Refine Search

New Search

Results in Journal International Journal of Neonatal Screening: 244

(searched for: journal_id:(1713577))
Page of 5
Articles per Page
by
Show export options
  Select all
International Journal of Neonatal Screening, Volume 7; doi:10.3390/ijns7010006

Abstract:
Newborn screening (NBS) has widely been utilized in developed countries as a cost-effective public health strategy that reduces morbidity and mortality. Developing countries, however, are new to the NBS scene and have their own unique challenges, both in instituting the program as well as effectively acting on the results. NBS offers numerous ethical issues on a global scale, however, here we argue that there are unique ethical issues surrounding the development and expansion of newborn screening in Latin America given its highly heterogenous population. Once a NBS program is effectively instated, ethical considerations continue when pursuing expansion of screening to include further conditions. While Latin America grapples with the ethics of expanded newborn screening (ENBS), some developed countries discuss utility of genomic sequencing technologies in the newborn population. When the ability to detect further pathology is expanded, one must know what to do with this information. As rare diseases are identified either on ENBS or via genome sequencing, access to treatments for these rare diseases can be a real challenge. If we consider newborn screening as a global initiative, then we need more than a deontology approach to analyze these challenges; we need an approach that considers the unique characteristics of each territory and tremendous heterogeneity that exists prior to the implementation of these programs. As genomic technology advances further in the developed world, while some developing countries still lack even basic newborn screening, there is a further widening of the gap in global health disparities. The question is posed as to who has responsibility for these newborns’ lives on an international level. Without an approach towards newborn screening that accounts for the diverse global population, we believe optimal outcomes for newborns and families across the world will not be achieved.
International Journal of Neonatal Screening, Volume 7; doi:10.3390/ijns7010005

Abstract:
Routine newborn screening for many disorders is now so ingrained in newborn care that there is no question about whether it should be done. However, acceptance of newborn screening was not guaranteed when Robert Guthrie introduced it for phenylketonuria (PKU). This article describes the professional and personal story of Guthrie, a physician and microbiologist, who veered from cancer research to a commitment to prevent intellectual disability from PKU. It recounts how Guthrie was able to overcome strong opposition to mandatory screening from prominent physicians and medical societies, so that newborn screening for PKU would be routinely performed throughout the developed world, and would eventually form the basis for the (much more) comprehensive screening conducted today.
International Journal of Neonatal Screening, Volume 7; doi:10.3390/ijns7010004

Abstract:
Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that International Journal of Neonatal Screening maintains its standards for the high quality of its published papers
International Journal of Neonatal Screening, Volume 7; doi:10.3390/ijns7010002

Abstract:
The potential for genomic screening of the newborn, specifically adding genomic screening to current newborn screening (NBS), raises very significant ethical issues. Regardless of whether NBS of this type would include entire genomes or only the coding region of the genome (exome screening) or even sequencing specific genes, the ethical issues raised would be enormous. These issues include the limitations of bioinformatic interpretation of identified variants in terms of pathogenicity and accurate prognosis, the potential for substantial uncertainty about appropriate diagnosis, therapy, and follow-up, the possibility of much anxiety among providers and parents, the potential for unnecessary treatment and “medicalizing” normal children, the possibility of adding large medical costs for otherwise unnecessary follow-up and testing, the potential for negatively impacting medical and life insurance, and the almost impossible task of obtaining truly-informed consent. Moreover, the potentially-negative consequences of adding genomic sequencing to NBS might jeopardize all of NBS which has been and continues to be so beneficial for thousands of children and their families throughout the world.
International Journal of Neonatal Screening, Volume 7; doi:10.3390/ijns7010003

Abstract:
It would be difficult to overestimate the importance of persistent, thoughtful parents and their importance in the development of treatments for their children’s rare disorders. Almost a century ago in Norway, observant parents led a brilliant young physician-scientist to his discovery of the underlying cause of their children’s profound developmental delay—i.e., phenylketonuria, or PKU. Decades later, in a recovering war-ravaged Britain, an equally persistent mother pressed the scientists at Birmingham Children’s Hospital to find a way to treat her seriously damaged daughter, Sheila, who suffered from PKU. Living on the financial edge, this mother insisted that Bickel and colleagues develop such a diet, and she volunteered Sheila to be the patient in the trial. The scientists concluded that the low phenylalanine diet helped but needed to be started very early—so, newborn screening was born to permit the implementation of this. Many steps brought us to where we are today, but these courageous parents made it all begin.
International Journal of Neonatal Screening, Volume 7; doi:10.3390/ijns7010001

Abstract:
Newborn screening (NBS) for Cystic Fibrosis (CF) has revolutionized the diagnosis of this inherited disease. CF NBS goals are to identify, diagnose, and initiate early CF treatment to attain better health outcomes. Abnormal CF NBS infants require diagnostic analysis via sweat chloride testing (ST). During ST, insufficient sweat volume collection causes a “quantity not sufficient” (QNS) test result and may delay CF diagnosis. The CF Foundation recommends QNS rates
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040096

Abstract:
Pompe disease (GSD II) is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme acid-α-glucosidase (GAA, EC 3.2.1.20), leading to generalized accumulation of lysosomal glycogen especially in the heart, skeletal, and smooth muscle, and the nervous system. It is generally classified based on the age of onset as infantile (IOPD) presenting during the first year of life, and late onset (LOPD) when it presents afterwards. In our study, a cohort of 13,627 samples were tested between January 2017 and December 2018 for acid-α-glucosidase (GAA, EC 3.2.1.20) deficiency either by fluorometry or tandem mass spectrometry (MS). Testing was performed for patients who displayed conditions of unknown etiology, e.g., CK elevations or cardiomyopathy, in the case of infantile patients. On average 8% of samples showed activity below the reference range and were further assessed by another enzyme activity measurement or molecular genetic analysis. Pre-analytical conditions, like proper drying, greatly affect enzyme activity, and should be assessed with measurement of reference enzyme(s). In conclusion, at-risk testing can provide a good first step for the future introduction of newborn screening for Pompe disease. It yields immediate benefits for the patients regarding the availability and timeliness of the diagnosis. In addition, the laboratory can introduce the required methodology and gain insights in the evaluation of results in a lower throughput environment. Finally, awareness of such a rare condition is increased tremendously among local physicians which can aid in the introduction newborn screening.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040095

