International Journal of Neonatal Screening

184 pages, 9791 KiB

Open AccessEditor’s ChoiceReview

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

by Bradford L. Therrell, Carmencita D. Padilla, Gustavo J. C. Borrajo, Issam Khneisser, Peter C. J. I. Schielen, Jennifer Knight-Madden, Helen L. Malherbe and Marika Kase

Int. J. Neonatal Screen. 2024, 10(2), 38; https://doi.org/10.3390/ijns10020038 - 23 May 2024

Cited by 7 | Viewed by 10059

Abstract

Newborn bloodspot screening (NBS) began in the early 1960s based on the work of Dr. Robert “Bob” Guthrie in Buffalo, NY, USA. His development of a screening test for phenylketonuria on blood absorbed onto a special filter paper and transported to a remote [...] Read more.

Newborn bloodspot screening (NBS) began in the early 1960s based on the work of Dr. Robert “Bob” Guthrie in Buffalo, NY, USA. His development of a screening test for phenylketonuria on blood absorbed onto a special filter paper and transported to a remote testing laboratory began it all. Expansion of NBS to large numbers of asymptomatic congenital conditions flourishes in many settings while it has not yet been realized in others. The need for NBS as an efficient and effective public health prevention strategy that contributes to lowered morbidity and mortality wherever it is sustained is well known in the medical field but not necessarily by political policy makers. Acknowledging the value of national NBS reports published in 2007, the authors collaborated to create a worldwide NBS update in 2015. In a continuing attempt to review the progress of NBS globally, and to move towards a more harmonized and equitable screening system, we have updated our 2015 report with information available at the beginning of 2024. Reports on sub-Saharan Africa and the Caribbean, missing in 2015, have been included. Tables popular in the previous report have been updated with an eye towards harmonized comparisons. To emphasize areas needing attention globally, we have used regional tables containing similar listings of conditions screened, numbers of screening laboratories, and time at which specimen collection is recommended. Discussions are limited to bloodspot screening. Full article

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18 pages, 304 KiB

Open AccessEditor’s ChoiceArticle

Experiences of Families Caring for Children with Newborn Screening-Related Conditions: Implications for the Expansion of Genomics in Population-Based Neonatal Public Health Programs

by Lynn Bush, Hannah Davidson, Shani Gelles, Dawn Lea and Laura M. Koehly

Int. J. Neonatal Screen. 2022, 8(2), 35; https://doi.org/10.3390/ijns8020035 - 23 May 2022

Cited by 12 | Viewed by 3497

Abstract

With the expansion of newborn screening conditions globally and the increased use of genomic technologies for early detection, there is a need for ethically nuanced policies to guide the future integration of ever-more comprehensive genomics into population-based newborn screening programs. In the current [...] Read more.

With the expansion of newborn screening conditions globally and the increased use of genomic technologies for early detection, there is a need for ethically nuanced policies to guide the future integration of ever-more comprehensive genomics into population-based newborn screening programs. In the current paper, we consider the lived experiences of 169 family caregivers caring for 77 children with NBS-related conditions to identify lessons learned that can inform policy and practice related to population-based newborn screening using genomic technologies. Based on caregiver narratives obtained through in-depth interviews, we identify themes characterizing these families’ diagnostic odyssey continuum, which fall within two domains: (1) medical management implications of a child diagnosed with an NBS-related condition and (2) psychological implications of a child diagnosed with an NBS-related condition. For Domain 1, family caregivers’ experiences point to the need for educational resources for both health care professionals that serve children with NBS-related conditions and their families; empowerment programs for family caregivers; training for providers in patient-centered communication; and access to multi-disciplinary specialists. For Domain 2, caregivers’ experiences suggest a need for access to continuous, long-term counseling resources; patient navigator resources; and peer support programs. These lessons learned can inform policy recommendations for the benefit of the child, the family, the healthcare system, and society. Full article

(This article belongs to the Special Issue Ethical and Psychosocial Aspects of Genomics in the Neonatal Period)

13 pages, 792 KiB

Open AccessEditor’s ChoiceReview

Future Perspectives of Newborn Screening for Inborn Errors of Immunity

by Maartje Blom, Robbert G. M. Bredius and Mirjam van der Burg

Int. J. Neonatal Screen. 2021, 7(4), 74; https://doi.org/10.3390/ijns7040074 - 2 Nov 2021

Cited by 12 | Viewed by 4478

Abstract

Newborn screening (NBS) programs continue to expand due to innovations in both test methods and treatment options. Since the introduction of the T-cell receptor excision circle (TREC) assay 15 years ago, many countries have adopted screening for severe combined immunodeficiency (SCID) in their [...] Read more.

