Foundation of the Newborn Screening Translational Research Network and its tools for research

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.     

Newborn screening research sponsored by the NIH: From diagnostic paradigms to precision therapeutics

Newborn screening (NBS) is a successful public health initiative that effectively identifies pre-symptomatic neonates so that treatment can be initiated before the onset of irreversible morbidity and mortality. Legislation passed in 2008 has supported a system of state screening programs, educational resources, and an evidence-based review process to add conditions to a recommended universal newborn screening panel (RUSP). The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, has promoted NBS research to advance legislative goals by supporting research that will uncover fundamental mechanisms of disease, develop treatments for NBS disorders, and promote pilot studies to test implementation of new conditions. NICHD's partnerships with other federal agencies have contributed to activities that support nominations of new conditions to the RUSP. The NIH's Newborn Sequencing In Genomic Medicine and Public Health (NSIGHT) initiative funded research projects that considered how genomic sequencing could be integrated into NBS and its ethical ramifications. Recently, the workshop, “Gene Targeted Therapies: Early Diagnosis and Equitable Delivery,” has explored the possibility of expanding NBS to include genetic diagnosis and precision, gene-based therapies. Although hurdles remain to realize such a vision, broad engagement of multiple stakeholders is essential to advance genomic medicine within NBS.     

Cover Image,Volume 190, Number 2, June 2022

Cover Image: On the left upper side is the Newborn Screening Translational Research Network (NBSTRN) logo of a foot with DNA strand in the middle to depict the usual site where a newborn's sample is taken, the foot, and the DNA strand to communicate that the conditions that are screened are genetic. Across the bottom of the page is six circles to depict aspects of the newborn screening research community of (from left to right): 1) a baby in the hospital, 2) two hands hovering over two baby feet, 3) an empty circle to symbolize the invitation of new discovery through research and use of NBSTRN, 4) closeup of a baby's face, 5) a father, mother and a newborn, and 6) the DNA code spelled out in nucleotide bases of ACT and G.

     

Factors which influence the rate of receiving a routine second newborn screening test in Washington State

This study was conducted to determine whether newborns from different ethnic and socioeconomic groups in Washington State are equally likely to have a routine second newborn screening (NBS) test and if there are identifiable factors associated with not having a second test. For many years, the standard of care for NBS in Washington has been that newborns should receive a routine second screening test at age 7–10 days. However, data collected by State Department of Health (DOH) staff for the past several years indicate that only about 80% of newborns receive a routine second NBS test. The data presented here suggest that identifiable factors (i.e., barriers) exist in accessing a routine second NBS test in Washington. Increased educational efforts targeting certain high-risk infants, their parents/caretakers, and primary care providers are apparently needed to ensure equal access to a routine second test. © 1995 Wiley-Liss, Inc.     

Society of Pediatric Psychology Task Force Report: Pediatric Psychology and Injury Control

Injuries are the major causes of death for children. Pediatricpsychology offers significant contributions to the multidisciplinaryefforts necessary to prevent injuries and reduce harm to children.This Task Force Report reviews epidemiological data, characteristicsof children's injuries, passive and active interventions forreducing injuries, and research, policy, and evaluation issuesfor individual and community injury control efforts. Directionsfor future pediatric psychology efforts are identified and placedin a context of collaborative efforts required to advance thecontrol of children's injuries.     

Serum cholesterol methodology: 100 years of development

Serum cholesterol is the third nationally recommended health screening test. It is the first test which depends upon the chemical analysis of a serum compound. Over the past 100 years, the methods of measurement and methods of standardizing these measurements have improved owing to the combined efforts of clinical research, governmental and non-governmental actions, and commercial producers. The future constancy of serum cholesterol measurement will be based on: (1) National Bureau of Standards (NBS) pure cholesterol standard, (2) NBS Definitive Isotope Dilution Mass Spectrography Method, (3) Centers for Disease Control (CDC) Lipid Laboratory Reference Method, and (4) CDC National Reference System for Serum Cholesterol.     