Abstract:
Newborn Bloodspot Screening (NBS) has existed for over 60 years, having been initiated by Guthrie in the U.S. In the Philippines, NBS was introduced in 1996 and later was supported by legislation. The NBS program now includes 29 conditions, covering 91.6% of the newborn population in 2019. Program growth and expansion necessitated development of a formal performance evaluation and assessment scheme (PEAS) for monitoring performance and for continuously improving quality. This study’s objective was to present the development, implementation, and results to date of the Philippine Performance PEAS (PPEAS). Using the comprehensive listing of laboratory and non-laboratory elements in the model PEAS system in the U.S., PPEAS tools were developed for critical Philippine NBS system components: regional Department of Health (national health agency, Philippines) (DOH) offices (CHDs), NBS laboratories (NSCs), NBS specimen submitters (NSFs), and long-term case management centers (NBSCCs). Data generated from the various PPEAS have been periodically reviewed and analyzed for NBS system impact. PPEAS were developed to facilitate quality improvement at various levels of the Philippine NBS system. PPEAS identified successes, gaps, and challenges to be addressed by NSCs, NSFs, CHDs, and NBSCCs with the assistance of the Newborn Screening Reference Center and the Department of Health.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040094

Abstract:
Introduction: Cost-effectiveness (CEA) and cost–utility analyses (CUA) have become popular types of economic evaluations (EE) used for evidence-based decision-making in healthcare resource allocation. Newborn screening programs (NBS) can have significant clinical benefits for society, and cost-effectiveness analysis may help to select the optimal strategy among different screening programs, including the no-screening option, on different conditions. These economic analyses of NBS, however, are hindered by several methodological challenges. This study explored the methodological quality in recent NBS economic evaluations and analyzed the main challenges and strategies adopted by researchers to deal with them. Methods: A scoping review was conducted according to PRISMA methodology to identify CEAs and CUAs of NBS. The methodological quality of the retrieved studies was assessed quantitatively using a specific guideline for the quality assessment of NBS economic evaluations, by calculating a general score for each EE. Challenges in the studies were then explored using thematic analysis as a qualitative synthesis approach. Results: Thirty-five studies met the inclusion criteria. The quantitative analysis showed that the methodological quality of NBS economic evaluations was heterogeneous. Lack of clear description of items related to results, discussion, and discounting were the most frequent flaws. Methodological challenges in performing EEs of neonatal screenings include the adoption of a long time horizon, the use of quality-adjusted life years as health outcome measure, and the assessment of costs beyond the screening interventions. Conclusions: The results of this review can support future economic evaluation research, aiding researchers to develop a methodological guidance to perform EEs aimed at producing solid results to inform decisions for resource allocation in neonatal screening.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040093

Abstract:
Glutaric aciduria type 1, homocystinuria, isovaleric acidaemia, long-chain hydroxyacyl CoA dehydrogenase deficiency and maple syrup urine disease are all inborn errors of metabolism that can be detected through newborn bloodspot screening. This evaluation was undertaken in 2013 to provide evidence to the UK National Screening Committee for the cost-effectiveness of including these five conditions in the UK Newborn Bloodspot Screening Programme. A decision-tree model with lifetable estimates of outcomes was built with the model structure and parameterisation informed by a systematic review and expert clinical judgment. A National Health Service/Personal Social Services perspective was used, and lifetime costs and quality-adjusted life years (QALYs) were discounted at 1.5%. Uncertainty in the results was explored using expected value of perfect information analysis methods together with a sensitivity analysis using the screened incidence rate in the UK from 2014 to 2018. The model estimates that screening for all the conditions is more effective and cost saving when compared to not screening for each of the conditions, and the results were robust to the updated incidence rates. The key uncertainties included the sensitivity and specificity of the screening test and the estimated costs and QALYs.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040091

Abstract:
There have been significant advances allowing for the integration of mucopolysaccharidosis I into newborn screening programs. Initial experiences using a single-tier approach for this disorder have highlighted shortcomings that require immediate remediation. The recent evaluation of a second-tier biomarker integrated into the MPS I newborn screening protocol has been demonstrated to greatly improve the precision and predictive value of newborn screening for this disorder. This commentary urges newborn screening programs to learn from these experiences and improve newborn screening for mucopolysaccharidosis I and future mucopolysaccharidoses newborn screening programs by implementation of a second-tier biomarker analyte.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040092

Abstract:
In 2015, the newborn screening (NBS) programmes in England and Wales were expanded to include four additional disorders: Classical Homocystinuria, Isovaleric Acidemia, Glutaric Aciduria Type 1 and Maple Syrup Urine Disease, bringing the total number of analytes quantified to eight: phenylalanine, tyrosine, leucine, methionine, isovalerylcarnitine, glutarylcarnitine, octanoylcarnitine and decanoylcarnitine. Post-implementation, population data monitoring showed that inter-laboratory variation was greater than expected, with 90th centiles varying from 17 to 59%. We evaluated the effect of stable isotope internal standard (IS) used for quantitation on inter-laboratory variation. Four laboratories analysed routine screening samples (n > 101,820) using a common IS. Inter-laboratory variation was determined for the eight analytes and compared with results obtained using an in-house common IS (n > 102,194). A linear mixed-effects model was fitted to the data. Using a common IS mix reduced the inter-laboratory variation significantly (p < 0.05) for five analytes. For three analytes, the lack of significance was explained by use of individual laboratory “calibration factors”. For screening programmes where laboratories adhere to single analyte cut-off values (COVs), it is important that inter-laboratory variation is minimised, primarily to prevent false positive results. Whilst the use of a common IS helps achieve this, it is evident that instrument set-up also contributes to inter-laboratory variation.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040089

