Expansion Of Newborn Screening Programs Research Articles

Expansion of Newborn Screening Programs: Implications and Strategies for Implementation

Expansion of Newborn Screening Programs: Implications and Strategies for Implementation

Exome/Genome-Wide Testing in Newborn Screening: A Proportionate Path Forward.

Population-based newborn screening (NBS) is among the most effective public health programs ever launched, improving health outcomes for newborns who screen positive worldwide through early detection and clinical intervention for genetic disorders discovered in the earliest hours of life. Key to the success of newborn screening programs has been near universal accessibility and participation. Interest has been building to expand newborn screening programs to also include many rare genetic diseases that can now be identified by exome or genome sequencing (ES/GS). Significant declines in sequencing costs as well as improvements to sequencing technologies have enabled researchers to elucidate novel gene-disease associations that motivate possible expansion of newborn screening programs. In this paper we consider recommendations from professional genetic societies in Europe and North America in light of scientific advances in ES/GS and our current understanding of the limitations of ES/GS approaches in the NBS context. We invoke the principle of proportionality—that benefits clearly outweigh associated risks—and the human right to benefit from science to argue that rigorous evidence is still needed for ES/GS that demonstrates clinical utility, accurate genomic variant interpretation, cost effectiveness and universal accessibility of testing and necessary follow-up care and treatment. Confirmatory or second-tier testing using ES/GS may be appropriate as an adjunct to conventional newborn screening in some circumstances. Such cases could serve as important testbeds from which to gather data on relevant programmatic barriers and facilitators to wider ES/GS implementation.

Comparison of Untargeted Metabolomic Profiling vs Traditional Metabolic Screening to Identify Inborn Errors of Metabolism

Recent advances in newborn screening (NBS) have improved the diagnosis of inborn errors of metabolism (IEMs); however, many potentially treatable IEMs are not included on NBS panels, nor are they covered in standard, first-line biochemical testing. To examine the utility of untargeted metabolomics as a primary screening tool for IEMs by comparing the diagnostic rate of clinical metabolomics with the recommended traditional metabolic screening approach. This cross-sectional study compares data from 4464 clinical samples received from 1483 unrelated families referred for trio testing of plasma amino acids, plasma acylcarnitine profiling, and urine organic acids (June 2014 to October 2018) and 2000 consecutive plasma samples from 1807 unrelated families (July 2014 to February 2019) received for clinical metabolomic screening at a College of American Pathologists and Clinical Laboratory Improvement Amendments-certified biochemical genetics laboratory. Data analysis was performed from September 2019 to August 2020. Metabolic and molecular tests performed at a genetic testing reference laboratory in the US and available clinical information for each patient were assessed to determine diagnostic rate. The diagnostic rate of traditional metabolic screening compared with clinical metabolomic profiling was assessed in the context of expanded NBS. Of 1483 cases screened by the traditional approach, 912 patients (61.5%) were male and 1465 (98.8%) were pediatric (mean [SD] age, 4.1 [6.0] years; range, 0-65 years). A total of 19 families were identified with IEMs, resulting in a 1.3% diagnostic rate. A total of 14 IEMs were detected, including 3 conditions not included in the Recommended Uniform Screening Panel for NBS. Of the 1807 unrelated families undergoing plasma metabolomic profiling, 1059 patients (58.6%) were male, and 1665 (92.1%) were pediatric (mean [SD] age, 8.1 [10.4] years; range, 0-80 years). Screening identified 128 unique cases with IEMs, giving an overall diagnostic rate of 7.1%. In total, 70 different metabolic conditions were identified, including 49 conditions not presently included on the Recommended Uniform Screening Panel for NBS. These findings suggest that untargeted metabolomics provided a 6-fold higher diagnostic yield compared with the conventional screening approach and identified a broader spectrum of IEMs. Notably, with the expansion of NBS programs, traditional metabolic testing approaches identify few disorders beyond those covered on the NBS. These data support the capability of clinical untargeted metabolomics in screening for IEMs and suggest that broader screening approaches should be considered in the initial evaluation for metabolic disorders.

