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Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is an X-linked condition caused by pathogenic variants in the iduronate-2-sulfatase gene. The resulting reduced activity of the enzyme iduronate-2-sulfatase leads to accumulation of glycosaminoglycans that can progressively affect multiple organ systems and impair neurologic development. In 2006, the US Food and Drug Administration approved idursulfase for intravenous enzyme replacement therapy for MPS II. After the data suggesting that early treatment is beneficial became available, 2 states, Illinois and Missouri, implemented MPS II newborn screening. Following a recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children in February 2022, in August 2022, the US Secretary of Health and Human Services added MPS II to the Recommended Uniform Screening Panel, a list of conditions recommended for newborn screening. MPS II was added to the Recommended Uniform Screening Panel after a systematic evidence review reported the accuracy of screening, the benefit of presymptomatic treatment compared with usual case detection, and the feasibility of implementing MPS II newborn screening. This manuscript summarizes the findings of the evidence review that informed the Advisory Committee's decision.
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Iduronato Sulfatase , Mucopolissacaridose II , Criança , Humanos , Recém-Nascido , Estados Unidos , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/genética , Triagem Neonatal , Ácido Idurônico , Iduronato Sulfatase/uso terapêutico , Glicosaminoglicanos , Terapia de Reposição de Enzimas/métodosRESUMO
Alpha-thalassemia comprises a group of inherited disorders in which alpha-hemoglobin chain production is reduced. Depending on the genotype, alpha-thalassemia results in moderate to profound anemia, hemolysis, growth delays, splenomegaly, and increased risk for thromboembolic events; certain patients might require chronic transfusions. Although alpha-thalassemia is not a core condition of the United States Recommended Uniform Screening Panel* for state newborn screening programs, methodologies used by some newborn screening programs to detect sickle cell disease, which is a core panel condition, also detect a quantitative marker of alpha-thalassemia, hemoglobin (Hb) Bart's, an abnormal type of hemoglobin. The percentage of Hb Bart's detected correlates with alpha-thalassemia severity. The Association of Public Health Laboratories' Hemoglobinopathy Workgroup conducted a survey of state newborn screening programs' alpha-thalassemia screening methodologies and reporting and follow-up practices. Survey findings indicated that 41 of 44 responding programs (93%) report some form of alpha-thalassemia results and 57% used a two-method screening protocol. However, the percentage of Hb Bart's used for thalassemia classification, the types of alpha-thalassemia reported, and the recipients of this information varied widely. These survey findings highlight the opportunity for newborn screening programs to revisit their policies as they reevaluate their practices in light of the recently released guideline from the Clinical and Laboratory Standards Institute (CLSI) on Newborn Screening for Hemoglobinopathies (1). Although deferring to local programs for policies, the report used a cutoff of 25% Hb Bart's in its decision tree, a value many programs do not use. Standardization of screening and reporting might lead to more timely diagnoses and health care services and improved outcomes for persons with a clinically significant alpha-thalassemia.
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Triagem Neonatal/métodos , Talassemia alfa/diagnóstico , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Recém-Nascido , Masculino , Estados Unidos/epidemiologia , Talassemia alfa/epidemiologiaRESUMO
Newborn screening (NBS) identifies infants at risk for congenital disorders for which early intervention has been shown to improve outcomes (1). State public health programs are encouraged to screen for disorders on the national Recommended Uniform Screening Panel (RUSP), which increased from 29 disorders in 2005 to 35 in 2018.* The RUSP includes hearing loss (HL) and critical congenital heart defects, which can be detected through point-of-care screening, and 33 disorders detected through laboratory screening of dried blood spot (DBS) specimens. Numbers of cases for 33 disorders on the RUSP (32 DBS disorders and HL) reported by 50 U.S. state programs were tabulated. The three subtypes of sickle cell disease (SCD) listed as separate disorders on the RUSP (S,S disease; S,beta-thalassemia; and S,C disease) were combined for the current analysis, and the frequencies of the resulting disorders were calculated relative to annual births. During 2015-2017, the overall prevalence was 34.0 per 10,000 live births. Applying that frequency to 3,791,712 live births in 2018, approximately 12,900 infants are expected to be identified each year with one of the disorders included in the study. The most prevalent disorder is HL (16.5 per 10,000), and the most prevalent DBS disorders are primary congenital hypothyroidism (CH) (6.0 per 10,000), SCD (4.9 per 10,000), and cystic fibrosis (CF) (1.8 per 10,000). Notable changes in prevalence for each of these disorders have occurred since the previous estimates based on 2006 births (2). The number of infants identified at a national level highlights the effect that NBS programs are having on infant health through early detection, intervention, and potential improved health, regardless of geographic, racial/ethnic, or socioeconomic differences.