Future Directions for Clinical Research,Services, and Training: Evidence-Based Assessment Across Informants,Cultures, and Dimensional Hierarchies

As the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) acknowledges, DSM diagnostic categories do not fit the real-world heterogeneity, comorbidity, and complexity of most mental health problems. Many efforts to develop and test evidence-based treatments also fail to take account of the heterogeneity, comorbidity, and complexity of problems seen in the community settings where most mental health services are rendered. Most community services cannot attain the treatment specificity and fidelity characterizing randomized controlled trials, which often yield larger therapeutic effects than when the tested treatments are tried in community services. Widely applicable evidence-based assessments (EBAs) can bridge gaps between evidence-based treatments and the diverse providers, cases, and conditions characterizing community services. To advance community services, intake EBAs can help providers take account of cross-informant discrepancies, parents’ problems, multicultural variations, and hierarchical dimensional aspects of psychopathology. To capitalize on intake EBAs, progress and outcome EBAs should be used to identify changes and failures-to-change on which to base recalibrations of treatments. To strengthen therapeutic alliances, the results of intake, progress, and outcome EBAs can be shared with parents. To bridge gaps between research and services, it is recommended that training in clinical research and services should (a) focus on widely applicable EBAs as essential foundations for evidence-based practice; (b) systematically promote intake, progress, and outcome EBAs; and (c) equip psychologists to advance evidence-based practice in community services. To implement these recommendations, research is needed on how to increase use of EBAs, organize services around routine use of EBAs, and help providers base service decisions on EBAs.     

Waiving informed consent in newborn screening research: balancing social value and respect

While newborn screening (NBS) programs have historically relied on presumptive benefit in deciding when to implement new tests, experience has demonstrated that this approach can lead to screening tests that lack efficacy or, worse yet, cause harm. Population-based NBS research provides an opportunity to evaluate safety and effectiveness of potential tests prior to widespread implementation. Using the example of Pompe disease, we argue that waiving the requirement for informed consent is appropriate for research evaluating the screening phase of potential NBS tests when data support the potential health benefits of testing and when other research safeguards are present. The regulatory requirement for informed consent can be waived if a research study meets criteria of minimal risk, protecting rights and welfare, and practicability. In population-based NBS research, the main risks are related to false positive results and results with ambiguous implications for treatment-risks that are comparable to those posed by many tests newly added to NBS programs without prior population-based NBS research. Waiving the informed consent requirement facilitates the development of flexible strategies for informing and educating parents about NBS research that reflect the logistics of population-based NBS screening. A strict interpretation of the regulatory requirement of informed consent may create significant logistical and financial barriers to adequate evaluation of NBS tests. Without a broader interpretation of this regulatory requirement in NBS research for which there is evidence of a clinically meaningful benefit from treatment, we may create incentives for the implementation of inadequately evaluated NBS tests.     

Military-related PTSD and intimate relationships: From description to theory-driven research and intervention development

Military operations in Iraq and Afghanistan have brought heightened awareness of military related PTSD, as well as the intimate relationship problems that accompany the disorder and can influence the course of veterans' trauma recovery. In this paper, we review recent research that documents the association between PTSD and intimate relationship problems in the most recent cohort of returning veterans and also synthesize research on prior eras of veterans and their intimate relationships in order to inform future research and treatment efforts with recently returned veterans and their families. We highlight the need for more theoretically-driven research that can account for the likely reciprocally causal association between PTSD and intimate relationship problems to advance understanding and inform prevention and treatment efforts for veterans and their families. Future research directions are offered to advance this field of study.     

The need for unity in the biomedical research community

The author provides a perspective on how basic scientists view contemporary issues of biomedical research funding by discussing five topics of concern to the biomedical research community and the need for that community to form a new consensus as the basis for new approaches to legislative efforts in Congress and communication with the public. The topics are (1) the reasons scientific societies became active in legislative efforts in Congress, (2) the reasons there was initial friction between these societies and other institutions in the biomedical research community, (3) the history of the founding of a biomedical research community, (3) the history of the founding of a biomedical research caucus in the House of Representatives, (4) the effects of the Institute of Medicine's recent report on funding health sciences research, and (5) the weakness of the present institutional coalition. The author proposes specific steps to develop a more unified approach to achieve a common biomedical research agenda.     

A latent change score approach to understanding dynamic autonomic coordination

Children's self-regulation is a core adaptive system in child development. Physiological indices of regulation, particularly the autonomic nervous system (ANS), have garnered increased attention as an informative level of analysis in regulation research. Cardiography supports the simultaneous examination of both ANS branches via measures of pre-ejection period (PEP) and respiratory sinus arrhythmia (RSA) as indicators of sympathetic and parasympathetic activity, respectively. However, despite their heavily intertwined functions, research examining autonomic coordination across sympathetic and parasympathetic systems is scarce. Moreover, extant efforts have favored static, mean level reactivity analyses, despite the dynamic nature of ANS regulation and the availability of analytic tools that can model these processes across time. This study drew on a sample of 198 six-year-old children from a diverse community sample (49.5% female, 43.9% Latinx) to examine dynamic autonomic coordination using bivariate latent change score modeling to evaluate bidirectional influences of sympathetic and parasympathetic activity over the course of a challenging puzzle completion task. Results indicated that children evidenced reciprocal sympathetic activation (i.e., PEP attenuation and RSA withdrawal) across the challenge task, and these regulatory responses were characterized by a temporally leading influence of PEP on lagging changes in RSA. The current findings contribute to our understanding of children's autonomic coordination while illustrating a novel analytic technique to advance ongoing efforts to understand the etiology and developmental significance of children's physiological self-regulation.     

