Special Issue "Newborn Screening for Sickle Cell Disease and other Haemoglobinopathies"

A special issue of International Journal of Neonatal Screening (ISSN 2409-515X).

Deadline for manuscript submissions: closed (30 September 2018)

Special Issue Editors

Guest Editor
Dr. med. Stephan Lobitz

Amsterdam Street Children's Hospital Cologne, Department of Pediatric Oncology and Hematology, Amsterdamer Str. 59, 50735 Cologne, Germany
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Interests: sickle cell disease, thalassemia, hemoglobinopathies, newborn screening, digital health interventions
Guest Editor
Prof. Jacques Elion

Université Paris Diderot-USPC - Inserm UMR1134 ‘Biologie Intégrée du Globule Rouge’, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, 75015 Paris, France
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Guest Editor
Dr. Raffaella Colombatti

Clinic of Pediatric Hematology Oncology, Department of Child and Maternal Health Azienda Ospedaliera - Università di Padova Via Giustiniani 3, 35129 Padova, Italy
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Guest Editor
Dr. Elena Cela

Médico Adjunto. Hematología-Oncología pediátricas. Facultad de Medicina. Universidad Complutense de Madrid; Hospital G. Universitario Gregorio Marañón. C/ Maiquez 5. 28007 Madrid.
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Special Issue Information

Sickle cell disease is a severe, hereditary, non-malignant disorder of hemoglobin based on homozygous or compound heterozygous mutations in the β globin genes. Life-threatening complications may occur as early as age three months and are most commonly related to infections by encapsulated bacteria. Thus, they are largely preventable by appropriate preventive measures including vaccinations, penicillin prophylaxis and the education of parents, provided that the diagnosis has been previously established. For this reason, sickle cell disease is the target disease of several national newborn screening programs.

β thalassemias are a very heterogeneous group of blood disorders. The huge spectrum of clinical variability includes asymptomatic and oligosymptomatic states (β thalassemia minor, mild forms of β thalassemia intermedia) as well as significant to severe manifestations associated with high morbidity and mortality (more severe forms of β thalassemia intermedia and β thalassemia major). Severe forms of β thalassemia major can be diagnosed as a byproduct of neonatal screening for sickle cell disease. However, originary neonatal screening for β thalassemia alone does not fulfill the (modified) Wilson Jungner criteria and is not justified. Nevertheless, there is broad consensus among experts that screening results that raise suspicion of significant β thalassemia disease states should be reported.

α thalassemias are not as heterogeneous as β thalassemias. Most genotypes are not associated with a significant phenotype. However, occasionally, severe forms of α thalassemia, e.g. HbH/Constant Spring disease may cause suspicious results in newborn screening for
β hemoglobinopathies.

The Special Issue on newborn screening for hemoglobinopathies of the International Journal of Neonatal Screening will focus on the state-of-the-art of the neonatal diagnosis of disorders of hemoglobin with an emphasis on sickle cell disease. It will also provide insight into the genetic and pathophysiological background of sickle cell disease, as well as into its clinical course and contemporary treatment in high resource countries.

The following topics could be interesting for the reader. Some are taken from the program of the Pan-European Conference on Newborn Screening for Hemoglobinopathies. It is likely that many speakers at this conference will be willing to contribute to this Special Issue:

  1. Sickle cell disease (genetics, pathophysiology, clinical presentation and treatment)
  2. Alpha and beta thalassemia (genetics, pathophysiology, clinical presentation and treatment)
  3. The changing epidemiology of sickle cell disease (SCD) in Europe: past, present and future
  4. Newborn screening (NBS) for hemoglobinopathies - where are we in 2018?
  5. Classical screening methods (IEF/HPLC/CE)
  6. Point-of-care diagnostics
  7. MALDI-TOF MS
  8. Tandem-MS
  9. Targeted versus universal NBS? Information of carriers?
  10. An overview of NBS for hemoglobinopathies in several countries (can be subdivided)
  11. North–South collaboration on SCD: a global view