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Anormalidades Congênitas/diagnóstico , Triagem Neonatal , Anormalidades Congênitas/epidemiologia , Humanos , Recém-Nascido , Prevalência , Estados Unidos/epidemiologiaRESUMO
The secretary of the US Department of Health and Human Services in February 2016 recommended that X-linked adrenoleukodystrophy (X-ALD) be added to the recommended uniform screening panel for state newborn screening programs. This decision was informed by data presented on the accuracy of screening from New York, the only state that currently offers X-ALD newborn screening, and published and unpublished data showing health benefits of earlier treatment (hematopoietic stem cell transplantation and adrenal hormone replacement therapy) for the childhood cerebral form of X-ALD. X-ALD newborn screening also identifies individuals with later-onset disease, but poor genotype-phenotype correlation makes predicting health outcomes difficult and might increase the risk of unnecessary treatment. Few data are available regarding the harms of screening and presymptomatic identification. Significant challenges exist for implementing comprehensive X-ALD newborn screening, including incorporation of the test, coordinating follow-up diagnostic and treatment care, and coordination of extended family testing after case identification.Genet Med 19 1, 121-126.
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Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP/genética , Adrenoleucodistrofia/genética , Triagem Neonatal , Adrenoleucodistrofia/diagnóstico , Adrenoleucodistrofia/patologia , Comitês Consultivos , Feminino , Humanos , Recém-Nascido , Masculino , Mutação , New York , Fenótipo , Estados Unidos , United States Dept. of Health and Human ServicesRESUMO
OBJECTIVE: To evaluate the expected cost-effectiveness and net benefit of the recent implementation of newborn screening (NBS) for severe combined immunodeficiency (SCID) in Washington State. STUDY DESIGN: We constructed a decision analysis model to estimate the costs and benefits of NBS in an annual birth cohort of 86â600 infants based on projections of avoided infant deaths. Point estimates and ranges for input variables, including the birth prevalence of SCID, proportion detected asymptomatically without screening through family history, screening test characteristics, survival rates, and costs of screening, diagnosis, and treatment were derived from published estimates, expert opinion, and the Washington NBS program. We estimated treatment costs stratified by age of identification and SCID type (with or without adenosine deaminase deficiency). Economic benefit was estimated using values of $4.2 and $9.0 million per death averted. We performed sensitivity analyses to evaluate the influence of key variables on the incremental cost-effectiveness ratio (ICER) of net direct cost per life-year saved. RESULTS: Our model predicts an additional 1.19 newborn infants with SCID detected preclinically through screening, in addition to those who would have been detected early through family history, and 0.40 deaths averted annually. Our base-case model suggests an ICER of $35â311 per life-year saved, and a benefit-cost ratio of either 5.31 or 2.71. Sensitivity analyses found ICER values <$100â000 and positive net benefit for plausible assumptions on all variables. CONCLUSIONS: Our model suggests that NBS for SCID in Washington is likely to be cost-effective and to show positive net economic benefit.
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Triagem Neonatal/economia , Imunodeficiência Combinada Severa/diagnóstico , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Humanos , Recém-Nascido , Modelos Teóricos , Sensibilidade e Especificidade , WashingtonRESUMO
BACKGROUND: The Department of Health and Human Services (HHS) Advisory Committee on Heritable Disorders in Newborns and Children ("Advisory Committee") makes recommendations to the HHS Secretary regarding addition of new conditions to the national Recommended Uniform Screening Panel for newborns. The Advisory Committee's decision-making process includes assessing the net benefit of screening for nominated conditions, informed by systematic evidence reviews generated by an independent Condition Review Workgroup. The evidence base regarding harms associated with screening for specific conditions is often more limited than that for benefits. PROCEDURES: The process for defining potential harms from newborn screening reviewed the frameworks from other public health evidence-based review processes, adapted to newborn screening by experts in systematic review, newborn screening programs and bioethics, with input from and approval by the Advisory Committee. MAIN FINDINGS: To support the Advisory Committee's review of nominated conditions, the Workgroup has developed a standardized approach to evaluation of harms and relevant gaps in the evidence. Types of harms include the physical burden to infants; psychosocial and logistic burdens to families from screening or diagnostic evaluation; increased risk of medical treatment for infants diagnosed earlier than children with clinical presentation; delayed diagnosis from false negative results; psychosocial harm from false positive results; uncertainty of clinical diagnosis, age of onset or clinical spectrum; and disparities in access to diagnosis or therapy. CONCLUSIONS: Estimating the numbers of children at risk, the magnitude, timing and likelihood of harms will be integrated into Workgroup reports to the Advisory Committee.
