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In an effort to explore new knowledge and to develop meaningful collaborations for improving child health, the First Pan African Workshop on Newborn Screening was convened in June 2019 in Rabat, Morocco. Participants included an informal network of newborn screening stakeholders from across Africa and global experts in newborn screening and sickle cell disease. Over 150 attendees, representing 20 countries, were present including 11 African countries. The agenda focused on newborn screening rationale, techniques, system development, implementation barriers, ongoing research, and collaborations both globally and across Africa. We provide an overview of the workshop and a description of the newborn screening activities in the 11 African countries represented at the workshop, with a focus on sickle cell disease.

In the past 20 years, several policy activities were undertaken that shaped today's newborn screening (NBS) programs and their associated NBS research activities: the Newborn Screening Task Force Report; the Child Health Act of 2000, Screening for Heritable Disorders; the American College of Medical Genetics and Genomics' (ACMG's) Newborn Screening Uniform Panel; and the ACMG expert panel to examine the development of a national collaborative study system for rare genetic diseases. These activities helped conceptualize the Newborn Screening Translational Research Network (NBSTRN) infrastructure and lay the foundation for its current activities. After 10 years, NBSTRN has grown into an organization that provides tools and resources for researchers to conduct research relevant to NBS programs for rare diseases for which data has been siloed locally. Infrastructure includes tools for the analytical and clinical validation of screening tests; the collection, analysis, sharing, and reporting of longitudinal laboratory and clinical data on newborn-screened individuals; and a web-based tool that allows researchers to acquire dried blood spots available for use in research from state NBS programs. NBSTRN also provides tools for researchers such as informed consent templates, disease registries, state NBS profiles, and consultation on planning pilot studies. In time, the growing data will become a resource itself.

Duchenne muscular dystrophy (DMD/Duchenne) is a progressive X-linked disease and is the most common pediatric-onset form of muscular dystrophy, affecting approximately 1:5000 live male births. DNA testing for mutations in the dystrophin gene confirms the diagnosis of this disorder. This study involves assessment of screening newborns for DMD using an immunoassay for muscle-type (MM) creatine kinase (CK) isoform&mdash, the GSP Neonatal CK-MM kit. Comparisons were made with CK activity determination by fluorescence measurement. In addition, the study evaluated the effect of gestational age, age of infant at time of sampling and how stable the CK-MM was over time. This assay discriminates well between normal, unaffected and Duchenne affected populations and is suitable for Duchenne newborn screening.

Purpose To outline structures for regional genetic services support centers that improve access to clinical genetic services. Methods A workgroup (WG) and advisory committee (AC) (1) conducted a comprehensive review of existing models for delivering health care through a regional infrastructure, especially for genetic conditions; (2) analyzed data from a needs assessment conducted by the National Coordinating Center (NCC) to determine important components of a regional genetic services support center; and (3) prioritized components of a regional genetic services support system. Results Analysis of identified priorities and existing regional systems led to development of eight models for regional genetic services support centers. A hybrid model was recommended that included an active role for patients and families, national data development and collection, promotion of efficient and quality genetic clinical practices, healthcare professional support for nongeneticists, and technical assistance to healthcare professionals. Conclusion Given the challenges in improving access to genetic services, especially for underserved populations, regional models for genetic services support centers offer an opportunity to improve access to genetic services to local populations. Although a regional model can facilitate access, some systemic issues exist—e.g., distribution of a workforce trained in genetics—that regional genetic services support centers cannot resolve.

Background Although sickle cell trait (SCT) is largely a benign carrier state, it may increase risk for certain clinical outcomes. Purpose To evaluate associations between SCT and clinical outcomes in children and adults. Data Sources English-language searches of PubMed, CINAHL, the Cochrane Library, Current Contents Connect, Scopus, and Embase (1 January 1970 to 30 June 2018) and bibliographies of review articles. Study Selection Observational controlled studies (published in English) in children or adults that examined an association between SCT and any of 24 clinical outcomes specified a priori in the following 6 categories: exertion-related injury; renal, vascular, pediatric, and surgery- or trauma-related outcomes; and overall mortality. Data Extraction A single reviewer extracted study data, which was checked by another; 2 reviewers independently assessed study quality; and strength of evidence was assessed by consensus. Data Synthesis Of 7083 screened studies, 41 met inclusion criteria. High-strength evidence supported a positive association between SCT and risk for pulmonary embolism, proteinuria, and chronic kidney disease. Moderate-strength evidence supported a positive association between SCT and exertional rhabdomyolysis and a null association between SCT and deep venous thrombosis, heart failure or cardiomyopathy, stroke, and pediatric height or weight. Absolute risks for thromboembolism and rhabdomyolysis were small. For the remaining 15 clinical outcomes, data were insufficient or strength of evidence was low. Limitation Publication bias was possible, and high-quality evidence was scant. Conclusion Sickle cell trait is a risk factor for a few adverse health outcomes, such as pulmonary embolism, kidney disease, and exertional rhabdomyolysis, but does not seem to be associated with such complications as heart failure and stroke. Insufficient data or low-strength evidence exists for most speculated complications of SCT. Primary Funding Source National Human Genome Research Institute.

In the age of genomic medicine, family health history (FHH) remains an important tool for personalized risk assessment as it can inform approaches to disease prevention and management. In primary care, including in prenatal settings, providers recognize that FHH enables them to assess the risk for birth defects and complex conditions that not only affect the fetus health, but also the mother’s. However, many providers lack the time to gather FHH or the knowledge to confidently interpret the data. Electronic tools providing clinical decision support using FHH data can aid the busy provider with data collection and interpretation. We describe the scope of conditions included in a patient-entered FHH tool that provides clinical decision support and point-of-care education to assist with patient management. This report details how we selected the conditions for which it is appropriate to use FHH as a means to promote personalized medicine in primary prenatal care.