Dr. Stephan Lobitz
Prof. Jacques Elion
Dr. Raffaella Colombatti
Dr. Elena Cela
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Neonatal Screening is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 500 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (15 papers)

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Editorial

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Open AccessEditorial European Union Should Actively Stimulate and Harmonise Neonatal Screening Initiatives
Int. J. Neonatal Screen. 2018, 4(4), 32; https://doi.org/10.3390/ijns4040032
Received: 27 September 2018 / Revised: 7 November 2018 / Accepted: 8 November 2018 / Published: 14 November 2018
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Abstract
Neonatal screening programmes have been introduced in almost all European countries. In practice there are large differences, especially in the panel of conditions that are screened for, often without clear reasons. Policy making on a European level is lacking in contrast to the [...] Read more.
Neonatal screening programmes have been introduced in almost all European countries. In practice there are large differences, especially in the panel of conditions that are screened for, often without clear reasons. Policy making on a European level is lacking in contrast to the situation in the USA. Professionals have the knowledge to expand the panels but are dependent on policy-makers for the necessary funds. This paper is a call on the EU Commission to take up a role in providing equal access to neonatal screening for all children within the EU. Full article

Research

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Open AccessArticle A Multicentre Pilot Study of a Two-Tier Newborn Sickle Cell Disease Screening Procedure with a First Tier Based on a Fully Automated MALDI-TOF MS Platform
Int. J. Neonatal Screen. 2019, 5(1), 10; https://doi.org/10.3390/ijns5010010
Received: 4 December 2018 / Revised: 19 January 2019 / Accepted: 21 January 2019 / Published: 23 January 2019
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Abstract
The reference methods used for sickle cell disease (SCD) screening usually include two analytical steps: a first tier for differentiating haemoglobin S (HbS) heterozygotes, HbS homozygotes and β-thalassemia from other samples, and a confirmatory second tier. Here, we evaluated a first-tier approach based [...] Read more.
The reference methods used for sickle cell disease (SCD) screening usually include two analytical steps: a first tier for differentiating haemoglobin S (HbS) heterozygotes, HbS homozygotes and β-thalassemia from other samples, and a confirmatory second tier. Here, we evaluated a first-tier approach based on a fully automated matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) platform with automated sample processing, a laboratory information management system and NeoSickle® software for automatic data interpretation. A total of 6701 samples (with high proportions of phenotypes homozygous (FS) or heterozygous (FAS) for the inherited genes for sickle haemoglobin and samples from premature newborns) were screened. The NeoSickle® software correctly classified 98.8% of the samples. This specific blood sample collection was enriched in qualified difficult samples (premature newborns, FAS samples, late and very late samples, etc.). In this study, the sensitivity of FS sample detection was found to be 100% on the Lille MS facility and 99% on the Dijon MS facility, and the specificity of FS sample detection was found to be 100% on both MS facilities. The MALDI-MS platform appears to be a robust solution for first-tier use to detect the HbS variant: it is reproducible and sensitive, it has the power to analyze 600–1000 samples per day and it can reduce the unit cost of testing thanks to maximal automation, minimal intervention by the medical team and good overall practicability. The MALDI-MS approach meets today’s criteria for the large-scale, cost-effective screening of newborns, children and adults. Full article
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Open AccessArticle Newborn Screening for Sickle Cell Disease in the Caribbean: An Update of the Present Situation and of the Disease Prevalence