Next-generation sequencing of newborn screening genes: the accuracy of short-read mapping

Newborn screening programs are an integral part of public health systems aiming to save lives and improve the quality of life for infants with treatable disorders. Technological advancements have driven the expansion of newborn screening programs in the last two decades and the development of fast, accurate next-generation sequencing technology has opened the door to a range of possibilities in the field. However, technological challenges with short-read next-generation sequencing technologies remain significant in highly homologous genomic regions such as pseudogenes or paralogous genes and need to be considered when implemented in screening programs. Here, we simulate 50 genomes from populations around the world to test the extent to which high homology regions affect short-read mapping of genes related to newborn screening disorders and the impact of differential read lengths and ethnic backgrounds. We examine a 158 gene screening panel directly relevant to newborn screening and identify gene regions where read mapping is affected by homologous genomic regions at different read lengths. We also determine that the patient’s ethnic background does not have a widespread impact on mapping accuracy or coverage. Additionally, we identify newborn screening genes where alternative forms of sequencing or variant calling pipelines should be considered and demonstrate that alterations to standard variant calling can retrieve some formerly uncalled variants.

Mandatory newborn screening in the United States: History, current status, and existential challenges.

Beginning in the 1960s, mandatory newborn screening (NBS) of essentially all infants has been a major public health success story. NBS is not just a blood test, rather, it is a complex, integrated system that begins with timely testing, scrupulous follow up of patients, tracking of outcomes, quality improvement of all aspects of the process, and education of providers, staff, and parents. In the past, expansion of NBS programs has been driven by new testing technology, but now is increasingly driven by the development of novel therapeutics and political advocacy. Each state determines how the NBS system will be structured in that state, but there is increasing oversight and support for harmonization at a federal level. Several recent initiatives, together with the increased number of conditions screened and the concomitant increase in burdensome false-positive tests, are creating new scrutiny of NBS systems, and potentially pose an existential risk to the public acceptance of mandatory NBS. The history, current state and challenges for NBS are explored in this issue, with some suggestions as to how to address them.

Expanded Newborn Screening: Challenges to NICU Nurses.

Newborn screening programs provide testing for all newborns born in this country for conditions that can potentially cause death or disability. Currently each state is responsible for its programs and the number of disorders screened varies from state to state. The current universal recommended metabolic screening panel may include 32 to 58 disorders. Expansion of the programs has impacted the role of nurses in the neonatal intensive care units (NICUs). Nurses are responsible for facilitating the screening process, educating the family, and assisting with follow-up. In addition, they are the first-line defense for emotional, spiritual, and social support. To review of the expansion of this program over time and discuss challenges the NICU nurse encounters. Research literatures along with the national recommendation by governmental and professional agencies were reviewed to obtain evidence on current practice recommendations. NICU nurses face several challenges with the expansion of newborn screening programs. This includes gaining knowledge to answer questions posed by empowered parents and educate them appropriately; ensuring quality of the process that minimizes errors and optimal communication; and, addressing ethical concerns about the storage and subsequent use of specimens. New and ongoing research can measure and ensure provision of quality services provided through the NICUs globally.

Facilitators and barriers to expansion of newborn screening programs in the 21st century

Abstract Background - Newborn screening programs have grown over the past 50 years to include screening for more than 40 metabolic and genetic disorders. Technology, or the ability to screen for disorders, is not the sole influence for expansion of screening. The lack of clarity in how facilitators and barriers impact newborn screening programs can affect the stakeholder’s perspective of public health department initiatives and future goals. Method - We developed a logic model in order to help stakeholders establish reasonable expectations, while being aware of the delays and unanticipated consequences which might occur when attempting to expand newborn screening programs. Results and Conclusions - Our logic model emphasizes that expansion of Newborn Screening relies on several interrelated factors that can be identified as Technical, Financial, Policy and Human Capital. Further delineating these factors into a series of checklists promises to be of value to decision-makers in state-operated newborn screening programs, given constrained resources and anticipated barriers.