Duchenne muscular dystrophy (DMD/Duchenne) is one of the ten most severe and common pediatric genetic diseases and affects an estimated 1 in every 5000 male births. While Duchenne is a 100% fatal disease, the clinical community has demonstrated that immediate identification and early clinical interventions can add years, even decades to an individual's life span. In anticipation of the changing therapeutic landscape for the Duchenne community, Parent Project Muscular Dystrophy established a newborn screening (NBS) initiative. This initiative included a Bioethics and Legal Issues Workgroup to consider the bioethics and legal issues of NBS for Duchenne. The workgroup's discussion focused only on Duchenne NBS and met through conference calls over a one-year period of time seeking consensus on various identified issues. This article reports on the findings and recommendations from that workgroup.

Duchenne muscular dystrophy (DMD) is the most common childhood form of muscular dystrophy, with an estimated frequency of 1:5000 live births. The impact of the disease presents as early as infancy with significant developmental delays, and ultimately loss of ambulation and respiratory insufficiency. Glucocorticoids are the only pharmacological agents known to alter the natural progression of the disease by prolonging ambulation, reducing scoliosis, and assisted ventilation. Introduction of therapy at an early age may halt the muscle pathology in DMD. In anticipation of the potentially disease-modifying products that are reaching regulatory review, Parent Project Muscular Dystrophy (PPMD) formally initiated a national Duchenne Newborn Screening (DNBS) effort in December 2014 to build public health infrastructure for newborn screening (NBS) for Duchenne in the United States. The effort includes a formalized national Duchenne Newborn Screening Steering Committee, six related Working Groups, a Duchenne Screening Test Development Project led by PerkinElmer, a program with the American College of Medical Genetic and Genomics’ Newborn Screening Translation Research Network (NBSTRN), and collaborations with other Duchenne partners and federal agencies involved in NBS. We herein review the organization and effort of the U.S. DNBS program to develop the evidence supporting the implementation of NBS for DMD.

Purpose Treatment of inherited metabolic disorders is accomplished by use of specialized diets employing medical foods and medically necessary supplements. Families seeking insurance coverage for these products express concern that coverage is often limited; the extent of this challenge is not well defined. Methods To learn about limitations in insurance coverage, parents of 305 children with inherited metabolic disorders completed a paper survey providing information about their use of medical foods, modified low-protein foods, prescribed dietary supplements, and medical feeding equipment and supplies for treatment of their child's disorder as well as details about payment sources for these products. Results Although nearly all children with inherited metabolic dis orders had medical coverage of some type, families paid “out of pocket” for all types of products. Uncovered spending was reported for 11% of families purchasing medical foods, 26% purchasing supplements, 33% of those needing medical feeding supplies, and 59% of families requiring modified low-protein foods. Forty-two percent of families using modified low-protein foods and 21% of families using medical foods reported additional treatment-related expenses of $100 or more per month for these products. Conclusion Costs of medical foods used to treat inherited metabolic disorders are not completely covered by insurance or other resources.

A trans-National Institutes of Health initiative, Nutrition and Dietary Supplement Interventions for Inborn Errors of Metabolism (NDSI-IEM), was launched in 2010 to identify gaps in knowledge regarding the safety and utility of nutritional interventions for the management of inborn errors of metabolism (IEM) that need to be filled with evidence-based research. IEM include inherited biochemical disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietary) or endogenous protein, carbohydrate, or fat. For some of these IEM, effective management depends primarily on nutritional interventions. Further research is needed to demonstrate the impact of nutritional interventions on individual health outcomes and on the psychosocial issues identified by patients and their families. A series of meetings and discussions were convened to explore the current United States’ funding and regulatory infrastructure and the challenges to the conduct of research for nutritional interventions for the management of IEM. Although the research and regulatory infrastructure are well-established, a collaborative pathway that includes the professional and advocacy rare disease community and federal regulatory and research agencies will be needed to overcome current barriers.

This report summarizes the progress made in newborn screening for Duchenne muscular dystrophy (DMD). This subject was discussed fully at a symposium held on September 11-12, 2012, in Bethesda, Maryland, by a group of experts from multiple disciplines. The meeting was triggered by the simultaneous combination of improvements in methods for newborn screening for DMD and greater potential for treatment. On the screening side, a two-tier system of newborn screening was introduced that enabled creatine kinase levels and DMD gene analysis to be done on the same dried blood spots obtained at birth. Treatment improvements included promising results from exon skipping as well as multiple studies showing long-term benefits of glucocorticoids and data indicating that early intervention of both forms of therapy was the most beneficial. Conclusions from this symposium with supportive data could have a significant impact on propelling efforts for approval of newborn screening for DMD.