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Comitês Consultivos , Programas de Rastreamento , Triagem Neonatal/métodos , Avaliação de Programas e Projetos de Saúde , Tomada de Decisões , Medicina Baseada em Evidências , Feminino , Humanos , Lactente , Recém-Nascido , Programas Nacionais de SaúdeRESUMO
There is no clear consensus among state newborn screening programs on whether routine second screening of newborns identifies clinically relevant cases of congenital adrenal hyperplasia. This retrospective study evaluated laboratory practices, along with biochemical and medical characteristics of congenital adrenal hyperplasia (CAH) cases (1) detected on the first newborn screen in one-screen compared to two-screen states, and (2) detected on the first versus the second screen in the two-screen states, to determine the effectiveness of a second screen. A total of 374 confirmed cases of CAH from 2 one-screen states and 5 two-screen states were included in this study. Demographic data and diagnostic information on each reported case were collected and analyzed. Additionally, laboratory data, including screening methodologies and algorithms, were evaluated. The one-screen states reported 99 cases of CAH out of 1,740,586 (1 in 17,500) newborns screened: 88 (89%) identified on the first screen and 5 (5%) identified on the targeted second screen. The two-screen states reported 275 cases of CAH out of 2,629,627 (1 in 9500) newborns screened: 165 (60%) identified on the first screen and 99 (36%) identified on the second screen. Using a multivariate model, the only significant predictor of whether a case was identified on the first or the second screen in the two-screen states was the type of CAH. Compared with classical salt-wasting CAH, classical simple virilizing and non-classical CAH cases were less likely to be detected on the first versus the second screen. The routine second newborn screen is important for identifying children with CAH, particularly simple virilizing and non-classical forms, which might otherwise not be captured through a single screen.
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Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/epidemiologia , Triagem Neonatal/métodos , Algoritmos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Routine second screening of most newborns at 8-14 days of life for a panel of newborn conditions occurs in 12 U.S. states, while newborns in the other states typically undergo only a single routine newborn screen. The study objective was to evaluate screening consequences for primary congenital hypothyroidism (CH) in one- and two-screen states according to laboratory practices and medical or biochemical characteristics of screen-positive cases. Individual-level medical and biochemical data were retrospectively collected and analyzed for 2251 primary CH cases in one-screen (CA, WI) and two-screen (AL, DE, MD, OR, TX) states. Aggregate data were collected and analyzed for medical and biochemical characteristics of all screened newborns in the states. Among the states evaluated in this study, the detection rate of primary CH was higher in the one-screen states. In the two-screen states, 11.5% of cases were detected on the second screen. In multivariate analyses, only race/ethnicity was a significant predictor of cases identified on the first versus second screen, which likely reflects a physiologic difference in primary CH presentation. Newborn screening programs must heed the potential for newborns with CH not being detected by a single screen, particularly newborns of certain races/ethnicities. If the two-screen states converted to a single screen using their current algorithms, newborns currently identified on the routine second screen would presumably not be detected, resulting in probable delayed diagnosis and treatment. However, based on the one-screen state experiences, with appropriate modifications in screening method and algorithm, the two-screen states might convert to single screen operation for CH without loss in performance.
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Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/epidemiologia , Triagem Neonatal/métodos , Algoritmos , Hipotireoidismo Congênito/etnologia , Humanos , Recém-Nascido , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
PURPOSE: The US Secretary of Health and Human Services provides guidance to state newborn screening programs about which conditions should be included in screening (i.e., the "Recommended Uniform Screening Panel"). This guidance is informed by evidence-based recommendations from the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children. This report describes the Advisory Committee's revised decision-making process for considering conditions nominated to the panel. METHODS: An expert panel meeting was held in April 2012 to revise the decision matrix, which helps to guide the recommendation process. In January 2013, the Advisory Committee voted to adopt the revised decision matrix. RESULTS: The revised decision matrix clarifies the approach to rating magnitude and certainty of the net benefit of screening to the population of screened newborns for nominated conditions, and now includes the consideration of the capability of state newborn screening programs for population-wide implementation by evaluating the feasibility and readiness of states to adopt screening for nominated conditions. CONCLUSION: The revised decision matrix will bring increased quality, transparency, and consistency to the process of modifying the recommended uniform screening panel and will now allow formal evaluation of the challenges that state newborn screening programs face in adopting screening for new conditions.
