Screening: A Systematic Review-Driven Consensus Guideline from the United States Cystic Fibrosis Foundation (CFF) presents the challenge of implementation. CFF is prepared to partner with stakeholders to enhance newborn screening (NBS) practices. Through funding provided to the [...] Read more.

The publication of Cystic Fibrosis Newborn Screening: A Systematic Review-Driven Consensus Guideline from the United States Cystic Fibrosis Foundation (CFF) presents the challenge of implementation. CFF is prepared to partner with stakeholders to enhance newborn screening (NBS) practices. Through funding provided to the Center for Public Health Innovation (CPHI), the CFF has helped establish two genetic testing resource centers to help states implement CFTR sequencing within the NBS algorithm. CPHI, with CFF funding, is facilitating quality improvement collaboratives that unite CF clinicians and NBS staff nationwide to share best practices in laboratory methods, communication, and education. CFF continues to fund the Screening Improvement Program Award for Optimizing the Diagnosis of Infants and has developed a toolkit to help CF care teams collaborate with NBS programs on guideline implementation. Together, these initiatives aim to support states and CF providers in adapting their algorithms and processes. By identifying current best practices to improve timeliness, sensitivity, and equity in CF NBS, CFF seeks to promote better outcomes for all individuals with CF. Recognizing the competing demands on state public health departments, CFF is committed to partnering with stakeholders to ensure meaningful improvements in CF NBS. Full article

(This article belongs to the Special Issue Advances in Cystic Fibrosis Newborn Screening: From Laboratory Testing to Diagnosis)

13 pages, 787 KiB

Open AccessArticle

Newborn Screening for Congenital Heart Disease: A Five-Year Study in Shanghai

by Youping Tian, Qing Gu, Xiaojing Hu, Xiaoling Ge, Xiaojing Ma, Miao Yang, Pin Jia, Jing Zhang, Lulu Yang, Quming Zhao, Fang Liu, Ming Ye, Yulin Yang and Guoying Huang

Int. J. Neonatal Screen. 2025, 11(2), 38; https://doi.org/10.3390/ijns11020038 - 17 May 2025

Abstract

This study aimed to report the progress and results of the newborn screening program for congenital heart disease (CHD) in south Shanghai between 2019 and 2023, and to evaluate the accuracy of the dual-index method (pulse oximetry (POX) plus cardiac murmur auscultation) in [...] Read more.

This study aimed to report the progress and results of the newborn screening program for congenital heart disease (CHD) in south Shanghai between 2019 and 2023, and to evaluate the accuracy of the dual-index method (pulse oximetry (POX) plus cardiac murmur auscultation) in clinical practice. Between 2019 and 2023, a total of 198,606 (99.89%) newborns were screened for CHD, of whom 3299 (1.66%) tested positive, 3043 (92.24%) underwent echocardiography for CHD diagnosis and 1109 were diagnosed with CHD in a timely manner. Among 195,307 infants with negative screening results using the dual-index method, 139 (0.07%) were later diagnosed with CHD, and none of these infants died. More than half of these false-negative infants (59.39%) were identified due to the detection of a heart murmur during routine physical examinations within six months after birth. Compared to POX testing alone, the dual-index method significantly improved the sensitivity of screening for CHD, and kept high specificity in clinical practice. This study demonstrated that newborn screening for CHD has been well conducted in Shanghai, and the dual-index method had high accuracy and reliability for neonatal CHD screening in clinical practice. Full article

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12 pages, 809 KiB

Open AccessArticle

Screening Blind Spot: Missing Preterm Infants in the Detection of Congenital Hypothyroidism

by Ashleigh Brown, Paul Hofman, Dianne Webster and Natasha Heather

Int. J. Neonatal Screen. 2025, 11(2), 37; https://doi.org/10.3390/ijns11020037 - 13 May 2025

Abstract

Congenital hypothyroidism (CH) is a critical condition in infancy where early detection is vital for optimal development. This study aimed to evaluate the sensitivity of Aotearoa New Zealand’s Newborn Metabolic Screening “Low Birth Weight” protocol for detecting CH in preterm infants. A 10-year [...] Read more.