In a 2012 meeting at the Centers for Disease Control and Prevention (CDC), key experts and stakeholders identified public health knowledge gaps about congenital heart defects (CHDs), namely prevalence of CHDs across the life span, long‐term outcomes of persons with CHDs, and health services

OBJECTIVE: To implement a 6-month quality improvement project in 15 primary care pediatric practices to improve short-term newborn screening (NBS) follow-up. METHODS: At the start of the project, each practice completed a survey to evaluate office systems related to NBS and completed a chart audit. Practice teams were provided information about NBS and trained in quality-improvement methods, and then implemented changes to improve care. Monthly chart audits over a 6-month period were completed to assess change. RESULTS: At baseline, almost half of practices completed assessment of infants for NBS; after 6 months, 80% of practices completed assessment of all infants. Only 2 practices documented all in-range results and shared them with parents at baseline; by completion, 10 of 15 practices documented and shared in-range results for ≥70% of infants. Use of the American College of Medical Genetics ACTion sheets, a decision support tool, increased from 1 of 15 practices at baseline to 7 of 15 at completion. CONCLUSIONS: Practices were successful in improving NBS processes, including assessment, documentation, and communication with families. Providers perceived no increase in provider time at first visit, 2- to 4-week visit, or during first contact with the family of an infant with an out-of-range result after implementation of improved processes. Primary care practices increased their use of decision support tools after the project.

f S The public health system encompasses governments, healthcare providers, and others working to improve population health. The IOM in 1988 dentified three core functions of public health: assessent, policy development, and assurance. In 1994, the Core Public Health Functions Steering Committee, which included representatives from U.S. Public Health Service agencies and other major public health organizations, developed the framework for the ten essential services for public health. This framework of generic goals nd strategies is used by public health programs and ystems to address health challenges facing the populaion or community as a whole, notably environmental azards, injuries, infections, and common chronic disases, but has also been applied to blood disorders. The papers in this supplement to theAmerican Journal of PreventiveMedicine address various facets of blood isorders and public health. Specifically, the majority of he papers focus on blood disorders that are considered are in North America or Western Europe. Because of heir rarity, rare disorders often are not considered to fall nder the purview of the public health system even hough, collectively, rare disorders do affect large numers of people. However, a public health framework is eeded to address public health services and functions for ll rare disorders, including blood disorders, regardless of he incidence or prevalence of a given disorder. The lack of a public health framework for many blood isorders, both rare and common, is a particular concern. or example, even a relatively common blood disorder uch as venous thromboembolism (VTE), with a U.S. revalence of at least 1 million people, lacks an established mechanism for surveillance. Little is definitively known about the magnitude of the public health burden of VTE. AlthoughVTE is an important cause ofmortality

Although the issue of whether sickle cell trait (SCT) is clinically benign or a significant health concern has not yet been resolved, the potential health risk to affected individuals is of vital importance and represents a tremendous challenge in protecting, promoting, and improving the health of the approximately 300 million people worldwide and 3 million people in the U.S. who possess the trait. In response to a request by the Sickle Cell Disease Association of America, in December 2009, the CDC convened a meeting of partners, stakeholders, and experts to identify the gaps in public health, clinical health services, epidemiologic research, and community-based outreach strategies and to develop an agenda for future initiatives. Through facilitated discussion and presentations in four topic areas, participants discussed pertinent issues, synthesized clinical research findings, and developed a coherent framework for establishing an agenda for future initiatives. A primary outcome of the meeting was to provide the first step of an iterative process to move toward agreement regarding appropriate counseling, care, and, potentially, treatment of people with SCT.

Sickle cell disease (SCD) is a collection of inherited blood disorders that affect a substantial number of people in the U.S., particularly African Americans. People with SCD have an abnormal type of hemoglobin, Hb S, which polymerizes when deoxygenated, causing the red blood cells to become misshapen and rigid. Individuals with SCD are at higher risk of morbidity and mortality from infections, vaso-occlusive pain crises, acute chest syndrome, and other complications. Addressing the public health needs related to SCD is an important step toward improving outcomes and maintaining health for those affected by the disorder. The objective of this study was to review public health activities focusing on SCD and define the need to address it more comprehensively from a public health perspective. We found that there has been some progress in the development of SCD-related public health activities. Such activities include establishing newborn screening (NBS) for SCD with all states currently having universal NBS programs. However, additional areas needing focus include strengthening surveillance and monitoring of disease occurrence and health outcomes, enhancing adherence to health maintenance guidelines, increasing knowledge and awareness among those affected, and improving healthcare access and utilization. These and other activities discussed in this paper can help strengthen public health efforts to address SCD.

The SACHDNC provides advice and recommendations tothe Secretary of the federal Department of Health and HumanServices (HHS) on matters concerning screening infants andchildren for inherited disorders. The SACHDNC’s charge is toadvise and guide the Secretary, HHS, regarding the most ap-propriate application of childhood and universal newbornscreening tests, technologies, policies, guidelines, and programsfor effectively reducing morbidity and mortality in newbornsand children. In addition, SACHDNC is charged to make sys-tematic evidence-based and peer-reviewed recommendationsthat include the heritable disorders, which have the potential toaffect public health significantly, for which all newborns shouldbe screened, including secondary conditions that may be iden-tified as a result of the laboratory methods used for screening.As of September 2010, SACHDNC has considered nominationsfor screening newborns for nine conditions. Formal reviews bythe Evidence Review Workgroup were conducted on six con-ditions; the remaining were considered not ready for evidencereviews. Two conditions were recommended to be added to theSACHDNC’s Recommended Uniform Screening Panel: SevereCombined Immunodeficiency (SCID) and Critical CongenitalCyanotic Heart Disease. The Secretary, HHS, accepted theaddition of SCID to the panel; the Secretary’s decision forCritical Congenital Cyanotic Heart Disease is pending.Newborn screening is an essential preventive public healthprogram that provides early identification of rare genetic, met-abolic, hormonal, and functional disorders among infants andfollow-up care for those affected. Without treatment, thescreened-for disorders can result in devastating health conse-quences and in some cases, death.