Int. J. Neonatal Screen. 2019, 5(1), 5; https://doi.org/10.3390/ijns5010005
Received: 13 November 2018 / Revised: 7 December 2018 / Accepted: 1 January 2019 / Published: 8 January 2019
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Abstract
The region surrounding the Caribbean Sea is predominantly composed of island nations for its Eastern part and the American continental coast on its Western part. A large proportion of the population, particularly in the Caribbean islands, traces its ancestry to Africa as a [...] Read more.
The region surrounding the Caribbean Sea is predominantly composed of island nations for its Eastern part and the American continental coast on its Western part. A large proportion of the population, particularly in the Caribbean islands, traces its ancestry to Africa as a consequence of the Atlantic slave trade during the XVI–XVIII centuries. As a result, sickle cell disease has been largely introduced in the region. Some Caribbean countries and/or territories, such as Jamaica and the French territories, initiated newborn screening (NBS) programs for sickle cell disease more than 20 years ago. They have demonstrated the major beneficial impact on mortality and morbidity resulting from early childhood care. However, similar programs have not been implemented in much of the region. This paper presents an update of the existing NBS programs and the prevalence of sickle cell disease in the Caribbean. It demonstrates the impact of the Caribbean Network of Researchers on Sickle Cell Disease and Thalassemia (CAREST) on the extension of these programs. The presented data illustrate the importance of advocacy in convincing policy makers of the feasibility and benefit of NBS for sickle cell disease when coupled to early care. Full article
Open AccessArticle Evaluation of Technical Issues in a Pilot Multicenter Newborn Screening Program for Sickle Cell Disease
Int. J. Neonatal Screen. 2019, 5(1), 2; https://doi.org/10.3390/ijns5010002
Received: 30 October 2018 / Revised: 18 December 2018 / Accepted: 19 December 2018 / Published: 21 December 2018
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Abstract
A multicenter pilot program for universal newborn screening of Sickle cell disease (SCD) was conducted in two centres of Northern Italy (Padova and Monza). High Performance Liquid Chromatography (HPLC) was performed as the first test on samples collected on Guthrie cards and molecular [...] Read more.
A multicenter pilot program for universal newborn screening of Sickle cell disease (SCD) was conducted in two centres of Northern Italy (Padova and Monza). High Performance Liquid Chromatography (HPLC) was performed as the first test on samples collected on Guthrie cards and molecular analysis of the β-globin gene (HBB) was the confirmatory test performed on the HPLC-positive or indeterminate samples. 5466 samples of newborns were evaluated. Of these, 5439/5466 were submitted to HPLC analysis and the molecular analysis always confirmed in all the alteration detected in HPLC (62/5439 newborns); 4/5439 (0.07%) were SCD affected, 37/5439 (0.68%) were HbAS carriers and 21/5439 (0.40%) showed other hemoglobinopathies. Stored dried blood spots were adequate for HPLC and β-globin gene molecular analysis. Samples were suitable for analysis until sixteen months old. A cut-off of A1 percentage, in order to avoid false negative or unnecessary confirmation tests, was identified. Our experience showed that several technical issues need to be addressed and resolved while developing a multicenter NBS program for SCD in a country where there is no national neonatal screening (NBS) program for SCD and NBS programs occur on a regional basis. Full article
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Open AccessArticle Neonatal Screening for Sickle Cell Disease in Belgium for More than 20 Years: An Experience for Comprehensive Care Improvement
Int. J. Neonatal Screen. 2018, 4(4), 37; https://doi.org/10.3390/ijns4040037
Received: 7 October 2018 / Revised: 15 November 2018 / Accepted: 20 November 2018 / Published: 27 November 2018