Abstract:
Pennsylvania started newborn screening for Pompe disease in February 2016. Between February 2016 and December 2019, 531,139 newborns were screened. Alpha-Glucosidase (GAA) enzyme activity is measured by flow-injection tandem mass spectrometry (FIA/MS/MS) and full sequencing of the GAA gene is performed as a second-tier test in all newborns with low GAA enzyme activity [
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040090

Abstract:
Newborn screening enables the diagnosis of treatable disorders at the early stages, and because of its countless benefits, conditions have been continuously added to screening panels, allowing early intervention, aiming for the prevention of irreversible manifestations and even premature death. Mucopolysaccharidoses (MPS) are lysosomal storage disorders than can benefit from an early diagnosis, and thus are being recommended for newborn screening. They are multisystemic progressive disorders, with treatment options already available for several MPS types. MPS I was the first MPS disorder enrolled in the newborn screening (NBS) panel in the USA and a few other countries, and other MPS types are expected to be added. Very few studies about NBS for MPS in Latin America have been published so far. In this review, we report the results of pilot studies performed in Mexico and Brazil using different methodologies: tandem mass spectrometry, molecular analysis, digital microfluidics, and fluorimetry. These experiences are important to report and discuss, as we expect to have several MPS types added to NBS panels shortly. This addition will enable timely diagnosis of MPS, avoiding the long diagnostic odyssey that is part of the current natural history of this group of diseases, and leading to a better outcome for the affected patients.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040088

Abstract:
The lysosomal storage disorder, mucopolysaccharidosis I (MPSI), results from mutations in IDUA, the gene that encodes the glycosaminoglycan-degrading enzyme α-L-iduronidase. Newborn screening efforts for MPSI have greatly increased the number of novel IDUA variants identified, but with insufficient experimental evidence regarding their pathogenicity, many of these variants remain classified as variants of uncertain significance (VUS). Defining pathogenicity for novel IDUA variants is critical for decisions regarding medical management and early intervention. Here, we describe a biochemical platform for the characterization of IDUA variants that relies on viral delivery of IDUA DNA into IDUA-deficient HAP1 cells and isolation of single cell expression clones. The relative specific activity of wild-type and variant α-iduronidase was determined using a combination of Western blot analysis and α-iduronidase activity assays. The specific activity of each variant enzyme was consistent across different single cell clones despite variable IDUA expression and could be accurately determined down to 0.05–0.01% of WT α-iduronidase activity. With this strategy we compared the specific activities of known pseudodeficiency variants (p.His82Gln, p.Ala79Thr, p.Val322Glu, p.Asp223Asn) or pathogenic variants (p.Ser633Leu, p.His240Arg) with variants of uncertain significance (p.Ser586Phe, p.Ile272Leu). The p.Ser633Leu and p.His240Arg variants both show very low activities consistent with their association with Scheie syndrome. In our experiments, however, p.His240Arg exhibited a specific activity five times higher than p.Ser633Leu in contrast to other reports showing equivalent activity. Cell clones expressing the p.Ser586Phe and p.Ile272Leu variants had specific activities in the range of other pseudodeficiency variants tested. Our findings show that pseudodeficiency and pathogenic variants can be distinguished from each other with regard to specific activity, and confirms that all the pseudodeficiency variants variably reduce α-iduronidase activity. We envision this platform will be a valuable resource for the rigorous assessment of the novel IDUA variants emerging from the expansion of newborn screening efforts.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040087

Abstract:
To tackle the ever-increasing ambitions of the International Journal of Neonatal Screening (IJNS), in November 2019, we were looking for an Associate Editor to strengthen the Editorial board of IJNS
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040086

Abstract:
It is with great sadness that we have to inform you of the passing on 13 August 2020, of Dr
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040085

Abstract:
Mucopolysaccharidosis type I (MPS I) is a progressive lysosomal storage disease, with neurological and visceral involvement, in which early diagnosis through newborn screening (NBS) and early treatment can improve outcomes. We present our first 5 years of experience with laboratory and clinical management of NBS for MPS I. Since 2015, we have screened 160,011 newborns by measuring α-L-iduronidase (IDUA) activity and, since 2019, glycosaminoglycans (GAGs) in dried blood spot (DBS) as a second-tier test. Positive screening patients were referred to our clinic for confirmatory clinical and molecular testing. We found two patients affected by MPS I (incidence of 1:80,005). Before the introduction of second-tier testing, we found a high rate of false-positives due to pseudodeficiency. With GAG analysis in DBS as a second-tier test, no false-positive newborns were referred to our clinic. The confirmed patients were early treated with enzyme replacement therapy and bone-marrow transplantation. For both, the clinical outcome of the disease is in the normal range. Our experience confirms that NBS for MPS I is feasible and effective, along with the need to include GAG assay as a second-tier test. Follow-up of the two positive cases identified confirms the importance of early diagnosis through NBS and early treatment to improve the outcome of these patients.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040083