In This Issue

see Developing a public health-tracking system for follow-up of newborn screening metabolic conditions: a four-state pilot project structure and initial findings The nationwide expansion of newborn screening programs provides an opportunity to better understand how early identification affects health outcomes of children. But lack of standardized data collection and of collaborative long-term follow-up has hindered efforts to determine whether children diagnosed with metabolic disorders receive appropriate health-care services. To address this issue, the US Centers for Disease Control and Prevention funded a three-year pilot project to expand and enhance public health data-collection programs in four states: California, Iowa, New York, and Utah. The authors report that the project not only improved state-level data but also, importantly, provided pooled data that sped the process of acquiring sufficient information to better understand how these rare disorders affect health outcomes. A total of 261 infants diagnosed with 1 of 19 metabolic disorders were followed through age 3. The research revealed that 88% received care at a metabolic clinic at least once in their first year of life. Those figures fell slightly to 77% in their second year and 74% in their third year. In the first year of follow-up, almost all the children (94%) saw a metabolic geneticist at least once; most (78%) also saw a metabolic dietitian, and half received services from a genetic counselor. The authors argue that continuing to track the long-term outcome of children diagnosed with metabolic disorders through newborn screening is necessary to maintain quality of care, identify areas for improvement, and observe the epidemiology of disorders recently added to the screening panel. —Karyn Hede, News Editor see Impact of prenatal technologies on the sex ratio in India: an overview and Prenatal technologies and the sex ratio Noninvasive prenatal testing undoubtedly serves a vital role in early detection of genetic defects, but the authors of a review and an accompanying commentary in this issue bring critical focus to the technology’s darker uses. Widespread use of prenatal diagnostic technologies to discover a fetus’ sex early in pregnancy has led to highly skewed female-to-male ratios in China and (the focus of the review) in India. The review’s authors draw troubling correlations between low female birth rates in several Indian provinces and higher levels of violence against women. They point out that, despite Indians’ ingrained cultural preference for a boy, the problem had previously been contained. Recently, however, it has resurfaced owing to the availability of increasingly common and inexpensive methods for prenatal sex selection as well as financially burdensome demands for brides’ dowries. The ability to identify a male fetus via noninvasive prenatal testing, available since the mid-2000s, is further encouraging prenatal sex determination, the authors state. They report that India’s current female/male sex ratio of 0.914 among children under 6 is historically low and that in some areas, it is well below 0.9. In his related commentary, Peter Benn, Director of Diagnostic Human Genetics Laboratories at the University of Connecticut Health Center, argues that clinical geneticists must confront these difficult moral quandaries: “The example of prenatal gender identification illustrates that even the most basic genetic information can fundamentally affect societies in worrisome ways.” He notes that the recent public outcry about gruesome crimes against women in India could be used to put pressure on authorities to enforce laws banning prenatal sex selection. —Karyn Hede, News Editor

Newborn Screening Policy and Practice Issues for Nurses

Advanced biomedical and genetic technologies are transforming newborn screening (NBS) programs. Nurses who work with families across perinatal care settings require knowledge of the policies that guide NBS practices and the controversies posed by the rapid application of genetic research to NBS. We provide an overview of NBS, outline challenges generated by expansion of NBS programs, and discuss implications for the nurses, nurse practitioners, and midwives in clinical practice, education, and research.

Implications of Newborn Screening for Nurses

Newborn screening has dramatically decreased the morbidity and mortality associated with a wide range of heritable conditions. Continuing advances in screening technology and improvements in the effectiveness of treatment are driving the rapid expansion of newborn screening programs. In this article, we review issues in newborn screening care and opportunities for nurses and nursing faculty to provide education and conduct research to improve the impact of newborn screening. This article provides (a) an overview of current newborn screening activities, including how conditions are added to newborn screening panels and how implementation occurs at state and national levels; (b) a description of current controversies and ethical considerations; (c) a description of the roles of nurses in the newborn screening process; (d) suggestions for nursing education and research; and (e) a summary of expected future developments in newborn screening, including genome sequencing. Nurses are uniquely well suited to address the educational needs and future research in newborn screening because of the role that nurses play in the provision of direct clinical care and in population-based healthcare delivery. Newborn screening is a public health approach to the identification of rare but treatable conditions in early infancy. In the United States, as in other industrialized countries, newborn screening is rapidly expanding. Nurses, nurse educators, and nurse researchers are positioned to contribute to the field of newborn screening by assuring programs are implemented safely and effectively, by facilitating education of the nursing work force, and by developing and contributing to research programs in newborn screening.

Rapid and Effective Screening for Lysosomal Storage Disease: How Close Are We?