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Abstract
Our previous results reported that compared to sickle cell patients who were not screened at birth, those who benefited from it had a lower incidence of a first bacteremia and a reduced number and days of hospitalizations. In this context, this article reviews [...] Read more.
Our previous results reported that compared to sickle cell patients who were not screened at birth, those who benefited from it had a lower incidence of a first bacteremia and a reduced number and days of hospitalizations. In this context, this article reviews the Belgian experience on neonatal screening for sickle cell disease (SCD). It gives an update on the two regional neonatal screening programs for SCD in Belgium and their impact on initiatives to improve clinical care for sickle cell patients. Neonatal screening in Brussels and Liège Regions began in 1994 and 2002, respectively. Compiled results for the 2009 to 2017 period demonstrated a birth prevalence of sickle cell disorder above 1:2000. In parallel, to improve clinical care, (1) a committee of health care providers dedicated to non-malignant hematological diseases has been created within the Belgian Haematology Society; (2) a clinical registry was implemented in 2008 and has been updated in 2018; (3) a plan of action has been proposed to the Belgian national health authority. To date, neonatal screening is not integrated into the respective Belgian regional neonatal screening programs, the ongoing initiatives in Brussels and Liège Regions are not any further funded and better management of the disease through the implementation of specific actions is not yet perceived as a public health priority in Belgium. Full article
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Open AccessArticle Utilising the ‘Getting to Outcomes®’ Framework in Community Engagement for Development and Implementation of Sickle Cell Disease Newborn Screening in Kaduna State, Nigeria
Int. J. Neonatal Screen. 2018, 4(4), 33; https://doi.org/10.3390/ijns4040033
Received: 8 October 2018 / Revised: 6 November 2018 / Accepted: 11 November 2018 / Published: 16 November 2018
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Abstract
Background: Sickle Cell Disease (SCD) has been designated by WHO as a public health problem in sub-Saharan Africa, and the development of newborn screening (NBS) is crucial to the reduction of high SCD morbidity and mortality. Strategies from the field of implementation science [...] Read more.
Background: Sickle Cell Disease (SCD) has been designated by WHO as a public health problem in sub-Saharan Africa, and the development of newborn screening (NBS) is crucial to the reduction of high SCD morbidity and mortality. Strategies from the field of implementation science can be useful for supporting the translation of NBS evidence from high income countries to the unique cultural context of sub-Saharan Africa. One such strategy is community engagement at all levels of the healthcare system, and a widely-used implementation science framework, “Getting to Outcomes®” (GTO), which incorporates continuous multilevel evaluation by stakeholders about the quality of the implementation. Objectives: (1) to obtain critical information on potential barriers to NBS in the disparate ethnic groups and settings (rural and urban) in the healthcare system of Kaduna State in Nigeria; and, (2) to assist in the readiness assessment of Kaduna in the implementation of a sustainable NBS programme for SCD. Methods: Needs assessment was conducted with stakeholder focus groups for two days in Kaduna state, Nigeria, in November 2017. Results: The two-day focus group workshop had a total of 52 participants. Asking and answering the 10 GTO accountability questions provided a structured format to understand strengths and weaknesses in implementation. For example, we found a major communication gap between policy-makers and user groups. Conclusion: In a two-day community engagement workshop, stakeholders worked successfully together to address SCD issues, to engage with each other, to share knowledge, and to prepare to build NBS for SCD in the existing healthcare system. Full article