Abstract:
Stored dried blood spots (DBS) can provide valuable samples for the retrospective diagnosis of inborn errors of metabolism, and for validation studies for newborn blood spot screening programs. Acylcarnitine species are subject to degradation upon long-term storage at room temperature, but limited data are available on the stability in original samples and the impact on acylcarnitine ratios. We analysed complete acylcarnitine profiles by flow-injection tandem mass spectrometry in 598 anonymous DBS stored from 2013 to 2017, at +4 °C during the first year and thereafter at room temperature. The concentrations of C2-, C3-, C4-, C5-, C6-, C8-, C10:1-, C10-, C12:1-, C12-, C14:1-, C14-, C16:1-, C16-, C18:2-, C18:1-, C18-, C5OH+C4DC-, C18:1OH-, and C16DC-carnitine decreased significantly, whereas a positive trend was found for free carnitine. Only the C4/C8-, C8/C10-, C14:1/C10- and C14:1/C16-carnitine ratios appeared robust for the metabolite instability. The metabolite instability may provoke the wrong interpretation of test results in the case of retrospective studies and risk the inaccurate estimation of cut-off targets in validation studies when only stored control DBS are used. We recommend including control DBS in diagnostic, retrospective cohort studies, and, for validation studies, we recommend using fresh samples and repeatedly re-evaluating cut-off targets.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040084

Abstract:
The expansion of national newborn screening (NBS) programmes has provided significant benefits in the diagnosis and early treatment of several rare, heritable conditions, preventing adverse health outcomes for most affected infants. New technological developments have enabled the implementation of testing panel covering over 50 disorders. Consequently, the increment of false positive rate has led to a high number of healthy infants recalled for expensive and often invasive additional testing, opening a debate about the harm-benefit ratio of the expanded newborn screening. The false-positive rate represents a challenge for healthcare providers working in NBS systems. Here, we give an overview on the most commonly used strategies for decreasing the adverse effects due to inconclusive screening results. The focus is on NBS performance improvement through the implementation of analytical methods, the application of new and more informative biomarkers, and by using post-analytical interpretive tools. These strategies, used as part of the NBS process, can to enhance the positive predictive value of the test and reduce the parental anxiety and healthcare costs related to the unnecessary tests and procedures.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040082

Abstract:
Generalizing about the cost-effectiveness of newborn screening (NBS) is difficult due to the heterogeneity of disorders included in NBS panels, along with data limitations. Furthermore, it is unclear to what extent evidence about cost-effectiveness should influence decisions to screen for specific disorders. Screening newborns for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can serve as a useful test case, since there is no global consensus on whether CAH should be part of NBS panels. Published and unpublished cost-effectiveness analyses of CAH screening have yielded mixed findings, largely due to differences in methods and data sources for estimating health outcomes and associated costs of early versus late diagnosis as well as between-country differences. Understanding these methodological challenges can help inform future analyses and could also help interested policymakers interpret the results of economic evaluations.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040081

Abstract:
We screened 51,081 newborns for X-linked adrenoleukodystrophy (ALD) using a two-tiered strategy quantifying very long chain lysophosphatadylcholines (LPC). Our testing strategy used flow injection tandem mass spectrometry for the first-tier analysis of LPCs, and second-tier quantification of C26:0 LPC using liquid chromatography tandem mass spectrometry. There were 364 specimens considered abnormal using our first-tier algorithm that relied on the four LPC measurements and post-analytical tools. Second-tier test results were reported as normal or abnormal based on a cutoff for the single analyte, C26:0 LPC. Eleven cases were reported as abnormal based on second-tier test results. One male with ALD was identified, and two females with peroxisomal biogenesis disorders were also identified. A single female case remains unresolved, due to a loss to follow up after a negative molecular test result for ABCD1 gene sequencing. The positive predictive value for confirmed, clinically relevant disorders during this pilot study was 27.3%. Challenges identified during the study period were based around coverage for confirmatory testing, particularly if family members needed molecular testing, which is an ongoing issue with newborn screening in Georgia. We also encountered issues with the follow up for a patient who remained asymptomatic. Due to the different timelines involved with clinical findings in ALD, follow-up coordination may be more difficult, particularly if the child identified by newborn screening (NBS) is the only member of the family affected, or able to be tested.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040080

Abstract:
As biotechnologies advance and better treatment regimens emerge, there is a trend toward applying more advanced technologies and adding more conditions to the newborn screening (NBS) panel. In the current Recommended Uniform Screening Panel (RUSP), all conditions but one, congenital hypothyroidism, have well-defined genes and inheritance patterns, so it is beneficial to incorporate molecular testing in NBS when it is necessary and appropriate. Indeed, the applications of molecular technologies have taken NBS to previously uncharted territory. In this paper, based on our own program experience and what has been reported in the literature, we describe current practices regarding the applications of molecular technologies in routine NBS practice in the era of genomic and precision medicine.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040079

Abstract:
Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome, is a lysosomal storage disorder (LSD) caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). MPS II satisfies all criteria defined by the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) for inclusion in the Recommended Uniform Screening Panel (RUSP) for newborn screening, apart from the fact that only minimal prospective population screening data are available. This report details the analytical validation, clinical validation, and implementation of a fluorometric assay for measurement of IDS activity in newborn dried blood spot (DBS) specimens at the Missouri State Public Health Laboratory (MSPHL). The assay is performed in a microwell plate format requiring approximately 15 min of hands-on time per plate and an incubation time of two hours. The analytical validation of this assay included linearity, analytical sensitivity, precision, and carry-over testing. Clinical validation was completed using more than 5000 deidentified presumptive normal newborn DBS specimens as well as seven specimens from patients known to be affected with MPS II. Following validation, MSPHL began prospective screening using the IDS assay on 1 November 2018. In the first 18 months of screening (to 30 June 2020), 146,954 specimens were prospectively screened using the method. Two newborns were identified with severe Hunter syndrome and the assay had a presumptive positive rate of 0.022%.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040077