The introduction of tandem mass spectrometry (MS/MS)1 into newborn screening programs during the past 15 years has been revolutionary, and it has resulted in a marked expansion of the number of detectable metabolic disorders, from a handful to more than 30(1). The majority of these are defects of amino acid and fatty acid transport and catabolism, and most are responsive to treatment. The success of this development has prompted much interest in further expansion of newborn screening programs, particularly for lysosomal storage disorders (LSDs) that cause significant morbidity and mortality. Until recently, these disorders received low priority(2) because of the lack of effective treatment and practicable screening methodologies. Enzyme replacement and bone marrow transplant therapies have become available for several LSDs, however, and other therapies are under development(3), giving new hope for affected individuals. Furthermore, the development of viable screening methods based on measurements of lysosomal enzyme activities in dried blood spots (DBS) has paved the way for newborn screening for these disorders(4). Enzyme activities of LSDs in DBS have been measured successfully both spectrofluorometrically, using substrates that release the fluorophore 4-methylumbelliferone(5)(6), and by tandem mass spectrometry, using substrates that are, for some of these assays, more closely related to or homologous with the natural enzyme precursors(7). The MS/MS method has the advantage that it can detect multiple enzyme products simultaneously because each product has a different m/z . In this issue of Clinical Chemistry , 2 papers(8)(9) address developments with MS/MS-based enzyme assays that bring the newborn screening option for LSDs a step closer to reality. Zhang et al.(8) describe substantial methodological improvements to the MS/MS-based method developed by Li et al.(7) for multiplex assays of up to 5 lysosomal enzyme activities. This assay …

Rapid 2nd-Tier Test for Measurement of 3-OH-Propionic and Methylmalonic Acids on Dried Blood Spots: Reducing the False-Positive Rate for Propionylcarnitine during Expanded Newborn Screening by Liquid Chromatography–Tandem Mass Spectrometry

The expansion of newborn screening programs has increased the number of newborns diagnosed with inborn errors of metabolism in the presymptomatic phase, but it has also increased the number of costly, stress-producing false-positive results. Because propionylcarnitine (C3) is one of the analytes most frequently responsible for false-positive results, we aimed to develop a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to identify free methylmalonic (MMA) and 3-OH propionic (3OH-PA) acids in blood spots. We studied newborn screening spots from 250 healthy controls; 124 from infants with abnormal C3, of whom only 5 (4%) were truly affected; 124 from infants with altered isolated methylmalonylcarnitine; and 4 from clinically diagnosed patients. Whole blood was eluted from a 3.2-mm dried blood spot by a CH(3)CN/H(2)O 7:3 and 5 mL/L formic. This extract was injected into a LC-MS/MS equipped with pneumatically assisted electrospray without derivatization. Total analysis time was 5 min per sample. The assays were linear up to 3300 nmol/L for both metabolites. Intra- and interassay imprecision data were 3.6%-8% and 3.1%-6%, respectively, for MMA and 5.2%-20% and 3.6%-17% for 3OH-PA. Limit of detection and limit of quantitation were 1.95 and 4.2 micromol/L, respectively, for MMA and 8 and 10 micromol/L for 3OH-PA. The recoveries were 92.9%-106.1%. No deterioration was noted on the columns after 500 chromatographic runs. If the new method had been used as a 2nd-tier test for the 124 samples, only the 5 true positives would have been recalled for additional samples, and the positive predictive value would have been 100%. This method has the potential to markedly reduce false-positive results and the associated costs and anxiety. It may also be suitable for diagnosing and routinely monitoring blood spots for methylmalonic aciduria and propionic acidemia.

In vitro characterization and in vivo expression of human very-long chain acyl-CoA dehydrogenase

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a disorder of fatty acid beta-oxidation that can present at any age with cardiomyopathy, rhabdomyolysis, hepatic dysfunction, and/or nonketotic hypoglycemia. Through the expansion of newborn screening programs an increasing number of individuals with VLCAD deficiency are being identified prior to the onset of symptoms allowing early initiation of therapy. The development of a safe, durable, and effective VLCAD gene delivery system for use at the time of diagnosis could result in a significant improvement in the quality and duration of life for patients with VLCAD deficiency. To this end, we developed a construct containing the human VLCAD cDNA under the control of the strong CMV promoter (pCMV-hVLCAD). A novel rabbit polyclonal anti-VLCAD antibody was prepared using a 24 amino-acid peptide unique to the human VLCAD protein to study human VLCAD expression in immune competent mice. Antibody specificity was demonstrated in Western blots of human VLCAD deficient fibroblasts and in pCMV-hVLCAD transiently transfected VLCAD deficient fibroblasts. Transfected fibroblasts showed correction of the metabolic block as demonstrated by normalization of C14- and C16-acylcarnitine species in cell culture media and restoration of VLCAD activity in cells. Following tail vein injection of pCMV-hVLCAD into mice, we demonstrated expression of hVLCAD in liver. Altogether, these steps are important in the development of a durable gene therapy for VLCAD deficiency.