Review

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Open AccessReview Thalassemias: An Overview
Int. J. Neonatal Screen. 2019, 5(1), 16; https://doi.org/10.3390/ijns5010016
Received: 2 November 2018 / Revised: 12 March 2019 / Accepted: 18 March 2019 / Published: 20 March 2019
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Abstract
Thalassemia syndromes are among the most serious and common genetic conditions. They are indigenous in a wide but specific geographical area. However, through migration they are spreading across regions not previously affected. Thalassemias are caused by mutations in the α (HBA1/HBA2) [...] Read more.
Thalassemia syndromes are among the most serious and common genetic conditions. They are indigenous in a wide but specific geographical area. However, through migration they are spreading across regions not previously affected. Thalassemias are caused by mutations in the α (HBA1/HBA2) and β globin (HBB) genes and are usually inherited in an autosomal recessive manner. The corresponding proteins form the adult hemoglobin molecule (HbA) which is a heterotetramer of two α and two β globin chains. Thalassemia-causing mutations lead to an imbalanced globin chain production and consecutively to impaired erythropoiesis. The severity of the disease is largely determined by the degree of chain imbalance. In the worst case, survival is dependent on regular blood transfusions, which in turn cause transfusional iron overload and secondary multi-organ damage due to iron toxicity. A vigorous monitoring and treatment regime is required, even for the milder syndromes. Thalassemias are a major public health issue in many populations which many health authorities fail to address. Even though comprehensive care has resulted in long-term survival and good quality of life, poor access to essential components of management results in complications which increase the cost of treatment and lead to poor outcomes. These requirements are not recognized by measures such as the Global Burden of Disease project, which ranks thalassemia very low in terms of disability-adjusted life years (DALYs), and fails to consider that it ranks highly in the one to four-year-old age group, making it an important contributor to under-5 mortality. Thalassemia does not fulfil the criteria to be accepted as a target disease for neonatal screening. Nevertheless, depending on the screening methodology, severe cases of thalassemia will be detected in most neonatal screening programs for sickle cell disease. This is very valuable because: (1) it helps to prepare the affected families for having a sick child and (2) it is an important measure of secondary prevention. Full article
Open AccessReview Newborn Screening for Sickle Cell Disease in Europe
Int. J. Neonatal Screen. 2019, 5(1), 15; https://doi.org/10.3390/ijns5010015
Received: 30 December 2018 / Revised: 3 February 2019 / Accepted: 6 February 2019 / Published: 12 February 2019
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Abstract
The history of newborn screening (NBS) for sickle cell disease (SCD) in Europe goes back almost 40 years. However, most European countries have not established it to date. The European screening map is surprisingly heterogenous. The first countries to introduce sickle cell screening [...] Read more.
The history of newborn screening (NBS) for sickle cell disease (SCD) in Europe goes back almost 40 years. However, most European countries have not established it to date. The European screening map is surprisingly heterogenous. The first countries to introduce sickle cell screening on a national scale were France and England. The French West Indies started to screen their newborns for SCD as early as 1983/84. To this day, all countries of the United Kingdom of Great Britain and Northern Ireland have added SCD as a target disease to their NBS programs. The Netherlands, Spain and Malta also have national programs. Belgium screens regionally in the Brussels and Liège regions, Ireland has been running a pilot for many years that has become quasi-official. However, the Belgian and Irish programs are not publicly funded. Italy and Germany have completed several pilot studies but are still in the preparatory phase of national NBS programs for SCD, although both countries have well-established concepts for metabolic and endocrine disorders. This article will give a brief overview of the situation in Europe and put a focus on the programs of the two pioneers of the continent, England and France. Full article
Open AccessReview Improving Screening Programmes for Sickle Cell Disorders and Other Haemoglobinopathies in Europe: The Role of Patient Organisations
Int. J. Neonatal Screen. 2019, 5(1), 12; https://doi.org/10.3390/ijns5010012
Received: 31 December 2018 / Revised: 24 January 2019 / Accepted: 25 January 2019 / Published: 29 January 2019
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Abstract
This discussion paper has been written to show the unique contribution and added value that Patient Organisations can give to the development and improvement of newborn screening programmes for sickle cell disorder (SCD) and other haemoglobinopathies in Europe. As an example, the action [...] Read more.
This discussion paper has been written to show the unique contribution and added value that Patient Organisations can give to the development and improvement of newborn screening programmes for sickle cell disorder (SCD) and other haemoglobinopathies in Europe. As an example, the action of the Sickle Cell Society (SCS) in partnership with statutory organisations in the U.K., such as the National Health Service (NHS) Sickle Cell and Thalassaemia Screening Programme (NHS SCT SP), will be described. Full article