Congenital hypothyroidism (CH) is a critical condition in infancy where early detection is vital for optimal development. This study aimed to evaluate the sensitivity of Aotearoa New Zealand’s Newborn Metabolic Screening “Low Birth Weight” protocol for detecting CH in preterm infants. A 10-year audit was conducted on 2935 preterm infants (<2000 g or ≤34 weeks gestation) screened within NICUs or SCBUs in the Auckland region. The study assessed both screen-detected and clinically detected cases of CH. Data were collected from screening and clinical records to evaluate the sensitivity and reliability of the current protocol. The audit identified 19 cases of primary CH, with a 1:154 incidence. Thirteen cases met the criteria for inclusion in the audit. Just over half of the eligible cases (7/13) were screen-detected, while the remaining were detected clinically, suggesting limitations in screening sensitivity. The analysis revealed that the protocol missed permanent as well as transient cases, and that biochemical severity was not predictive of permanence. A revised screening protocol was developed and commenced in July 2024. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital Hypothyroidism)

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12 pages, 977 KiB

Open AccessArticle

Characterization of C5 Acylcarnitines and Related Dicarboxylic Acylcarnitines in Saudi Newborns: Screening, Confirmation, and Cutoff Variation

by Hanadi A. Bokhari, Ahmed H. Mujamammi, Huda A. Bader, Hannadi J. Alamri and Khalid K. Alharbi

Int. J. Neonatal Screen. 2025, 11(2), 36; https://doi.org/10.3390/ijns11020036 - 12 May 2025

Abstract

Newborn screening (NBS) is a nationwide program for the early detection of disability in the Saudi population. This study focused on specific disorders related to organic acids that share C5 acylcarnitines derivatives and related dicarboxylic acylcarnitines as primary screening metabolites. We aimed to [...] Read more.

Newborn screening (NBS) is a nationwide program for the early detection of disability in the Saudi population. This study focused on specific disorders related to organic acids that share C5 acylcarnitines derivatives and related dicarboxylic acylcarnitines as primary screening metabolites. We aimed to determine the frequency of C5 acylcarnitine derivatives and related dicarboxylic acylcarnitines among screened newborns; confirm truly positive screening results using urine organic acid analysis; and compare the cutoff values for C5, C5DC, and C5OH acylcarnitines from the selected analytical centers. Data from laboratory positively screened and confirmed samples from the Public Health Authority (PHA) over 3 years were retrieved and analyzed to determine the frequency of the selected metabolites and percentage of true positive results among the positively screened samples. We identified significant correlations among variables such as disease, sex, and C5 metabolites across different cities. We clarified the frequency of true positive results for C5 acylcarnitine derivatives and related dicarboxylic acylcarnitines among Saudi newborns and highlighted significant variations in cutoff values across analytical centers. These findings contribute to the enhancement of NBS protocols and early intervention strategies. Full article

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16 pages, 1552 KiB

Open AccessArticle

Evaluation of the Performance of Newborn Screening for Tyrosinemia Type 1 in The Netherlands: Suggestions for Improvements Using Additional Biomarkers in Addition to Succinylacetone

by Marelle J. Bouva, Allysa M. Kuypers, Evelien A. Kemper, Rose E. Maase, Annet M. Bosch, Francjan J. van Spronsen, Annemieke C. Heijboer, M. Rebecca Heiner-Fokkema, Sandra G. Heil and Anita Boelen

Int. J. Neonatal Screen. 2025, 11(2), 35; https://doi.org/10.3390/ijns11020035 - 9 May 2025

Abstract

Currently, Dutch newborns are screened for tyrosinemia type 1 (TT1) using succinylacetone (SA) as the biomarker. Although the sensitivity of the test is high, a high number of false positives is observed. Here, the aim is to evaluate the current Dutch newborn-screening protocol [...] Read more.