Newborn screening (NBS) programs continue to expand due to innovations in both test methods and treatment options. Since the introduction of the T-cell receptor excision circle (TREC) assay 15 years ago, many countries have adopted screening for severe combined immunodeficiency (SCID) in their NBS program. SCID became the first inborn error of immunity (IEI) in population-based screening and at the same time the TREC assay became the first high-throughput DNA-based test in NBS laboratories. In addition to SCID, there are many other IEI that could benefit from early diagnosis and intervention by preventing severe infections, immune dysregulation, and autoimmunity, if a suitable NBS test was available. Advances in technologies such as KREC analysis, epigenetic immune cell counting, protein profiling, and genomic techniques such as next-generation sequencing (NGS) and whole-genome sequencing (WGS) could allow early detection of various IEI shortly after birth. In the next years, the role of these technical advances as well as ethical, social, and legal implications, logistics and cost will have to be carefully examined before different IEI can be considered as suitable candidates for inclusion in NBS programs. Full article

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17 pages, 936 KiB

Open AccessEditor’s ChoiceArticle

Use of Molecular Genetic Analyses in Danish Routine Newborn Screening

by Allan Meldgaard Lund, Flemming Wibrand, Kristin Skogstrand, Marie Bækvad-Hansen, Niels Gregersen, Brage Storstein Andresen, David M. Hougaard, Morten Dunø and Rikke Katrine Jentoft Olsen

Int. J. Neonatal Screen. 2021, 7(3), 50; https://doi.org/10.3390/ijns7030050 - 26 Jul 2021

Cited by 13 | Viewed by 4198

Abstract

Historically, the analyses used for newborn screening (NBS) were biochemical, but increasingly, molecular genetic analyses are being introduced in the workflow. We describe the application of molecular genetic analyses in the Danish NBS programme and show that second-tier molecular genetic testing is useful [...] Read more.

Historically, the analyses used for newborn screening (NBS) were biochemical, but increasingly, molecular genetic analyses are being introduced in the workflow. We describe the application of molecular genetic analyses in the Danish NBS programme and show that second-tier molecular genetic testing is useful to reduce the false positive rate while simultaneously providing information about the precise molecular genetic variant and thus informing therapeutic strategy and easing providing information to parents. When molecular genetic analyses are applied as second-tier testing, valuable functional data from biochemical methods are available and in our view, such targeted NGS technology should be implemented when possible in the NBS workflow. First-tier NGS technology may be a promising future possibility for disorders without a reliable biomarker and as a general approach to increase the adaptability of NBS for a broader range of genetic diseases, which is important in the current landscape of quickly evolving new therapeutic possibilities. However, studies on feasibility, sensitivity, and specificity are needed as well as more insight into what views the general population has towards using genetic analyses in NBS. This may be sensitive to some and could have potentially negative consequences for the NBS programme. Full article

(This article belongs to the Special Issue Next Generation Sequencing (NGS) in Newborn Screening)

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7 pages, 670 KiB

Open AccessEditor’s ChoiceCase Report

Low Psychosine in Krabbe Disease with Onset in Late Infancy: A Case Report

by Camille S. Corre, Dietrich Matern, Joan E. Pellegrino, Carlos A. Saavedra-Matiz, Joseph J. Orsini and Robert Thompson-Stone

Int. J. Neonatal Screen. 2021, 7(2), 28; https://doi.org/10.3390/ijns7020028 - 28 May 2021

Cited by 5 | Viewed by 3328

Abstract

Krabbe disease (KD) is a rare inherited neurodegenerative disorder caused by a deficiency in galactocerebrosidase enzyme activity, which can present in early infancy, requiring an urgent referral for hematopoietic stem cell transplantation, or later in life. Newborn screening (NBS) for KD requires identification [...] Read more.