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Comitês Consultivos , Tomada de Decisões , Medicina Baseada em Evidências , Triagem Neonatal/normas , United States Dept. of Health and Human Services , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Estados UnidosRESUMO
Persons with sickle cell trait (SCT) are heterozygous carriers of an abnormal ß-globin gene that results in the production of an abnormal hemoglobin, Hb S, which can distort red blood cells (http://www.cdc.gov/ncbddd/sicklecell/facts.html). All state newborn screening (NBS) programs have provided universal sickle cell disease (SCD) screening for newborns since 2006. Screening for SCD detects both SCD and SCT. To obtain up-to-date measures of the occurrence of SCT among newborns by race/ethnicity and state of birth, data collected by state NBS programs in 2010 were examined. In 2010, the incidence of SCT in participating states was 15.5 per 1,000 newborns overall; 73.1 among black newborns and 6.9 among Hispanic newborns. Incidence by state ranged from 0.8 per 1,000 screened newborns in Montana to 34.1 per 1,000 in Mississippi. Although the occurrence of SCT varies greatly from state-to-state and among different races and ethnicities, every state and racial/ethnic population includes persons living with the condition. The period immediately following NBS is ideal for primary care providers and genetic counselors to begin educating the families of identified persons with SCT about potential health complications and reproductive considerations.
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Traço Falciforme/epidemiologia , Hispânico ou Latino/estatística & dados numéricos , Humanos , Incidência , Recém-Nascido , Triagem Neonatal , Grupos Raciais/estatística & dados numéricos , Traço Falciforme/etnologia , Estados Unidos/epidemiologiaRESUMO
Newborn screening (NBS) is a state or territory-based public health system that screens newborns for congenital diseases that typically do not present with clinical symptoms at birth but can cause significant mortality and morbidity if not detected or treated quickly. NBS continues to be one of the most successful public health interventions in the US, providing early detection and intervention to all infants. The increase in overall birth prevalence of core Recommended Uniform Screening Panel (RUSP) diseases detected via dried blood spot (DBS) specimens from 2015-2017 (17.50-18.31 per 10,000) to 2018-2020 (20.07 per 10,000), as reported into the APHL NewSTEPs database, affirms the importance and impact of NBS programs. This report presents aggregate numbers and birth prevalence of diseases detected by DBS on the RUSP from 2018-2020, including data from fifty US states and two territories.
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The Recommended Uniform Screening Panel (RUSP) is the list of conditions recommended by the US Secretary of Health and Human Services for inclusion in state newborn screening (NBS). During 2010-2022, seven conditions were added to the RUSP: severe combined immunodeficiency (SCID) (2010), critical congenital heart disease (CCHD) (2011), glycogen storage disease, type II (Pompe) (2015), mucopolysaccharidosis, type I (MPS I) (2016), X-linked adrenoleukodystrophy (X-ALD) (2016), spinal muscular atrophy (SMA) (2018), and mucopolysaccharidosis, type II (MPS II) (2022). The adoption of SCID and CCHD newborn screening by programs in all 50 states and three territories (Washington, D.C.; Guam; and Puerto Rico) took 8.6 and 6.8 years, respectively. As of December 2022, 37 programs screen for Pompe, 34 for MPS I, 32 for X-ALD, and 48 for SMA. The pace of implementation based on the average additional number of NBS programs per year was most rapid for SMA (11.3), followed by CCHD (7.8), SCID (6.2), MPS I (5.4), Pompe (4.9), and X-ALD (4.7).
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Introduction and Abstracts of the 2023 APHL/ISNS Newborn Screening Symposium in Sacramento, CA, USA from 15-19 October 2023.