Abstract:
Proximal urea cycle disorders (PUCDs) have adverse outcomes such as intellectual disability and death, which may benefit from newborn screening (NBS) through early detection and prevention with early treatment. Ornithine transcarbamylase deficiency (OTCD) and carbamoyl phosphate synthetase 1 deficiency (CPS1D) are screened in six and eight states in the United States. We analyzed current evidence to see if it supports inclusion of PUCDs in the NBS panels based upon prevention potential, medical, diagnostic, treatment, and public health rationales. A literature review was performed in PubMed using MESH terms for OTCD, CPS1D, and NAGSD. A systematic review was performed in the hallmark of NBS inclusion criteria. We reviewed 31 articles. Molecular and biochemical diagnosis is available to provide diagnostic evidence. Untreated PUCDs have a significant burden with considerable developmental delay and mortality that may improve with early treatment. Tandem mass spectrometry can be used for NBS for PUCDs; however, citrulline and glutamine alone are not specific. Medical treatments currently available for PUCDs meet existing medical, diagnostic, treatment, and public health rationales. Improvement in NBS algorithms to increase sensitivity and specificity will allow earlier diagnosis and treatment to potentially improve disability and mortality rates.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040078

Abstract:
Newborn screening (NBS) for mucopolysaccharidosis type I (MPS I, Hurler syndrome) is currently conducted in about two-fifths of the NBS programs in the United States and in a few other countries. Screening is performed by measurement of residual activity of the enzyme alpha-l-iduronidase in dried blood spots using either tandem mass spectrometry or digital microfluidic fluorometry (DMF). In this article, we focus on the development and practical experience of using DMF to screen for MPS I in the USA. By means of their responses to a questionnaire, we determined for each responding program that is screening for MPS I using DMF the screen positive rate, follow-up methods, and classification of confirmed cases as either severe or attenuated. Overall, the results show that at the time of reporting, over 1.3 million newborns in the US were screened for MPS I using DMF, 2094 (0.173%) of whom were screen positive. Of these, severe MPS I was confirmed in five cases, attenuated MPS I was confirmed in two cases, and undetermined phenotype was reported in one case. We conclude that DMF is an effective and economical method to screen for MPS I and recommend second-tier testing owing to high screen positive rates. Preliminary results of NBS for MPS II and MPS III using DMF are discussed.
Published: 25 September 2020
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6040076

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 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.
Published: 17 September 2020
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030075

Abstract:
Newborn screening (NBS) laboratories cannot accurately compare mass spectrometry-derived results and cutoff values due to differences in testing methodologies. The objective of this study was to assess harmonization of laboratory proficiency test (PT) results using quality control (QC) data. Newborn Screening Quality Assurance Program (NSQAP) QC and PT data reported from 302 laboratories in 2019 were used to compare results among laboratories. QC materials were provided as dried blood spot cards which included a base pool and the base pool enriched with specific concentrations of metabolites in a linear range. QC data reported by laboratories were regressed on QC data reported by the Centers for Disease Control and Prevention (CDC), and laboratory’s regression parameters were used to harmonize their PT result. In general, harmonization tended to reduce overall variation in PT data across laboratories. The metabolites glutarylcarnitine (C5DC), tyrosine, and phenylalanine were displayed to highlight inter- and intra-method variability in NBS results. Several limitations were identified using retrospective data for harmonization, and future studies will address these limitations to further assess feasibility of using NSQAP QC data to harmonize PT data. Harmonizing NBS data using common QC materials appears promising to aid result comparison between laboratories.
Published: 15 September 2020
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030074

Abstract:
Newborn screening for critical congenital heart disease (CCHD) is recommended for implementation in many developed countries as the standard of care. Efforts to implement this point of care screen in developing regions face unique barriers, and present important opportunities. The First Pan-African Newborn Screening Conference, held in Rabat in June 2019, incorporated a workshop dedicated specifically to identifying and discussing CCHD screening issues in the Middle East Northern Africa (MENA) region. The issues explored may be beneficial as part of the greater discussion of CCHD screening’s growing importance in developing regions around the world. Screening experts presented education and lessons learned from previous CCHD implementations, including a hands-on technical demonstration of CCHD screening. Children’s HeartLink, The Newborn Foundation, and Children’s National Hospital each presented on their experiences working with teams and pilot projects from around the world. Experience in implementation from Children’s Hospital Marrakesh was presented and highlighted some of the unique findings, challenges, and experiences of screening in Morocco. As developing regions investigate the implementation of CCHD screening using pulse oximetry either as part of research studies, pilots, regional studies, or as part of a nationally supported program, data to inform policymakers on the benefits of screening and specific needs for infrastructure development and resources are essential. This special issue contains initial lessons learned on newborn CCHD screening from a select number of developing countries, including Saudi Arabia and Morocco and regions such as Latin America.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030073

Abstract:
Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare, progressive multisystemic lysosomal storage disorder with significant morbidity and premature mortality. Infants with MPS II develop signs and symptoms of the disorder in the early years of life, yet diagnostic delays are very common. Enzyme replacement therapy is an effective treatment option. It has been shown to prolong survival and improve or stabilize many somatic manifestations of the disorder. Our initial experience with newborn screening in 162,000 infants was previously reported. Here, we update that experience with the findings in 339,269 infants. Measurement of iduronate-2-sulfatase (I2S) activity was performed on dried blood spot samples submitted for other newborn screening disorders. A positive screen was defined as I2S activity less than or equal to 10% of the daily median. In this series, 28 infants had a positive screening test result, and four other infants had a borderline result. Three positive diagnoses of MPS II were established, and 25 were diagnosed as having I2S pseudodeficiency. The natural history and the clinical features of MPS II make it an ideal target for newborn screening. Newborn screening was effective in identifying affected infants in our population with an acceptable rate of false positive results.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030072