Currently, Dutch newborns are screened for tyrosinemia type 1 (TT1) using succinylacetone (SA) as the biomarker. Although the sensitivity of the test is high, a high number of false positives is observed. Here, the aim is to evaluate the current Dutch newborn-screening protocol and to assess alternatives, specifically the use of biomarkers that are already being measured, to increase the positive predictive value (PPV). TT1 screening was performed with the Revvity NeoBase assay between 2008 and 2017, and since 2018, the Revvity NeoBase 2 assay has been used. Data from 2018 to 2021 were used for evaluation. To simulate alternative screening protocols, these data were enriched with results of referrals from other periods and a false negative (FN) from 2010. In 2018–2021, 693,821 newborns were screened, resulting in 23 referrals, of whom two were TT1 patients. For this period, to date, no FN have been reported, resulting in a provisional sensitivity of 100%, a specificity of 99.997%, and a PPV and negative predictive value of 9% and 100%, respectively. To improve the PPV, we combined SA, tyrosine (tyr), tyr × SA and tyr/phenylalanine and achieved a PPV of 72% for this dataset without introducing FN in the original dataset. This illustrates that future screening for TT1 may benefit from the addition of these biomarkers. Full article

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12 pages, 237 KiB

Open AccessArticle

Newborn Screening for Gaucher Disease: The New Jersey Experience

by Caitlin Menello, Shaney Pressley, Madeline Steffensen, Sarah Schmidt, Helio Pedro, Reena Jethva, Karen Valdez-Gonzalez, Darius J. Adams, Punita Gupta, Lorien Tambini King, Milen Velinov, Sharon Anderson, Peyman Bizargity, Beth Pletcher, Allysa Tuite, Christina Kresge, Debra Lynn Day-Salvatore, Ryan Kuehl and Can Ficicioglu

Int. J. Neonatal Screen. 2025, 11(2), 34; https://doi.org/10.3390/ijns11020034 - 2 May 2025

Abstract

Gaucher disease (GD) is a lysosomal storage disorder (LSD) characterized by glycosphingolipid accumulation. Age of symptomonset and disease progression varies across types of disease. Newborn screening (NBS) for Gaucher disease facilitates early identification of affected individuals and enables pre-symptomatic monitoring with the goal [...] Read more.

Gaucher disease (GD) is a lysosomal storage disorder (LSD) characterized by glycosphingolipid accumulation. Age of symptomonset and disease progression varies across types of disease. Newborn screening (NBS) for Gaucher disease facilitates early identification of affected individuals and enables pre-symptomatic monitoring with the goal of starting therapies early and improving clinical outcomes. This multi-center study involved New Jersey NBS referral centers. Data regarding initial NBS results, confirmatory testing, diagnosis, and treatment were collected. For patients on therapy, monitoring biomarkers and exam findings are available as of the last clinical evaluation. Between July 2019 and December 2023, 438,515 newborns were screened, with 60 screen-positive cases. Of those positive screens, 19 cases with positive screens did not undergo confirmatory testing due to parental refusal, loss to follow-up, or death; 23 cases were false positives; 14 newborns were diagnosed with GD type I; 2 newborns were diagnosed with suspected type I GD; 2 newborns were diagnosed with GD type II; and 1 case is still pending. Three type I GD patients started enzyme replacement therapy, with the youngest starting at 28 months of age. Post-treatment data are available for these individuals. One type II case was referred to experimental gene therapy, and one was started on ERT. Our results demonstrate that NBS for GD is a valuable public health tool that can facilitate early diagnosis and intervention. Full article

12 pages, 1057 KiB

Open AccessArticle

Characteristic Findings of Infants with Transient Elevation of Acylcarnitines in Neonatal Screening and Neonatal Weight Loss

by Sakura Morishima, Yumi Shimada, Yoriko Watanabe and Kenji Ihara

Int. J. Neonatal Screen. 2025, 11(2), 33; https://doi.org/10.3390/ijns11020033 - 29 Apr 2025

Abstract

The detection of elevated long-chain acylcarnitine levels, particularly C14:1 and the C14:1/C2 ratio, during neonatal screening may indicate very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), although similar findings can result from postnatal starvation. We investigated the relationship between false-positive results, postnatal weight loss, and subsequent [...] Read more.