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Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine biosynthesis due to pathogenic variants in the GAMT gene that lead to cerebral creatine deficiency and neurotoxic levels of guanidinoacetate. Untreated, GAMT deficiency is associated with hypotonia, significant intellectual disability, limited speech development, recurrent seizures, behavior problems, and involuntary movements. The birth prevalence of GAMT deficiency is likely between 0.5 and 2 per million live births. On the basis of small case series and sibling data, presymptomatic treatment with oral supplements of creatine, ornithine, and sodium benzoate, and a protein-restricted diet to reduce arginine intake, appear to substantially improve health and developmental outcomes. Without newborn screening, diagnosis typically happens after the development of significant impairment, when treatment has limited utility. GAMT deficiency newborn screening can be incorporated into the tandem-mass spectrometry screening that is already routinely used for newborn screening, with about 1 per 100 000 newborns screening positive. After a positive screen, diagnosis is established by finding an elevated guanidinoacetate concentration and low creatine concentration in the blood. Although GAMT deficiency is significantly more rare than other conditions included in newborn screening, the feasibility of screening, the low number of positive results, the relative ease of diagnosis, and the expected benefit of presymptomatic dietary therapy led to a recommendation from the Advisory Committee on Heritable Disorders in Newborns and Children to the Secretary of Health and Human Services that GAMT deficiency be added to the Recommended Uniform Screening Panel. This recommendation was accepted in January 2023.
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Transtornos do Desenvolvimento da Linguagem , Transtornos dos Movimentos , Criança , Humanos , Recém-Nascido , Guanidinoacetato N-Metiltransferase/genética , Creatina , Triagem Neonatal/métodos , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/genética , Transtornos dos Movimentos/terapiaRESUMO
On May 23-24, 2011, a workshop entitled "Immunoreactive Trypsinogen (IRT) as a Biomarker for Cystic Fibrosis: Technical Issues and Challenges" was held in Annapolis, Maryland. The two-day workshop was co-hosted by the National Newborn Screening and Genetics Resource Center, Austin, Texas, and the Association of Public Health Laboratories, Silver Spring, Maryland, in collaboration with the Health Resources and Services Administration and the Centers for Disease Control and Prevention. Participants included nearly 40 representatives from U.S. state public health and commercial laboratories performing newborn dried blood spot screening tests for cystic fibrosis (CF), the federal government, academic research institutions, and commercial vendors of products used in newborn screening. Representatives from selected European CF newborn screening programs were also present. The workshop focused on identifying key IRT testing issues and mechanisms for achieving their resolution and laboratory harmonization in order to reduce, or eliminate completely, the late identified CF cases following a negative newborn screen. Informative findings are reported, their impacts on improving IRT screening are described, and their implications are discussed.
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Fibrose Cística/diagnóstico , Teste em Amostras de Sangue Seco/métodos , Tripsinogênio/imunologia , Biomarcadores , Testes Genéticos , Humanos , Tripsinogênio/sangue , Tripsinogênio/genéticaRESUMO
Judith "Judi" Tuerck, RN, MS, one of the true pioneers in the development of newborn screening (NBS), passed away on Saturday, 18 June 2022 (Figure 1) [...].
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Newborn screening (NBS) is an essential public health service that performs screening to identify those newborns at increased risk for a panel of disorders, most of which are genetic. The goal of screening is to link those newborns at the highest risk to timely intervention and potentially life-saving treatment. The global COVID-19 pandemic led to disruptions within the United States public health system, revealing implications for the continuity of newborn screening laboratories and follow-up operations. The impacts of COVID-19 across different states at various time points meant that NBS programs impacted by the pandemic later could benefit from the immediate experiences of the earlier impacted programs. This article will review the collection, analysis, and dissemination of information during the COVID-19 pandemic facilitated by a national, centralized technical assistance and resource center for NBS programs.
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Newborn screening (NBS) programs identify newborns at increased risk for genetic disorders, linking these newborns to timely intervention and potentially life-saving treatment. In the United States, the Health and Human Services (HHS) Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) recommends the disorders for state NBS programs to screen. ACHDNC updated the Recommended Uniform Screening Panel to include Spinal Muscular Atrophy (SMA) in July 2018. As of June 2021, 34 state NBS programs had fully implemented SMA newborn screening, and at least 8 programs were pursuing implementation. This article will review current SMA screening processes, considerations, challenges, and status.
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Newborn screening (NBS) follow-up programs in the United States are managed at the state level, leaving limited opportunities for collaboration across programs and coordinated resource sharing. The Newborn Screening Technical assistance and Evaluation Program (NewSTEPs), a program of the Association of Public Health Laboratories (APHL), has established a national community of practice for NBS follow-up by creating a network of follow-up staff and stakeholders through education and engagement opportunities. The activities of NewSTEPs in support of NBS follow-up have strengthened information dissemination, collaboration, data collection and technical assistance-driven mentorship across the national system.