Abstract:
Two lysosomal storage disorders (LSDs), Pompe disease and Mucopolysaccharidosis type I (MPSI) were added to the Recommended Uniform Screening Panel (RUSP) for newborn screening (NBS) in 2015 and 2016, respectively. These conditions are being screened with variable practice in terms of primary and reflex analytes (either biochemical or molecular testing) as well as collection of short- and long-term follow-up elements. The goal of this study is to evaluate practices of state health departments in regards to screening methods and follow-up data collected. We conducted online surveys and phone questionnaires to determine each U.S. state’s practices for screening and follow-up of positive newborn screens. We report the first snapshot of practices for NBS for the LSDs included on the RUSP. All 50 U.S. states responded to our survey. The majority of U.S. states are not currently screening for Pompe disease and MPSI as of March 2020, but this number will increase to 38 states in the coming 1–3 years based on survey results. Our survey identifies data elements used by state health departments for short-and long-term follow-up that could serve as the basis of common elements for larger, public health-based analyses of the benefits and efficacy of screening for Pompe disease and MPSI.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030071

Abstract:
Congenital adrenal hyperplasia (CAH) was the fourth disorder added to the national Swedish neonatal screening program in 1986, and approximately 115,000 newborns are screened annually. Dried blood spot (DBS) screening with measurement of 17-hydroxyprogesterone (17OHP) is also offered to older children moving to Sweden from countries lacking a national DBS screening program. Here, we report an update on the CAH screening from January 2011 until December 2019. Results: During the study period, 1,030,409 newborns and 34,713 older children were screened. In total, 87 newborns were verified to have CAH, which gives an overall positive predictive value (PPV) of 11% and 21% for term infants. Including the five missed CAH cases identified during this period, this gives an incidence of 1:11,200 of CAH in Sweden. Among the older children, 12 of 14 recalled cases were found to be true positive for CAH. All patients were genotyped as part of the clinical follow-up and 70% of the newborns had salt wasting (SW) CAH and 92% had classic CAH (i.e., SW and simple virilizing (SV) CAH). In the group of 12 older children, none had SW CAH and two had SV CAH. Conclusion: The incidence of classic CAH is relatively high in Sweden. Early genetic confirmation with CYP21A2 genotyping has been a valuable complement to the analysis of 17OHP to predict disease severity, make treatment decisions and for the follow-up and evaluation of the screening program.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030070

Abstract:
Congenital adrenal hyperplasia (CAH) is a common treatable disorder which is associated with life-threatening adrenal crisis, sexual ambiguity, and/or abnormal growth if undiagnosed. Newborn screening is a cost-effective tool to detect affected babies early after birth to optimize their treatment and follow-up. Newborn screening however is in its nascent stage in India where it is not yet introduced universally for all babies. The following review briefly highlights the challenges (e.g., lack of universal screening, healthcare resources) and opportunities (e.g., reduction in morbidity and early correct gender assignment in females) associated with newborn screening for CAH in a large Indian birth cohort.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030068

Abstract:
Neonatal screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency is now performed in an increasing number of countries all over the world. The main goal of the screening is to achieve early diagnosis and treatment in order to prevent neonatal salt-crisis and death. The screening laboratory can also play an important role in increasing the general awareness of the disease and act as the source of information and education for clinicians to facilitate improved initial care, ensure prompt and correct glucocorticoid dosing to optimize the long-term outcome for the patients. A National CAH Registry and CYP21A2 genotyping provide valuable information both for evaluating the screening program and the clinical outcome. The Swedish experience is described.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030069

Abstract:
All newborn screening (NBS) for mucopolysaccharidosis-I (MPS-I) is carried out by the measurement of α-iduronidase (IDUA) enzymatic activity in dried blood spots (DBS). The majority of low enzyme results are due to pseudodeficiencies, and studies from the Mayo Clinic have shown that the false positive rate can be greatly reduced by including a second-tier analysis of glycosaminoglycans (GAGs) in DBS as part of NBS. In the present study, we obtained newborn DBS from 13 patients with severe MPS-I and 2 with attenuated phenotypes. These samples were submitted to four different GAG mass spectrometry analyses in a comparative study: (1) internal disaccharide; (2) endogenous disaccharide; (3) Sensi-Pro; (4) Sensi-Pro Lite (a variation of Sensi-Pro with a simplified workflow). Patients with attenuated MPS-I show less GAG elevation than those with severe disease, and all MPS-I patients were separated from the reference range using all four methods. The minimal differential factor (lowest GAG marker level in MPS-I samples divided by highest level in the reference range of 30 random newborns) was about two for internal disaccharide, Sensi-Pro, and Sensi-Pro Lite methods. The endogenous disaccharide was clearly the best method with a minimal differential of 16-fold. This study supports use of second-tier GAG analysis of newborn DBS, especially the endogenous disaccharide method, as part of NBS to reduce the false positive rate.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030067

Abstract:
Newborn screening for 21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia, has been performed routinely in the United States and other countries for over 20 years. Screening provides the opportunity for early detection and treatment of patients with 21OHD, preventing salt-wasting crisis during the first weeks of life. However, current first-tier screening methodologies lack specificity, leading to a large number of false positive cases, and adequate sensitivity to detect all cases of classic 21OHD that would benefit from treatment. This review summarizes the pathology of 21OHD and also the key stages of fetal hypothalamic-pituitary-adrenal axis development and adrenal steroidogenesis that contribute to limitations in screening accuracy. Factors leading to both false positive and false negative results are highlighted, along with specimen collection best practices used by laboratories in the United States and worldwide. This comprehensive review provides context and insight into the limitations of newborn screening for 21OHD for laboratorians, primary care physicians, and endocrinologists.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030066