Making the case for objective performance metrics in newborn screening by tandem mass spectrometry

The expansion of newborn screening programs to include multiplex testing by tandem mass spectrometry requires understanding and close monitoring of performance metrics. This is not done consistently because of lack of defined targets, and interlaboratory comparison is almost nonexistent. Between July 2004 and April 2006 (N=176,185 cases), the overall performance metrics of the Minnesota program, limited to MS/MS testing, were as follows: detection rate 1:1,816, positive predictive value 37% (54% in 2006 till date), and false positive rate 0.09%. The repeat rate and the proportion of cases with abnormal findings actually been reported are new metrics proposed here as an objective mean to express the overall noise in a program, where noise is defined as the total number of abnormal results obtained using a given set of cut-off values. On the basis of our experience, we propose the following targets as evidence of adequate analytical and postanalytical performance: detection rate 1:3,000 or higher, positive predictive value>20%, and false positive rate<0.3%.

Metabolic basis of pediatric heart disease

We review cardiomyopathies and their classification due to inborn errors of metabolism. An overview of their clinical presentations, diagnosis, treatment, and long-term outcome is provided. Due to the expansion of newborn screening programs and the widespread availability of genetic testing, many patients are now diagnosed earlier in life allowing for timely initiation of symptomatic or even curative treatment and providing opportunities for long-term survival. Hence, it is important that clinicians are familiar with the evaluation, diagnostic approach, and management of these hitherto often lethal pediatric cases. In addition, clinicians need a basic understanding of genetic concepts to provide for appropriate first tier counseling of patients and their families.

Newborn screening: An overview with an update on recent advances

Since its inception in the 1960s, newborn screening has provided valuable services with regard to detecting infants afflicted with inherited and sporadic chronic disorders and providing prompt medical intervention to prevent serious short- and long-term consequences. Technologic advances have enabled screening programs to greatly expand the number of disorders that can be detected. However, we are currently in a transitional period in which only a minority of states offer expanded screening. The challenge will be to expand newborn screening for those disorders in which presymptomatic detection and intervention improve outcome. The ability to adapt DNA mutation methods to the screening specimen is likely to result in expanded screening possibilities in the future as the knowledge gained by our understanding of genetic diseases increases. Uniformity of screening protocols from state to state is needed to ensure that all newborns with inherited disorders benefit from early detection. Expansion of newborn screening programs and resources to include patient education and tracking of long-term outcomes is also highly desirable.

Expanded Newborn Screening in Bavaria: Tracking to Achieve Requested Repeat Testing

Objectives. Expansion of newborn screening programs may increase the risk of missing cases through procedural failures. A coordinated process quality assurance procedure to track recalls was, therefore, introduced in parallel to expansion (including MS-MS and 17α-OHP) in Bavaria.Methods. Using comprehensive computerized registration and automated monitoring a state-funded center coordinated all individual measures to achieve complete testing of all repeat requests—case-specific contacts to physicians, midwives, and parents. Mailing and phoning from the center were supplemented by local public health activities including home visits if needed.Results. Among 243,422 children tested in 1999 and 2000 overall recall was 3.62% (8,809 children): 0.30% (726) were due to sample inadequacy, 1.35% (3,282) to early sampling (<48 h), and 1.97% (4,801) to abnormal results. Of all recalls, 80.9% were received following the initial request, 1,679 (19.1%) required special efforts. Of these, 873 were achieved following a single and 601 following repeated central activities, and 102 were achieved following local support. Sixty-three cases of parental refusal and 47 untraceable children remained. Altogether, 98.8% recalls were achieved, corresponding to 99.96% of all tested children for which definite screening results could be obtained.Conclusions. Expansion of newborn screening programs does not necessarily mean unsolvable problems in tracking of recalls if adequate logistics is established in parallel.