Background: Newborn screening is a complex system of interrelated multidimensional components singly focused on safeguarding the health of our nation's newborns. The long-term health outcome and well-being of individuals identified by newborn screening represents a meaningful measurement of the performance of the newborn screening system. This assessment of long-term follow-up requires a systems approach that connects stakeholders, processes, and outcomes through the collection, integration, evaluation, and sharing of key data and metrics. Methods: A review of the principles of a systems approach and its application to newborn screening long-term follow-up was performed. Past and current efforts by HRSA/MCHB that address individual components of newborn screening were assessed and utilized to outline lessons learned and suggest next steps. Results: The principle features of a systems approach applied to the creation and utilization of a health information exchange system for the long-term follow up of screen positive patients is defined. The application of this approach is in progress through the HRSA/MCHB's Effective Follow-up in Newborn Screening project. Conclusions: While several elements are in place to realize a systems approach, the authors think that the key is an integrated, multidirectional health information exchange system that functions locally, regionally and nationally, and enables information exchange between private and public health sectors.

A workshop to evaluate the reported increasing trend in the incidence rate of primary congenital hypothyroidism (CH) identified by newborn screening was held February 27 and 28, 2008, in Atlanta, Georgia, and was sponsored by the Centers for Disease Control and Prevention, the Health Resources and Services Administration, and the National Newborn Screening and Genetics Resource Center. Through a series of presentations and discussions, this group of experts considered a variety of factors that could be contributing to the perceived increasing trend of the CH-incidence rate, the gaps in knowledge that need to be overcome to identify the causes of the observed trend, and possible future research activities that might resolve the uncertainties surrounding the increasing incidence rate of CH in the United States. On the basis of these discussions, workshop participants concluded that the initial focus of future efforts should be to determine if the increasing CH-incidence rate persists once there is standardization of the diagnostic criteria for the classification of CH versus transient hypothyroidism. In discussions, workshop participants suggested that if the increasing incidence rate of CH could not be explained by definitional issues, then future research could focus on the identification and evaluation of risk factors for CH that might be changing among the US population and, thus, contributing to the observed increasing incidence rate of CH.

A variety of efforts are underway at national, state, regional, and local levels to enhance the performance of programs for early detection of inherited diseases and conditions of newborn infants. Newborn screening programs serve a vital purpose in identifying nonsymptomatic clinical conditions and enabling early intervention strategies that lessen morbidity and mortality. Currently, the programs of most intense focus are early hearing detection and intervention, using physiological techniques for audiology screening and use of newborn dried blood spots for detection of metabolites or proteins representing inherited disorders. One of the primary challenges to effective newborn screening programs to date has been the inability to provide information in a timely and easily accessible way to a variety of users. Other challenging communication issues being faced include the complexity introduced by the diversity of conditions for which testing is conducted and laboratory methods being used by each state's screening programs, lack of an electronic information infrastructure to facilitate information exchange, and variation in policies that enable access to information while protecting patient privacy and confidentiality. In this study, we address steps being taken to understand these challenges, outline progress made to date to overcome them, and provide examples of how electronic health information exchange will enhance the utility of newborn screening. It is likely that future advances in science and technology will bring many more opportunities to prevent and preempt disabilities among children through early detection programs. To take their advantage, effective communication strategies are needed among the public health, primary care practice, referral/specialty service, and consumer advocacy communities to provide continuity of information required for medical decision-making throughout prenatal, newborn, and early childhood periods of patient care.

The Secretary's Advisory Committee on Heritable Disorders in Newborns and Children is charged with evaluating conditions nominated for addition to the uniform screening panel and consequently making recommendations to the secretary of the US Department of Health and Human Services. This report describes the framework by which the committee approaches its task. Key decision nodes include initial review of every nomination to determine whether conditions are amenable for systematic evidence review, review of systematic evidence reviews conducted by the committee's external review group, and deliberation and formal recommendation for addition or exclusion to the uniform panel. Data analyzed include the accuracy and specificity of screening and diagnostic tests for nominated disorders, the extent of predicted health benefits, harms impact on disease course, and cost from early diagnosis and treatment. The committee process is guided by approaches used by similar entities, but more flexible criteria are sometimes needed to accommodate data limitations stemming from the rarity of many of these conditions. Possible outcomes of committee review range from recommendation to add a nominated condition to the uniform panel; provide feedback on specific gaps in evidence that must be addressed before making a decision; or rejection of a nomination (e.g., because of identified harms). The committee's structured evidence-based assessment of nominated conditions supports a consistently rigorous, iterative and transparent approach to its making recommendations regarding broad population-based screening programs for rare conditions in infants and children.

Newborn screening (NBS) serves as an important preventive public health program to assist families in obtaining early diagnoses, medical interventions and services for newborns affected with rare congenital conditions. Recent advances in screening techniques using tandem mass spectrometry have vastly increased the number of metabolic conditions that can be detected at birth and many NBS programs have expanded their screening panels accordingly, some now screening for more than 50 conditions. Ongoing program expansions and continuing advances in screening technology and medical care means that today, more than ever, clinicians must be fully informed about NBS. We review some of the issues impacting NBS in the USA as food for thought for clinicians faced with fulfilling their expanded role in NBS systems support. This article reviews the current status of NBS using experiences in the USA as an example of how current NBS systems are changing throughout the world. We provide information on recent publications of interest, significant policy and program issues and resources available to assist in coping with NBS advances. For clarification, we will refer to the classical form of NBS (i.e., laboratory analyses from dried blood spots) as newborn dried blood-spot screening (NDBS) and screening for congenital hearing deficiencies in newborns as newborn hearing screening (NHS). The abbreviation ‘NBS’ will be used to denote the more comprehensive integrated system that can include both NDBS and NHS. Use of the term ‘state programs’ refers to programs in the 50 US states and the District of Columbia (i.e., a total of 51 state programs nationally).