Abstract:
Newborn screening (NBS) for Krabbe disease (KD) is currently underway in eight states in the USA, and there is continued discussion of whether to implement KD NBS in additional states. Workgroup members sought to survey a large number of families affected by KD. Families in KD and leukodystrophy family registries were contacted to seek their participation in The Krabbe Newborn Screening—Family Perspective Survey. The 170 respondents are comprised of the following: 138 family members with a KD individual diagnosed after development of symptoms, 20 notified about KD via NBS, and 12 with a KD individual diagnosed through family history of KD. The key results are that all NBS families with an early-infantile KD family member elected to pursue hematopoietic stem cell transplantation therapy. Of the 170 responders, 165 supported the implementation of KD NBS in all states in the USA.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030065

Abstract:
New York uses a two-tier assay to screen newborns for Krabbe disease and Pompe disease. Individual enzyme activities are measured in the first-tier, and specimens from newborns with low activity are reflexed to second tier Sanger sequencing of the associated gene. Using only this two-tiered approach, the screen positive and false positive rates were high. In this study, we added an additional step that examines the activity of four additional lysosomal enzymes. Results for all enzymes are integrated using the multivariate pattern recognition software called Collaborative Laboratory Integrated Reports (CLIR) to assess the risk for disease. Results after one year of screening using the new algorithm are compared to the prior year of screening without consideration of the additional enzymes and use of CLIR. With CLIR the number of babies referred for Krabbe disease was reduced by almost 80% (from 48 to 10) and the number of babies referred for Pompe disease was reduced by almost 32% (22 to 15).
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030064

Abstract:
Newborn screening (NBS) is a state-based public health program that aims to identify newborns at risk of certain disorders in the first days after birth to prevent permanent disability or death. Disorders on the Health and Human Services Federal Advisory Committee’s Recommended Uniform Screening Panel (RUSP) have been adopted by most state NBS programs; however, each state mandates specific disorders to be screened and implements their own system processes. Congenital adrenal hyperplasia (CAH) was added to the RUSP in 2005, and currently all 53 NBS programs universally screen for it. This paper provides a landscape of CAH screening in the United States, utilizing data voluntarily entered by state NBS programs in the Newborn Screening Technical assistance and Evaluation Program data repository. Data reported encompasses NBS state profile data (follow-up, disorder testing and the reporting of processes and methodologies for screening), quality indicator data (timeliness of CAH NBS) and confirmed cases. This comprehensive landscape analysis compares the CAH NBS systems across the US. This is vital in ultimately ensuring that newborns with CAH at risk of salt crisis receive appropriate intervention in a timely manner.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030063

Abstract:
In Australia, all newborns born in New South Wales (NSW) and the Australia Capital Territory (ACT) have been offered screening for rare congenital conditions through the NSW Newborn Screening Programme since 1964. Following the development of the Australian Newborn Bloodspot Screening National Policy Framework, screening for congenital adrenal hyperplasia (CAH) was included in May 2018. As part of the assessment for addition of CAH, the national working group recommended a two-tier screening protocol determining 17α-hydroxyprogesterone (17OHP) concentration by immunoassay followed by steroid profile. A total of 202,960 newborns were screened from the 1 May 2018 to the 30 April 2020. A threshold level of 17OHP from first tier immunoassay over 22 nmol/L and/or top 2% of the daily assay was further tested using liquid chromatography tandem mass spectrometry (LC-MS/MS) steroid profiling for 17OHP (MS17OHP), androstenedione (A4) and cortisol. Samples with a ratio of (MS17OHP + A4)/cortisol > 2 and MS17OHP > 200 nmol/L were considered as presumptive positive. These newborns were referred for clinical review with a request for diagnostic testing and a confirmatory repeat dried blood spot (DBS). There were 10 newborns diagnosed with CAH, (9 newborns with salt wasting CAH). So far, no known false negatives have been notified, and the protocol has a sensitivity of 100%, specificity of 99.9% and a positive predictive value of 71.4%. All confirmed cases commenced treatment by day 11, with none reported as having an adrenal crisis by the start of treatment.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030062

Abstract:
Since the start of X-linked adrenoleukodystrophy (ALD) newborn screening in California, more than half of the diagnosed cases were found to have an ATP binding cassette subfamily D member 1 (ABCD1) gene variant of uncertain significance (VUS). To determine retrospectively the likelihood that these were true positive cases, we used a web-based post-analytical tool in Collaborative Laboratory Integrated Reports (CLIR). Confirmatory plasma very long-chain fatty-acids (VLCFA) profiles for ALD screen positive infant boys were run through the CLIR ALD tool. We compared the distribution by ABCD1 variant classification (pathogenic, likely pathogenic, VUS, and no variant) with the CLIR tool score interpretation (non-informative, possibly ALD, likely ALD, and very likely ALD) and the current case diagnosis. The study showed that CLIR tool positive interpretations were consistent with 100% of the pathogenic and likely pathogenic variants on the ABCD1 gene if a more conservative guideline was used. The tool interpretations were also consistent with screened cases that were determined to not have disease (our no-disorder group). The CLIR tool identified 19 diagnosed ALD cases with VUS to be potential false positives, representing a 40% reduction among all diagnosed ALD cases with VUS. The reduction could be extended to 65% if a more aggressive threshold was used. Identifying such preventable false positives could alleviate the follow-up burden for patients, their families, and California Special Care Centers.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030061

Abstract:
In mid 2019, the author reminded the (International Society for Neonatal Screening) ISNS of the happy occasion of the 100th birthday of one of the living pioneers of neonatal screening, Professor Louis Isaac Woolf
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030060