Krabbe disease (KD) is a rare inherited neurodegenerative disorder caused by a deficiency in galactocerebrosidase enzyme activity, which can present in early infancy, requiring an urgent referral for hematopoietic stem cell transplantation, or later in life. Newborn screening (NBS) for KD requires identification and risk-stratification of patients based on laboratory values to predict disease onset in early infancy or later in life. The biomarker psychosine plays a key role in NBS algorithms to ascertain probability of early-onset disease. This report describes a patient who was screened positive for KD in New York State, had a likely pathogenic genotype, and showed markedly reduced enzyme activity but surprisingly low psychosine levels. The patient ultimately developed KD in late infancy, an outcome not clearly predicted by existing NBS algorithms. It remains critical that psychosine levels be evaluated alongside genotype, enzyme activity levels, and the patient’s evolving clinical presentation, ideally in consultation with experts in KD, in order to guide diagnosis and plans for monitoring. Full article

(This article belongs to the Special Issue Newborn Screening and Follow-Up Diagnostic Testing for Krabbe Disease)

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8 pages, 224 KiB

Open AccessEditor’s ChoiceArticle

Newborn Screening for Krabbe Disease—Illinois Experience: Role of Psychosine in Diagnosis of the Disease

by Khaja Basheeruddin, Rong Shao, Fran Balster, Pearlie Gardley and Laura Ashbaugh

Int. J. Neonatal Screen. 2021, 7(2), 24; https://doi.org/10.3390/ijns7020024 - 9 May 2021

Cited by 14 | Viewed by 3754

Abstract

Population-based newborn screening for Krabbe disease was initiated by measurement of galactocerebrosidase (GALC) activity in the state of Illinois in December 2017. Due to the poor specificity of GALC for the diagnosis of Krabbe disease, second-tier testing services were provided to reduce the [...] Read more.

Population-based newborn screening for Krabbe disease was initiated by measurement of galactocerebrosidase (GALC) activity in the state of Illinois in December 2017. Due to the poor specificity of GALC for the diagnosis of Krabbe disease, second-tier testing services were provided to reduce the false positive rates for disease monitoring. Using ultra-pressure liquid chromatography coupled to mass spectrometry assay, a total of 497,147 newborns were screened. In total, 288 infants’ specimens (0.06%) having reduced GALC activity were sent out for second-tier testing to a reference laboratory. All newborns’ reduced GALC specimens were tested for psychosine levels, the presence of a 30-kb deletion and GALC sequencing. The results showed that two infants had elevated psychosine levels (10 and 35 nM) and were referred immediately for evaluation and treatment for Infantile Krabbe disease, and six infants had intermediate PSY levels (≥2 to 5 nM) and are under observation as suspected candidates for late-onset Krabbe disease. In addition, 178 infants had pseudodeficiency alleles, all having psychosine levels < 2.0 nM. Our data show that a high percentage of reduced GALC activity (62%) was due to the presence of pseudodeficiency alleles in the GALC gene. In conclusion, incorporation of psychosine measurements can identify infants with infantile Krabbe disease and probable late-onset Krabbe infants. Furthermore, Krabbe disease screening can be achieved at public health laboratories, and infants with infantile Krabbe disease can be diagnosed in timely manner for better outcome. Full article

(This article belongs to the Special Issue Newborn Screening and Follow-Up Diagnostic Testing for Krabbe Disease)

10 pages, 1665 KiB

Open AccessEditor’s ChoiceArticle

A Voluntary Statewide Newborn Screening Pilot for Spinal Muscular Atrophy: Results from Early Check

by Katerina S. Kucera, Jennifer L. Taylor, Veronica R. Robles, Kristin Clinard, Brooke Migliore, Beth Lincoln Boyea, Katherine C. Okoniewski, Martin Duparc, Catherine W. Rehder, Scott M. Shone, Zheng Fan, Melissa Raspa, Holly L. Peay, Anne C. Wheeler, Cynthia M. Powell, Donald B. Bailey and Lisa M. Gehtland

Int. J. Neonatal Screen. 2021, 7(1), 20; https://doi.org/10.3390/ijns7010020 - 21 Mar 2021

Cited by 20 | Viewed by 4809

Abstract

Prior to statewide newborn screening (NBS) for spinal muscular atrophy (SMA) in North Carolina, U.S.A., we offered voluntary screening through the Early Check (EC) research study. Here, we describe the EC experience from October 2018 through December 2020. We enrolled a total of [...] Read more.

Prior to statewide newborn screening (NBS) for spinal muscular atrophy (SMA) in North Carolina, U.S.A., we offered voluntary screening through the Early Check (EC) research study. Here, we describe the EC experience from October 2018 through December 2020. We enrolled a total of 12,065 newborns and identified one newborn with 0 copies of SMN1 and two copies of SMN2, consistent with severe early onset of SMA. We also detected one false positive result, likely stemming from an unrelated blood disorder associated with a low white blood cell count. We evaluated the timing of NBS for babies enrolled prenatally (n = 932) and postnatally (n = 11,133) and reasons for delays in screening and reporting. Although prenatal enrollment led to faster return of results (median = 13 days after birth), results for babies enrolled postnatally were still available within a timeframe (median = 21 days after birth) that allowed the opportunity to receive essential treatment early in life. We evaluated an SMA q-PCR screening method at two separate time points, confirming the robustness of the assay. The pilot project provided important information about SMA screening in anticipation of forthcoming statewide expansion as part of regular NBS. Full article