Advances in newborn screening technology, coupled with recent advances in the diagnosis and treatment of rare but serious congenital conditions that affect newborn infants, provide increased opportunities for positively affecting the lives of children and their families. These advantages also pose new challenges to primary care pediatricians, both educationally and in response to the management of affected infants. Primary care pediatricians require immediate access to clinical and diagnostic information and guidance and have a proactive role to play in supporting the performance of the newborn screening system. Primary care pediatricians must develop office policies and procedures to ensure that newborn screening is conducted and that results are transmitted to them in a timely fashion; they must also develop strategies to use should these systems fail. In addition, collaboration with local, state, and national partners is essential for promoting actions and policies that will optimize the function of the newborn screening systems and ensure that families receive the full benefit of them.

Background: The importance of family health history data in health care is widely acknowledged. Few individuals report having collected this information from their own family. Methods: This project implemented a community-based approach to design and pilot a linguistically and culturally appropriate family health history collection toolkit for two minority populations in Harrisburg, Pa. Results: The toolkit relied on oral traditions and family stories as a way to successfully introduce genetics education and family health history to these populations. Participants not only found the tool engaging and culturally appropriate, they were also able to obtain information that they were likely to share with their physician. Conclusion: While limited in scope, this project provides a model to other communities for the design, pilot testing, and implementation of a community-based public health initiative regarding family health histories.

Background/Aims: This study was performed to identify primary care physicians’ (PCPs) attitudes toward genetic medicine and their perceived needs for education in this area. Methods: Semistructured telephone interviews with 24 PCPs in the northwestern United States. Results: PCPs are interested in learning more about who should receive genetic testing and what tests are available. Training in counseling and risk communication is desired, as are ‘just-in-time’ resources to guide clinical decisions. Conclusions: PCPs are eager to learn about genetic medicine; however, their priorities may differ in emphasis from those put forward by genetics experts. Future educational efforts would do well to build on PCPs’ prior knowledge base, highlight the clinical relevance of genetic medicine to primary care practice, and emphasize ‘red flags’: cues to alert PCPs to a potential genetic contribution.

Purpose: The study purpose was to determine whether U.S. newborn screening and/or genetics programs systematically document whether newborns and their families, identified with genetic disorders through newborn dried blood spot screening, receive clinical genetic services. Methods: Nineteen state genetic plans were reviewed and a 30-question survey was administered to 53 respondents, including state newborn screening program coordinators and state genetics program coordinators in 36 states and principal investigators of 5 Health Resources and Services Administration-designated regional genetic and newborn screening collaboratives. Results: Survey findings indicate that none of the state newborn screening and/or state genetics programs routinely tracked patient-level data on clinical genetic services for newborns identified with all of the genetic and congenital conditions for which their programs screened. Few programs could provide information systematically on whether patients were referred for, or received, genetic counseling. Conclusions: Systematic tracking of clinical genetic services for newborns identified by newborn screening programs is desirable and manageable. Recent national guidelines recommend tracking genetic counseling in newborn screening follow-up. The communications processes that state programs currently use to obtain follow-up reports from subspecialists could be augmented with clinical genetic service questions. Programs should be encouraged and supported in the efforts to track genetic services for the benefit of newborns and their families.

Newborn screening (NBS) programs are population-based public health programs and are uniquely financed footline compared with many other public health programs. Since they began more than 45 years ago, the financing issues have become more complex for NBS programs. Today, almost all programs have a portion of their costs paid by fees. The fee amounts vary from program to program, with little standardization in the way they are formulated, collected, or used. We previously surveyed 37 of the 51 dried blood spot screening programs throughout the United States, and confirmed an increasing dependence on NBS fees. In this study, we have collected responses from all 51 programs (100%), including updated responses from the original 37, and updated our fee listings. Comments from those surveyed indicated that the lack of a national standardized procedural coding system for NBS contributes to billing complexities. We suggest one coding possibility for discussion and debate for such a system. Differences in Medicaid interpretations may also contribute to financing inequities across NBS programs and there may be benefit from certain clarifications at the national level. Completed survey responses accounted for few changes in the conclusions of our original survey. We confirmed that 90 percent of all NBS programs have a fee paid by parents or a third party payer. Sixty-one percent reported receiving some funds from the Maternal and Child Health Services Title V block grant, 33 percent reported some funding from state general revenue/general public health appropriations; and 24 percent reported obtaining direct reimbursement from Medicaid (without passing through a third party). A majority of programs (63%) reported budget increases between 2002 and 2005, with increases primarily from fees (72%) and to a lesser extent from Medicaid, the Title V block grant, and state general revenues.

Sickle cell disease is a group of disorders, the majority of which are detected through state newborn screening programs. There is limited knowledge of disease prevalence in the U.S. population. We report 20 years of case finding and laboratory data for sickle cell disease and trait to assist in: planning for health services delivery; providing data for researchers; aiding in tracking health outcome trends; and assessing sickle gene prevalence in the newborn population. During the 20-year period, there were 39,422 confirmed cases of sickle cell disease among 76,527,627 newborn births screened (1:1941) and 1,107,875 laboratory reports of probable sickle trait among 73,951,175 newborn births screened (1:67). The highest sickle cell disease incidence during the 20 years was in the District of Columbia (1:437) followed by Mississippi (1:683) and South Carolina (1:771). For sickle cell trait, the highest incidences were in the District of Columbia (1:22), Mississippi (1:26), and South Carolina (1:31).