Open AccessReview The Neonatal Screening Program in Brazil, Focus on Sickle Cell Disease (SCD)
Int. J. Neonatal Screen. 2019, 5(1), 11; https://doi.org/10.3390/ijns5010011
Received: 28 September 2018 / Revised: 21 January 2019 / Accepted: 23 January 2019 / Published: 26 January 2019
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Abstract
Since 2001, the Brazilian Ministry of Health has been coordinating a National Neonatal Screening Program (NNSP) that now covers all the 26 states and the Federal District of the Brazilian Republic and targets six diseases including sickle cell disease (SCD) and other hemoglobinopathies. [...] Read more.
Since 2001, the Brazilian Ministry of Health has been coordinating a National Neonatal Screening Program (NNSP) that now covers all the 26 states and the Federal District of the Brazilian Republic and targets six diseases including sickle cell disease (SCD) and other hemoglobinopathies. In 2005, the program coverage reached 80% of the total live births. Since then, it has oscillated between 80% and 84% globally with disparities from one state to another (>95% in São Paulo State). The Ministry of Health has also published several Guidelines for clinical follow-up and treatment for the diseases comprised by the neonatal screening program. The main challenge was, and still is, to organize the public health network (SUS), from diagnosis and basic care to reference centers in order to provide comprehensive care for patients diagnosed by neonatal screening, especially for SCD patients. Considerable gains have already been achieved, including the implementation of a network within SUS and the addition of scientific and technological progress to treatment protocols. The goals for the care of SCD patients are the intensification of information provided to health care professionals and patients, measures to prevent complications, and care and health promotion, considering these patients in a global and integrated way, to reduce mortality and enhance their quality of life. Full article
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Open AccessReview Newborn Screening for Sickle Cell Disease and Other Hemoglobinopathies: A Short Review on Classical Laboratory Methods—Isoelectric Focusing, HPLC, and Capillary Electrophoresis
Int. J. Neonatal Screen. 2018, 4(4), 39; https://doi.org/10.3390/ijns4040039
Received: 30 September 2018 / Revised: 31 October 2018 / Accepted: 1 November 2018 / Published: 5 December 2018
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Abstract
Sickle cell disease (SCD) and other hemoglobinopathies are a major health concern with a high burden of disease worldwide. Since the implementation of newborn screening (NBS) for SCD and other hemoglobinopathies in several regions of the world, technical progress of laboratory methods was [...] Read more.
Sickle cell disease (SCD) and other hemoglobinopathies are a major health concern with a high burden of disease worldwide. Since the implementation of newborn screening (NBS) for SCD and other hemoglobinopathies in several regions of the world, technical progress of laboratory methods was achieved. This short review aims to summarize the current practice of classical laboratory methods for the detection of SCD and other hemoglobinopathies. This includes the newborn screening technologies of high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), and isoelectric focusing (IEF). Full article
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Open AccessReview Newborn Screening for SCD in the USA and Canada
Int. J. Neonatal Screen. 2018, 4(4), 36; https://doi.org/10.3390/ijns4040036
Received: 3 October 2018 / Revised: 19 November 2018 / Accepted: 20 November 2018 / Published: 26 November 2018
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Abstract
Sickle cell disease (SCD) encompasses a group of inherited red cell disorders characterized by an abnormal hemoglobin, Hb S. The most common forms of SCD in the United States and Canada are identified through universal newborn screening (NBS) programs. Now carried out in [...] Read more.
Sickle cell disease (SCD) encompasses a group of inherited red cell disorders characterized by an abnormal hemoglobin, Hb S. The most common forms of SCD in the United States and Canada are identified through universal newborn screening (NBS) programs. Now carried out in all fifty U.S. states and 8 Canadian provinces, NBS for SCD represents one of the major public health advances in North America. The current status of NBS programs for hemoglobinopathies and the screening techniques employed in many regions worldwide reflect in large part the U.S. and Canadian experiences. Although the structure, screening algorithms and laboratory procedures, as well as reporting and follow up, vary between NBS programs, the overall workflow is similar. The current review summarized the historical background, current approaches, and methods used to screen newborns for SCD in the United States and Canada. Full article
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Open AccessReview Newborn Sickle Cell Disease Screening Using Electrospray Tandem Mass Spectrometry
Int. J. Neonatal Screen. 2018, 4(4), 35; https://doi.org/10.3390/ijns4040035
Received: 7 September 2018 / Revised: 20 November 2018 / Accepted: 22 November 2018 / Published: 24 November 2018
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Abstract