(This article belongs to the Special Issue Newborn Screening for Spinal Muscular Atrophy)

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27 pages, 2897 KiB

Open AccessEditor’s ChoiceArticle

Neonatal Urine Screening Program in the Province of Quebec: Technological Upgrade from Thin Layer Chromatography to Tandem Mass Spectrometry

by Christiane Auray-Blais, Michel Boutin, Pamela Lavoie and Bruno Maranda

Int. J. Neonatal Screen. 2021, 7(1), 18; https://doi.org/10.3390/ijns7010018 - 20 Mar 2021

Cited by 7 | Viewed by 4115

Abstract

The Quebec Neonatal Urine Screening Program was initiated in 1971 with overall screening inception of newborns in 1973. Forty-seven years later, over 3.5 million babies have been screened for up to 25 inborn errors of metabolism divided into two groups: (1) urea cycle [...] Read more.

The Quebec Neonatal Urine Screening Program was initiated in 1971 with overall screening inception of newborns in 1973. Forty-seven years later, over 3.5 million babies have been screened for up to 25 inborn errors of metabolism divided into two groups: (1) urea cycle disorders and organic acidurias; and (2) disorders of amino acid metabolism and transport. The main goal of this preventive genetic medicine program is the detection of treatable diseases before the onset of clinical symptoms. Urine specimens from 21-day-old babies are collected and dried on filter paper by parents at home. The participation is voluntary with a high compliance rate over the years (~90%). Specimens are analyzed by thin layer chromatography (TLC). The main objective of this evaluative research project was to assess the feasibility of a technological upgrade towards mass spectrometry. A 2.85-min flow injection method was devised, normal values established, and abnormal profiles confirmed using second-tier tests. The validated assays are sensitive, specific, and suitable for populational screening, as well as for high-risk screening laboratories. Triple H syndrome, which would not be detected in newborns by blood screening at two days of age was found to be positive in the urine of an affected patient. Full article

(This article belongs to the Special Issue Tandem Mass Spectrometry in Newborn Screening)

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31 pages, 1282 KiB

Open AccessEditor’s ChoiceArticle

We All Have a Role to Play: Redressing Inequities for Children Living with CAH and Other Chronic Health Conditions of Childhood in Resource-Poor Settings

by Kate Armstrong, Alain Benedict Yap, Sioksoan Chan-Cua, Maria E. Craig, Catherine Cole, Vu Chi Dung, Joseph Hansen, Mohsina Ibrahim, Hassana Nadeem, Aman Pulungan, Jamal Raza, Agustini Utari and Paul Ward

Int. J. Neonatal Screen. 2020, 6(4), 76; https://doi.org/10.3390/ijns6040076 - 25 Sep 2020

Cited by 11 | Viewed by 6668

Abstract

CLAN (Caring and Living as Neighbours) is an Australian-based non-governmental organisation (NGO) committed to equity for children living with chronic health conditions in resource-poor settings. Since 2004, CLAN has collaborated with a broad range of partners across the Asia Pacific region to improve [...] Read more.

CLAN (Caring and Living as Neighbours) is an Australian-based non-governmental organisation (NGO) committed to equity for children living with chronic health conditions in resource-poor settings. Since 2004, CLAN has collaborated with a broad range of partners across the Asia Pacific region to improve quality of life for children living with congenital adrenal hyperplasia (CAH). This exploratory case study uses the Knowledge to Action (KTA) framework to analyse CLAN’s activities for children living with CAH in the Asia Pacific. The seven stages of the KTA action cycle inform a systematic examination of comprehensive, collaborative, sustained actions to address a complex health challenge. The KTA framework demonstrates the “how” of CLAN’s approach to knowledge creation and exchange, and the centrality of community development to multisectoral collaborative action across a range of conditions, cultures and countries to redressing child health inequities. This includes a commitment to: affordable access to essential medicines and equipment; education, research and advocacy; optimisation of medical management; encouragement of family support groups; efforts to reduce financial burdens; and ethical, transparent program management as critical components of success. Improvements in quality of life and health outcomes are achievable for children living with CAH and other chronic health conditions in resource-poor settings. CLAN’s strategic framework for action offers a model for those committed to #LeaveNoChildBehind. Full article

(This article belongs to the Special Issue CAH Screening—Challenges and Opportunities)

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