The Maternal and Child Health Bureau commissioned the American College of Medical Genetics to outline a process for the standardization of outcomes and guidelines for state newborn screening programs and to define responsibilities for collecting and evaluating outcome data, including a recommended uniform panel of conditions to include in state newborn screening programs. The expert panel identified 29 conditions for which screening should be mandated. An additional 25 conditions were identified because they are part of the differential diagnosis of a condition in the core panel, they are clinically significant and revealed with screening technology but lack an efficacious treatment, or they represent incidental findings for which there is potential clinical significance. The process of identification is described, and recommendations are provided.

BACKGROUND. Financing for newborn screening is different from virtually all other public health programs. All except 5 screening programs collect fees as the primary source of program funding. A fee-based approach to financing newborn screening has been adopted by most states, to ensure consistent funding for this critical public health activity.METHODS. Two types of data are reported here, ie, primary data from a survey of 37 state public health agencies and findings from exploratory case studies from 7 states.RESULTS. Most of the programs that participated in this survey (73%) reported that their newborn screening funding increased between 2002 and 2005, typically through increased fees and to a lesser extent through Medicaid, Title V Maternal and Child Health Services Block Grant, and state general revenue funding. All of the responding states that collect fees (n = 31) use such funds to support laboratory expenses, and most (70%) finance short-term follow-up services and program management. Nearly one half (47%) finance longer-term follow-up services, case management, or family support beyond diagnosis. Other states (43%) finance genetic or nutritional counseling and formula foods or treatment.CONCLUSIONS. Regardless of the source of funds, the available evidence indicates that states are committed to maintaining their programs and securing the necessary financing for the initial screening through diagnosis. Use of federal funding is currently limited; however, pressure to provide dedicated federal funding would likely increase if national recommendations for a uniform newborn screening panel were issued.

OBJECTIVE. The purpose of this study was to measure the readability and user-friendliness (clarity, complexity, organization, appearance, and cultural appropriateness of materials) of parent education brochures on newborn screening.METHODS. We studied English-language versions of the brochures that state newborn screening programs prepare and distribute. We obtained brochures from 48 states and Puerto Rico. We evaluated each brochure for readability with the Flesch reading ease formula. User-friendliness of the brochures was assessed with an instrument we created that contained 22 specific criteria grouped into 5 categories, ie, layout, illustrations, message, manageable information, and cultural appropriateness.RESULTS. Most current newborn screening brochures should be revised to make them more readable and user-friendly for parents. Ninety-two percent of brochures were written at a reading level that is higher than the average reading level of US adults (eighth-grade level). In most brochures, the essential information for parents was buried. Although all brochures were brief and focused on the newborn screening tests being performed, 81% needed improvement in getting to the point quickly and making it easy for parents to identify what they needed to know or to do. None of the brochures scored high in all 22 criteria on the user-friendliness checklist.CONCLUSIONS. Parent education materials about newborn screening should be revised to be easier to read and more user-friendly, by lowering the reading difficulty to eighth-grade level and focusing on issues such as layout, illustrations, message, information, and cultural appropriateness. It is important that state newborn screening programs and organizations work with parents to develop and to evaluate materials to ensure that they are user-friendly.

The partnership of the Health Resources and Services Administration (HRSA)/Maternal and Child Health Bureau (MCHB) and the American Academy of Pediatrics (AAP) for improving health care for all children has long been recognized. In 1998, the establishment of the Newborn Screening Task Force marked a major initiative in addressing the needs of the newborn screening system. At the request of HRSA/MCHB, the AAP convened the task force to ensure that pediatric clinicians assumed a leadership role in examining the totality of the newborn screening system, including the necessary linkage to medical homes. The task force's report, published in 2000, outlined major recommendations for federal, state, and other national partners in addressing the identified barriers and needed enhancements of the care delivery system. Today, manifestations of the task force's recommendations are evident, many of which occurred under the leadership of HRSA/MCHB and the AAP. These activities are detailed in this article, with a discussion of future progression toward a quality, consistent, coordinated system of care for children identified with positive newborn screening results, their families, and the child health professionals who care for them.