The detection of elevated long-chain acylcarnitine levels, particularly C14:1 and the C14:1/C2 ratio, during neonatal screening may indicate very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), although similar findings can result from postnatal starvation. We investigated the relationship between false-positive results, postnatal weight loss, and subsequent growth. Additionally, we explored potential diagnostic markers of postnatal starvation. The following neonates from Oita Prefecture (April 2014–March 2024) were included in this study: patients identified as false-positive for VLCADD (n = 19), patients with VLCADD (n = 3), and children negative in mass screening who completed their 3-year-old health check-up (n = 30). The false-positive group exhibited significant weight loss at blood sampling for neonatal screening. An acylcarnitine analysis showed significant increases in various short- to long-chain fatty acids in the false-positive group, likely owing to enhanced fatty acid catabolism via β-oxidation. Elevation of a broad range of fatty acids and reduced amino acid levels seemed to be associated with significant weight loss at blood sampling. Full article

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15 pages, 893 KiB

Open AccessArticle

An Explorative Qualitative Study of the Role of a Genetic Counsellor to Parents Receiving a Diagnosis After a Positive Newborn Bloodspot Screening

by Samantha A. Sandelowsky, Alison McEwen, Jacqui Russell, Kirsten Boggs, Rosie Junek, Carolyn Ellaway, Arthavan Selvanathan, Michelle A. Farrar and Kaustuv Bhattacharya

Int. J. Neonatal Screen. 2025, 11(2), 32; https://doi.org/10.3390/ijns11020032 - 28 Apr 2025

Abstract

Newborn Bloodspot Screening (NBS) can detect severe treatable health conditions with onset during infancy. The parents of a newborn baby are vulnerable in the days after birth, and the optimal way to deliver the shocking and distressing news of a potential serious diagnosis [...] Read more.

Newborn Bloodspot Screening (NBS) can detect severe treatable health conditions with onset during infancy. The parents of a newborn baby are vulnerable in the days after birth, and the optimal way to deliver the shocking and distressing news of a potential serious diagnosis is yet to be defined. More data are needed to determine whether access to a genetic counsellor (GC) improves families’ experiences with genetic conditions identified by NBS. This study aimed to explore the similarities and differences for parents who received a positive NBS result for Spinal Muscular Atrophy (SMA) and received access to a GC (GC cohort), to a cohort of parents who received a diagnosis for inborn errors of metabolism (IEM) and did not have access to a GC (non-GC cohort). Semi-structured interviews explored the retrospective experiences of receiving the NBS result, including diagnosis implications and subsequent adaptation to respective genetic diagnoses. Inductive thematic analysis was used from group comparison. 7 SMA families and 5 IEM families were included in the study. Four themes were identified: 1. minimal pre-test counselling; 2. perceived lack of local healthcare team knowledge; 3. enabling factors for adaptation; 4. implications for both individuals and their families. Both the GC and non-GC cohorts reported insufficient counselling in the pre-test period and described feeling traumatised at the time of the diagnosis delivery. Families without subsequent GC input described limited understanding of the disease due to the use of medicalized terms, as well as a decreased understanding of reproductive options, familial communication and subsequent cascade screening. GCs can support information needs and adaptation following a NBS diagnosis. Full article

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16 pages, 1489 KiB

Open AccessArticle

Expanded Newborn Screening in Italy: The First Report of Lombardy Region

by Clarissa Berardo, Alessandra Vasco, Alessia Mauri, Simona Lucchi, Laura Cappelletti, Laura Saielli, Manuela Rizzetto, Davide Biganzoli, Cristina Montrasio, Diana Postorivo, Elisa Pratiffi, Andrea Meta, Stephana Carelli, Alessandro Amorosi, Sabrina Paci, Graziella Cefalo, Francesca Furlan, Francesca Menni, Serena Gasperini, Viola Crescitelli, Giuseppe Banderali, Gianvincenzo Zuccotti, Luisella Alberti and Cristina Cereda Show full author list Hide full author list

Int. J. Neonatal Screen. 2025, 11(2), 31; https://doi.org/10.3390/ijns11020031 - 25 Apr 2025

Abstract

Background: Newborn screening (NBS) is a preventive healthcare program aiming at identifying the inborn errors of metabolism (IEMs) in asymptomatic infants to reduce the risk of severe complications. The aim of this study was to report the first years (2016–2020) of the expanded [...] Read more.