Abstract:
Background: Homocystinuria (HCU) is a rare inherited metabolic disease. In Japan, newborn screening (NBS) for HCU (cystathionine β-synthase deficiency) was initiated in 1977. We compared the outcomes between patients detected by NBS (NBS group) and clinically detected patients (non-NBS group). Methods: We administered questionnaires about clinical symptoms and social conditions to 16 attending physicians of 19 adult HCU patients treated with methionine-free formula. Results: Eighteen patients (nine patients each in the NBS and non-NBS groups) participated. The frequency of patients with ocular, vascular, central nervous system, and skeletal symptoms in the NBS group was lower than that in the non-NBS group. Intellectual disability was observed in one and eight patients in the NBS and non-NBS groups, respectively. Concerning their social conditions, all patients in the NBS group were employed or still attending school, while only two patients in the non-NBS group were employed. Three of the four patients who discontinued treatment presented some symptoms, even in the NBS group. Conclusion: The social and intellectual outcomes of adult Japanese patients with HCU detected by NBS were favorable. However, even in the patients in the NBS group, some symptoms might not be preventable without continuous treatment.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030059

Abstract:
The story of phenylketonuria (PKU) started in 1934 with Asbjørn Følling’s examination of two mentally retarded siblings from a Norwegian family. However, if their mother had not been so persistent in her search for somebody who could give her a reason why both her children were retarded, Asbjørn Følling’s name might never have been associated with PKU and surely the history of PKU would have started differently. In the short review below, the authors give a partly personal and therefore rare account of the early history of PKU, its treatment and the start of neonatal screening. Prof. Woolf is a pioneer of both the dietary treatment of PKU and neonatal screening; Mr. Adams is a long-time advocate for PKU patient interests.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030058

Abstract:
Early detection of disabling diseases, prior to clinical manifestations, is the primary goal of newborn screening (NS). Indeed, the required number of core and secondary conditions selected for screening panels is increasing in many countries. Furthermore, newborn screening can lead to diagnosis of maternal diseases such as vitamin B12 deficiency or 3-MethylcrotonylCoA-carboxylase deficiency (3MCC). NS became mandatory in Sicily in December 2017. Here we report NS data collected between December 2017 and April 2020. Our results show that tandem mass spectrometry is a powerful tool for discovery of underestimated disease in newborns and their family members. Our panel included short chain acyl-CoA dehydrogenase deficiency (SCADD). Here, we report that results of our investigation led to reassessment of SCADD prevalence in our population. The infant and adult patients diagnosed in our study had previously not shown overt symptoms.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030057

Abstract:
Today, newborn screening (NBS) is considered an essential component in the standards of care for cystic fibrosis (CF)
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030056

Abstract:
The introduction and widespread implementation of newborn bloodspot screening (NBS) for cystic fibrosis (CF) has offered earlier diagnosis and better outcomes for children with CF in many countries of the world
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030055

Abstract:
When clinical trials for enzyme replacement therapy for Pompe disease commenced, a need for newborn screening (NBS) for Pompe disease was recognized. Two methods for NBS for Pompe disease by measuring acid α-glucosidase in dried blood spots on filter paper were developed in an international collaborative research effort led by Genzyme. Both methods were used successfully in NBS pilot programs to demonstrate the feasibility of NBS for Pompe disease. Since 2009, all babies born in Taiwan have been screened for Pompe disease. Pompe disease was added to the Recommended Uniform (Newborn) Screening Panel in the United States in 2015. NBS for Pompe disease is possible because of the unprecedented and selfless collaborations of countless international experts who shared their thoughts and data freely with the common goal of establishing NBS for Pompe disease expeditiously.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030054

Abstract:
Early diagnosis, multidisciplinary care, and optimized and preventive treatments have changed the face of cystic fibrosis. Life expectancy has been expanded in the last decades. Formerly a pediatric disease, cystic fibrosis has reached adulthood. Mutation-specific treatments will expand treatment options and give hope for further improvement of quality of life and life expectancy. Newborn screening for CF fits perfectly into these care structures and offers the possibility of preventive treatment even before symptoms occur. Especially in countries without screening, newborn screening will fulfill that promise only with increased awareness and new care structures.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030052

Abstract:
Severe combined immunodeficiency (SCID) includes a group of monogenic disorders presenting with severe T cell lymphopenia (TCL) and high mortality, if untreated. The newborn screen (NBS) for SCID, included in the recommended universal screening panel (RUSP), has been widely adopted across the US and in many other countries. However, there is a lack of consensus regarding follow-up testing to confirm an abnormal result. The Clinical Immunology Society (CIS) membership was surveyed for confirmatory testing practices for an abnormal NBS SCID result, which included consideration of gestational age and birth weight, as well as flow cytometry panels. Considerable variability was observed in follow-up practices for an abnormal NBS SCID with 49% confirming by flow cytometry, 39% repeating TREC analysis, and the remainder either taking prematurity into consideration for subsequent testing or proceeding directly to genetic analysis. More than 50% of respondents did not take prematurity into consideration when determining follow-up. Confirmation of abnormal NBS SCID in premature infants continues to be challenging and is handled variably across centers, with some choosing to repeat NBS SCID testing until normal or until the infant reaches an adjusted gestational age of 37 weeks. A substantial proportion of respondents included naïve and memory T cell analysis with T, B, and NK lymphocyte subset quantitation in the initial confirmatory panel. These results have the potential to influence the diagnosis and management of an infant with TCL as illustrated by the clinical cases presented herein. Our data indicate that there is clearly a strong need for harmonization of follow-up testing for an abnormal NBS SCID result.
Page of 5
Articles per Page
by
Show export options
  Select all
Back to Top Top