Background: States vary widely in their use of newborn screening tests, with some mandating screening for as few as three conditions and others mandating as many as 43 conditions, including varying numbers of the 40+ conditions that can be detected by tandem mass spectrometry (MS/MS). There has been no national guidance on the best candidate conditions for newborn screening since the National Academy of Sciences report of 19751 and the United States Congress Office of Technology Assessment report of 1988,2 despite rapid developments since then in genetics, in screening technologies, and in some treatments. Objectives: In 2002, the Maternal and Child Health Bureau (MCHB) of the Health Resources and Services Administration (HRSA) of the United States Department of Health and Human Services (DHHS) commissioned the American College of Medical Genetics (ACMG) to: Conduct an analysis of the scientific literature on the effectiveness of newborn screening.Gather expert opinion to delineate the best evidence for screening for specified conditions and develop recommendations focused on newborn screening, including but not limited to the development of a uniform condition panel.Consider other components of the newborn screening system that are critical to achieving the expected outcomes in those screened. Methods: A group of experts in various areas of subspecialty medicine and primary care, health policy, law, public health, and consumers worked with a steering committee and several expert work groups, using a two-tiered approach to assess and rank conditions. A first step was developing a set of principles to guide the analysis. This was followed by developing criteria by which conditions could be evaluated, and then identifying the conditions to be evaluated. A large and broadly representative group of experts was asked to provide their opinions on the extent to which particular conditions met the selected criteria, relying on supporting evidence and references from the scientific literature. The criteria were distributed among three main categories for each condition: The availability and characteristics of the screening test;The availability and complexity of diagnostic services; andThe availability and efficacy of treatments related to the conditions. A survey process utilizing a data collection instrument was used to gather expert opinion on the conditions in the first tier of the assessment. The data collection format and survey provided the opportunity to quantify expert opinion and to obtain the views of a diverse set of interest groups (necessary due to the subjective nature of some of the criteria). Statistical analysis of data produced a score for each condition, which determined its ranking and initial placement in one of three categories (high scoring, moderately scoring, or low scoring/absence of a newborn screening test). In the second tier of these analyses, the evidence base related to each condition was assessed in depth (e.g., via systematic reviews of reference lists including MedLine, PubMed and others; books; Internet searches; professional guidelines; clinical evidence; and cost/economic evidence and modeling). The fact sheets reflecting these analyses were evaluated by at least two acknowledged experts for each condition. These experts assessed the data and the associated references related to each criterion and provided corrections where appropriate, assigned a value to the level of evidence and the quality of the studies that established the evidence base, and determined whether there were significant variances from the survey data. Survey results were subsequently realigned with the evidence obtained from the scientific literature during the second-tier analysis for all objective criteria, based on input from at least three acknowledged experts in each condition. The information from these two tiers of assessment was then considered with regard to the overriding principles and other technology or condition-specific recommendations. On the basis of this information, conditions were assigned to one of three categories as described above:Core Panel;Secondary Targets (conditions that are part of the differential diagnosis of a core panel condition.); andNot Appropriate for Newborn Screening (either no newborn screening test is available or there is poor performance with regard to multiple other evaluation criteria). ACMG also considered features of optimal newborn screening programs beyond the tests themselves by assessing the degree to which programs met certain goals (e.g., availability of educational programs, proportions of newborns screened and followed up). Assessments were based on the input of experts serving in various capacities in newborn screening programs and on 2002 data provided by the programs of the National Newborn Screening and Genetics Resource Center (NNSGRC). In addition, a brief cost-effectiveness assessment of newborn screening was conducted. Results: Uniform panel A total of 292 individuals determined to be generally representative of the regional distribution of the United States population and of areas of expertise or involvement in newborn screening provided a total of 3,949 evaluations of 84 conditions. For each condition, the responses of at least three experts in that condition were compared with those of all respondents for that condition and found to be consistent. A score of 1,200 on the data collection instrument provided a logical separation point between high scoring conditions (1,200–1,799 of a possible 2,100) and low scoring (

Newborn screening and genetic technologies are expanding and changing rapidly, increasing the demand for genetic specialty services. Because of the scarcity and geographic maldistribution of genetic specialty services, access to these services is a critical issue. This article discusses some of the efforts initiated by the Maternal and Child Health Bureau of the Health Resources and Services Administration, particularly the establishment of regional genetic and newborn screening collaboratives to improve access to these services and expertise.

While information technology has proliferated and advanced dramatically in the last 10 years, the application of information technology to health care policy and delivery has not been well coordinated either among public health agencies or between the public and private health sectors. In 1998, the Genetic Services Branch, Division of Services for Children with Special Health Needs, Maternal and Child Health Bureau, Health Resources and Services Administration (HRSA/MCHB) began an initiative to help facilitate assessment and prompt provision of appropriate services to improve the health of children. Twenty-five state public health programs received grants to improve integration of newborn screening and genetic services systems with other maternal and child health systems. All Kids Count--a program of the Public Health Informatics Institute--completed a qualitative assessment of state programs that were funded to develop plans for integration. The results are being translated into a business/policy case addressing the need for integration, a description of essential functions that such systems support, ultimately system requirements, and measures for evaluation. HRSA/MCHB's partnership with All Kids Count continues with a project to develop a community of practice to assist programs in moving their integrated child health information systems forward.

Background. As outlined in the Newborn Screening Task Force report published in August 2000, the newborn screening system is more than just testing, but also involves follow-up, diagnosis, treatment, and evaluation. As such, multiple professional and public partners need to be adequately involved in the system to help ensure success. In addition, newborn screening programs are state-based; therefore, policies and procedures vary from state to state. Historically, there has been little uniformity between state newborn screening programs.Objective. To examine the communication practices of state newborn screening programs in the United States, particularly in relation to the medical home.Methods. A facsimile survey of program staff in all US newborn screening programs. Survey data were collected in August 2000.Results. All 51 programs participated. States were questioned about whether or not they had a procedure to identify the infant’s medical home before the child’s birth. Twelve states (24%) indicated that there was a procedure in place, whereas 39 states (76%) indicated that either no procedure existed or that they were unsure. In contrast, all state programs (except 1) indicated they notified the primary care physician about abnormal results and the need for follow-up. In addition, state programs reported that primary care physicians have responsibilities within the newborn screening system, particularly related to communicating with parents about screen-positive results and coordinating the collection of a second specimen. Thirty states reported that they directly notified parents of screen-positive infants of results and the need for follow-up as well.In regard to informing parents about newborn screening, 45% of states indicated that primary care physicians had some responsibility in informing parents about newborn screening. Most often, parents were informed about newborn screening just before specimen collection, and the most commonly used techniques to educate parents were informational brochures and conversation.Thirty-five states reported that they engaged in long-term tracking of infants after diagnosis confirmation. Only about half of these states provided long-term tracking of all of the conditions included in their state’s newborn screening test panel. Of these 35 states that engaged in long-term tracking, 25 reported that they requested patient information from the primary care physician and/or subspecialist about ongoing treatment and follow-up.Conclusions. Newborn screening roles and responsibilities vary tremendously between states. Improvements in communication and better-defined protocols are needed, particularly between state newborn screening programs and the medical home. Many states identified the medical home as having significant responsibilities related to the short-term follow-up of screen-positive infants. Identification of the correct medical home before testing would help to reduce unnecessary time and frustration for state newborn screening programs, especially in the follow-up of infants that are difficult to locate. In addition, primary care physicians (ie, the medical home) need to have appropriate and ongoing involvement, including a mechanism to provide feedback to their state newborn screening program. This is particularly important given the adoption of tandem mass spectrometry by an increasing number of states, and the likely expansion of newborn screening in the future. Recommendations include the following: Primary care physicians should have appropriate and ongoing involvement in the newborn screening system and should be appropriately represented on state newborn screening advisory committees,States should develop protocols to identify the medical home before heelstick screening,States should work with families, primary care physicians, and prenatal health care professionals to develop well-defined systems for pretesting education of parents,All newborn screening results (both positive and negative) should be sent to the infant’s medical home. If results are not received by the medical home, efforts should be made to obtain results,Medical homes and subspecialists should submit follow-up information on screen-positive infants and infants with confirmed diagnoses to the state newborn screening program, regardless of the existence of state requirements to do so, andEfforts to build enhanced direct communication systems, linking state newborn screening programs to community-based medical homes, should continue.