Background: Newborn screening (NBS) is a preventive healthcare program aiming at identifying the inborn errors of metabolism (IEMs) in asymptomatic infants to reduce the risk of severe complications. The aim of this study was to report the first years (2016–2020) of the expanded NBS program in the Lombardy region, Italy. Methods: Dried blood spots were collected from newborns’ heels at 48–72 h after birth. FIA-MS/MS was performed to evaluate specific biochemical markers. Genetic confirmation was achieved via Sanger or NGS on newborns and reported to a clinical reference center (CRC). Results: A total of 343,507 newborns were tested; 1414/343,507 resulted as positive to NBS and were reported to the CRC. A total of 209 newborns were diagnosed with IEMs: 206 infants received a diagnosis of IEM through NBS, confirmed by genetic analysis; three neonates were not positive to NBS but were subsequentially diagnosed with IEMs. A total of 1208/343,507 were false positive cases. Twenty-seven types of IEMs were diagnosed in 209 patients: 111 newborns were affected by aminoacidemias, 11 by urea cycle disorders, 27 by organic acidemias, 34 by fatty acid oxidation disorders, and 26 by secondary conditions. Conclusions: We report here for the first time the IEM incidence and distribution in the Lombardy region in the first five years of NBS. Full article

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Open AccessArticle

Newborn Screening for Metachromatic Leukodystrophy in Tuscany: The Paradigm of a Successful Preventive Medicine Program

by Sabrina Malvagia, Alessandra Bettiol, Margherita Porcaro, Massimo Mura, Silvia Funghini, Daniela Ombrone, Giulia Forni, Emanuela Scolamiero, Filippo Coppi, Roberta Damiano, Cristina Cereda, Simonetta Simonetti, Annalisa Lonetti, Marta Daniotti, Anna Caciotti, Amelia Morrone, Valeria Calbi, Francesca Fumagalli, Alessandro Aiuti, Elena Procopio, Renzo Guerrini and Giancarlo la Marca Show full author list Hide full author list

Int. J. Neonatal Screen. 2025, 11(2), 30; https://doi.org/10.3390/ijns11020030 - 24 Apr 2025

Abstract

Metachromatic leukodystrophy (MLD) is a rare inherited disorder of lysosomal storage, caused by a deficiency in the arylsulfatase A (ARSA) enzyme, leading to toxic accumulation of sulfatides, which progressively impair motor and cognitive function. MLD is a candidate for inclusion in newborn screening [...] Read more.

Metachromatic leukodystrophy (MLD) is a rare inherited disorder of lysosomal storage, caused by a deficiency in the arylsulfatase A (ARSA) enzyme, leading to toxic accumulation of sulfatides, which progressively impair motor and cognitive function. MLD is a candidate for inclusion in newborn screening (NBS) programs, due to the narrow pre-symptomatic window for effective therapeutic intervention. We set up a prospective pilot NBS program for MLD in Tuscany, based on a two-step approach. The first-tier test quantified four sulfatides; if levels exceeded the cut-off, we performed the second-tier test by measuring ARSA activity on the same neonatal dried blood spot (DBS). We performed the first-tier test on 42,262 newborns over two years and the second-tier test on residual neonatal DBS from 90 of them (0.21%). We recalled 10 newborns (0.02%) for an additional DBS, due to insufficient residual material for a second-tier test (n = 4) or to low ARSA activity (n = 6). We found normal ARSA activity in all new DBS and identified no new cases of MLD. Retrospective analysis of eight neonatal and fifteen non-neonatal DBS from patients with genetically confirmed MLD showed that the algorithm accurately identified MLD patients. This diagnostic algorithm proved feasible and accurate for early detection of MLD in prospective NBS. Full article

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International Journal of Neonatal Screening

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