There is a growing demand for newborn sickle cell disease screening globally. Historically techniques have relied on the separation of intact haemoglobin tetramers using electrophoretic or liquid chromatography techniques. These techniques also identify haemoglobin variants of no clinical significance. Specific electrospray ionization-mass spectrometry-mass [...] Read more.
There is a growing demand for newborn sickle cell disease screening globally. Historically techniques have relied on the separation of intact haemoglobin tetramers using electrophoretic or liquid chromatography techniques. These techniques also identify haemoglobin variants of no clinical significance. Specific electrospray ionization-mass spectrometry-mass spectrometry techniques to analyse targeted peptides formed after digestion of the haemoglobin with trypsin were reported in 2005. Since this time the method has been further developed and adopted in several European countries. It is estimated that more than one million babies have been screened with no false-negative cases reported. This review reports on the current use of the technique and reviews the related publications. Full article
Open AccessReview Point-of-Care Testing for G6PD Deficiency: Opportunities for Screening
Int. J. Neonatal Screen. 2018, 4(4), 34; https://doi.org/10.3390/ijns4040034
Received: 1 October 2018 / Revised: 13 November 2018 / Accepted: 14 November 2018 / Published: 19 November 2018
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Abstract
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked genetic disorder, is associated with increased risk of jaundice and kernicterus at birth. G6PD deficiency can manifest later in life as severe hemolysis, when the individual is exposed to oxidative agents that range from foods such as [...] Read more.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked genetic disorder, is associated with increased risk of jaundice and kernicterus at birth. G6PD deficiency can manifest later in life as severe hemolysis, when the individual is exposed to oxidative agents that range from foods such as fava beans, to diseases such as typhoid, to medications such as dapsone, to the curative drugs for Plasmodium (P.) vivax malaria, primaquine and tafenoquine. While routine testing at birth for G6PD deficiency is recommended by the World Health Organization for populations with greater than 5% prevalence of G6PD deficiency and to inform P. vivax case management using primaquine, testing coverage is extremely low. Test coverage is low due to the need to prioritize newborn interventions and the complexity of currently available G6PD tests, especially those used to inform malaria case management. More affordable, accurate, point-of-care (POC) tests for G6PD deficiency are emerging that create an opportunity to extend testing to populations that do not have access to high throughput screening services. Some of these tests are quantitative, which provides an opportunity to address the gender disparity created by the currently available POC qualitative tests that misclassify females with intermediate G6PD activity as normal. In populations where the epidemiology for G6PD deficiency and P. vivax overlap, screening for G6PD deficiency at birth to inform care of the newborn can also be used to inform malaria case management over their lifetime. Full article
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Open AccessReview Newborn Screening for Sickle Cell Disease: Indian Experience
Int. J. Neonatal Screen. 2018, 4(4), 31; https://doi.org/10.3390/ijns4040031
Received: 12 September 2018 / Revised: 5 November 2018 / Accepted: 7 November 2018 / Published: 13 November 2018
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Abstract
Sickle cell disease (SCD) is a major public health problem in India with the highest prevalence amongst the tribal and some non-tribal ethnic groups. The clinical manifestations are extremely variable ranging from a severe to mild or asymptomatic condition. Early diagnosis and providing [...] Read more.
Sickle cell disease (SCD) is a major public health problem in India with the highest prevalence amongst the tribal and some non-tribal ethnic groups. The clinical manifestations are extremely variable ranging from a severe to mild or asymptomatic condition. Early diagnosis and providing care is critical in SCD because of the possibility of lethal complications in early infancy in pre-symptomatic children. Since 2010, neonatal screening programs for SCD have been initiated in a few states of India. A total of 18,003 babies have been screened by automated HPLC using either cord blood samples or heel prick dried blood spots and 2944 and 300 babies were diagnosed as sickle cell carriers and SCD respectively. A follow up of the SCD babies showed considerable variation in the clinical presentation in different population groups, the disease being more severe among non-tribal babies. Around 30% of babies developed serious complications within the first 2 to 2.6 years of life. These pilot studies have demonstrated the feasibility of undertaking newborn screening programs for SCD even in rural areas. A longer follow up of these babies is required and it is important to establish a national newborn screening program for SCD in all of the states where the frequency of the sickle cell gene is very high followed by the development of comprehensive care centers along with counselling and treatment facilities. This comprehensive data will ultimately help us to understand the natural history of SCD in India and also help the Government to formulate strategies for the management and prevention of sickle cell disease in India. Full article
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