The advent of hearing screening in newborns in many states has led to an increase in the use of genetic testing and related genetic services in the follow-up of infants with hearing loss. A significant proportion of those with congenital hearing loss have genetic etiologies underlying their hearing loss. To ensure that those identified with congenital hearing loss receive the genetic services appropriate to their conditions, the Maternal and Child Health Bureau of the Health Resources and Services Administration funded the American College of Medical Genetics to convene an expert panel to develop guidelines for the genetic evaluation of congenital hearing loss. After a brief overview of the current knowledge of hearing loss, newborn screening, and newborn hearing screening, we provide an overview of genetic services and a guideline that describes how best to ensure that patients receive appropriate genetic services. The significant contribution of genetic factors to these conditions combined with the rapid evolution of knowledge about the genetics of these conditions overlaid with the inherently multidisciplinary nature of genetic services provides an example of a condition for which a well-integrated multidisciplinary approach to care is clearly needed.

Mandated newborn screening programs for genetic and other congenital conditions for the some 4 million infants born in the United States each year have seen dramatic changes over the past decade. With the mapping of the human genome and other advances in science and technology, there will be continued challenges to and changes in these programs. Nurses who care for infants and their families should be knowledgeable about those changes to correctly transmit information to families and to participate in determining policy for newborn screening practices.

The Genetics in Primary Care (GPC) project is a USA national faculty development initiative with the goal of enhancing the training of medical students and primary care residents by developing primary care faculty expertise in genetics. Educational strategies were developed for the project by an executive committee with input from an advisory committee, comprising individuals with primary care, medical education and genetics expertise. These committees identified the key issues in genetics education for primary care as (1) considering inherited disease in the differential diagnosis of common disorders; (2) using appropriate counseling strategies for genetic testing and diagnosis, and (3) understanding the implications of a genetic diagnosis for family members. The group emphasized the importance of a primary care perspective, which suggests that the clinical utility of genetic information is greatest when it has the potential to improve health outcomes. The group also noted that clinical practice already incorporates the use of family history information, providing a basis for discussing the application of genetic concepts in primary care. Genetics and primary care experts agreed that educational efforts will be most successful if they are integrated into existing primary care teaching programs, and use a case-based teaching format that incorporates both clinical and social dimensions of genetic disorders. Three core clinical skills were identified: (1) interpreting family history; (2) recognizing the variable clinical utility of genetic information, and (3) acquiring cultural competency. Three areas of potential controversy were identified as well: (1) the role of nondirective counseling versus shared decision-making in discussions of genetic testing; (2) the intrinsic value of genetic information when it does not influence health outcomes, and (3) indications for a genetics referral. The project provides an opportunity for ongoing discussion about these important issues.

New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 Rtnol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 [tmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism.

Inborn errors of metabolism (IEM) are genetic disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietary) or endogenous protein, carbohydrate, or fat. In the U.S., many IEM are detected through state newborn screening (NBS) programs. To inform research on IEM and provide necessary resources for researchers, we are providing: tabulation of ten-year state NBS data for selected IEM detected through NBS; costs of medical foods used in the management of IEM; and an assessment of corporate policies regarding provision of nutritional interventions at no or reduced cost to individuals with IEM. The calculated IEM incidences are based on analyses of ten-year data (2001-2011) from the National Newborn Screening Information System (NNSIS). Costs to feed an average person with an IEM were approximated by determining costs to feed an individual with an IEM, minus the annual expenditure for food for an individual without an IEM. Both the incidence and costs of nutritional intervention data will be useful in future research concerning the impact of IEM disorders on families, individuals and society.

Although many types of diagnostic and carrier testing for genetic disorders have been available for decades, the use of molecular methods is a relatively recent phenomenon. Such testing has expanded the range of disorders that can be diagnosed and has enhanced the ability of clinicians to provide accurate prognostic information and institute appropriate health supervision measures. However, the proper application of these tests may be difficult because of their scientific complexity and the potential for negative, sometimes unexpected, consequences for many patients. The purposes of this subject review are to provide background information on molecular genetic tests, to describe specific testing modalities, and to discuss some of the benefits and risks specific to the pediatric population. It is likely that pediatricians will use these testing methods increasingly for their patients and will need to evaluate critically their diagnostic and prognostic implications.