Newborn Screening by Tandem Mass Spectrometry

After completing this article, readers should be able to: 1. List examples of disorders for which tandem mass spectrometry (MS/MS) can screen. 2. Delineate potential difficulties with MS/MS newborn screening. Tandem mass spectrometry (MS/MS) technology has shown tremendous promise in newborn screening pilot programs worldwide with its capacity to measure numerous metabolites from a dried blood spot virtually simultaneously with an extremely rapid throughput per sample (approximately 2 min). The expansion of newborn screening programs by inclusion of an additional 15 to 30 metabolic disorders has the potential to decrease significantly the morbidity and mortality associated with inborn errors of metabolism and could offer the clinician critical diagnostic information when caring for an acutely ill neonate. Newborn screening for metabolic disorders began in 1962 in the United States, with the introduction of the Guthrie bacterial inhibition assay for phenylketonuria (PKU) in a Massachusetts voluntary program. Child health advocates, including the National Association for Retarded Citizens and the March of Dimes Birth Defects Foundation, developed model legislation and lobbied for passage of newborn screening laws at the state level. As a result of these efforts, newborn screening for PKU was legally mandated in most states in the early 1960s. The success of newborn screening for PKU led to development of tests for other conditions, including metabolic disorders (eg, galactosemia, maple syrup urine disease [MSUD], homocystinuria, and biotinidase deficiency), endocrinopathies (eg, congenital hypothyroidism and congenital adrenal hyperplasia), hemoglobinopathies (eg, sickle cell disease and thalassemias), and cystic fibrosis. Different states screen for a variable number of these disorders, with most screening for three to six conditions (Figure⇓ ). Such differences reflect state political and economic environments, technologic capabilities of public health departments, regional ethnic composition, and community expectations. All states screen for PKU and congenital hypothyroidism, and 48 states screen for galactosemia. Other inborn …

Preface

Each year the 4 million infants born in the United States are screened shortly after birth to detect a variety of congenital conditions. These public health screening programs have become models for population-based screening. Newborn screening programs in this country began with the work of Dr Robert Guthrie in the 1960s with the development of a screening test for phenylketonuria (PKU). Today, all states screen for a wide range of conditions. However, the array of screening tests performed by each state varies and changes periodically. The variability reflects differences in community values, in state political and economic environments, and in technical capabilities.The Health Resources and Services Administration's (HRSA) Maternal and Child Health programs have supported the development of these programs from their inception. HRSA funded the early work of Dr Guthrie to develop the screening test for PKU, sponsored cost-effectiveness studies for the PKU screening test, and facilitated the expansion of newborn screening programs to include screening tests for sickle cell anemia. In recognition of this historical involvement with state newborn screening programs, HRSA requested the American Academy of Pediatrics (AAP) to convene The Task Force on Newborn Screening. Genuine concern for the health of infants and children demands a periodic assessment of health service programs such as newborn screening so that these programs can provide better service. The Task Force on Newborn Screening addresses this responsibility in a thoughtful and comprehensive manner. The charge to the Task Force was to review and evaluate the issues and challenges facing the nation's newborn screening programs and to make recommendations to strengthen these programs. This Task Force has appropriately involved many groups and individuals from within and outside the newborn screening, pediatrics, and genetics communities, representing a diversity of views and expertise.The Task Force recommendations were developed with recognition that the environmental context within which these programs were established has changed dramatically over the past 10 years. The growing impact of consumer advocacy has resulted in a congressional directive to federal agencies to expand and evaluate newborn screening programs. New technologies such as tandem mass spectrometry and DNA-based tests offer the possibility for screening for additional conditions. Changing demographics emphasize the importance of understanding the cultural uniqueness in approaches to health. The Human Genome Project provides the basis for understanding variations in risk among individuals for medically important and genetically complex human diseases. This project brings new understandings about race and ethnicity. The advances in basic and clinical science and technology resulting from the Human Genome Project will offer unparalleled promise to improve abilities to promote health and prevent, diagnose, and treat diseases in children. Not to be forgotten will be those essential ethical, legal, and social questions that must be addressed as well as the challenge in balancing the need to both protect a population's health and to respect individual rights. Further, with the advent of new technologies and new knowledge, it is critical that the newborn screening programs continue to operate under sound public health principles and are connected to medical homes to provide care that is accessible, family-centered, continuous, comprehensive, coordinated, compassionate, and culturally competent.The task of proposing changes to meet the challenges of the 21st century, while preserving the accomplishments of the past, has been undertaken with objectivity, sensitivity, and creativity by the newborn screening, pediatric, and genetics communities. One outcome of this process is the report published here. It will provide a basis for constructive dialogue and for setting a national agenda for progress.The HRSA wishes to thank the Task Force and members of the workgroups for their hard work and their commitment to this process. We also wish to recognize the leadership that the AAP brought to the success of this process. Finally, we would like to acknowledge Linda L. McCabe, PhD, for her skillful editing of this report.

Expansion of newborn screening programs using automated tandem mass spectrometry

Expansion of newborn screening programs using automated tandem mass spectrometry