Exploring existing and deliberated community perspectives of newborn screening: informing the development of state and national policy standards in newborn screening and the use of dried blood spots

Objective

Since the 1960s newborn screening (NBS) for several rare and serious disorders has been in place across Australia. Testing of a simple blood spot now enables the early detection of over 30 conditions. Policies across Australian states have diverged in some aspects of NBS, especially in the retention and further use of dried blood spots collected as part of the screening and attempts are underway to bring some further national consistency. Whilst this has initiated debate amongst health professionals and policy makers there is limited empirical evidence of wider community attitudes to such issues.

Methods

This research has explored the range and depth of views held by the wider community in New South Wales through moderated small group discussions. It has also assessed the range and depth of responses where the groups are reconvened after being given further information.

Results

The findings suggest that there is limited community awareness of the public health importance of NBS and especially that resulting biological samples are stored. Members of the wider community presented with opportunities to consider current procedures and policies appear reassured and to have high levels of trust. However there are clearly some groups who have concerns with the storage of dried blood spot specimens and perceive that these may be abused.

Policy implications and conclusion

The findings will inform health professionals and policy makers as to the perceived benefits and future challenges NBS raises for the wider community. The findings have implications for improving current communications about NBS, maintaining public confidence and the development of state and national initiatives in genetic health.

     

Application of health behaviour theory to sleep health improvement

Although sleep hygiene is often used for broad sleep health promotion efforts, sleep hygiene education programmes are largely ineffective. These programmes are limited by their lack of a theoretical foundation. Health behaviour theory (HBT) has been used for decades to successfully predict and modify many health behaviours, but its use in the study of sleep health is rare. The purpose of this review is threefold. First, four dominant HBTs will be introduced. Second, the brief literature on HBT and sleep health will be reviewed. Lastly, a translational research agenda will be proposed. The present review concludes that HBT shows potential in both the prediction and modification of sleep health, and that there are several short‐ and long‐ term research goals to advance these efforts.     

A case report of a patient with microcephaly, facial dysmorphism, chromosomal radiosensitivity and telomere length alterations closely resembling "Nijmegen breakage syndrome" phenotype

Genetic heterogeneity in Nijmegen breakage syndrome (NBS) is highlighted by patients showing clinical and cellular features of NBS but with no mutations in NBS1 and normal levels of nibrin. NBS is an autosomal recessive disorder, whose clinical cellular signs include growth and developmental defects, dysmorphic facies, immunodeficiency, cancer predisposition, chromosomal instability and radiosensitivity. NBS is caused by mutations in the NBS1 gene, whose product is part of the MRE11/RAD50/NBS1 complex involved in the DNA double-strand break (DSB) response pathway. Since the identification of the NBS1 gene, patients with NBS clinical signs, particularly severe congenital microcephaly, are screened for mutations in the NBS1 gene. Further analyses include X-ray-induced chromosome aberrations, telomere analysis, kinetics of DSBs repair, levels of a panel of proteins involved in the maintenance of genetic stability, radiation-induced phosphorylation of various substrates and cell cycle analysis. We describe a patient with a NBS clinical phenotype, chromosomal sensitivity to X-rays but without mutations in the whole NBS1 or in the Cernunnos gene. Enhanced response to irradiation was mediated neither by DSBs rejoining defects nor by the NBS/AT-dependent DNA-damage response pathway. Notably, we found that primary fibroblasts from this patient displayed telomere length alterations. Cross-talk between pathways controlling response to DSBs and those involved in maintaining telomeres has been shown in the present patient. Dissecting the cellular phenotype of radiosensitive NBS-like patients represents a useful tool for the research of new genes involved in the cellular response to DSBs.     

Hybrid Research Models: Natural Opportunities for Examining Mental Health in Context

The articles in this series promote hybrid research models to bridge the gap between efficacy and effectiveness. We suggest that efforts such as those described in these articles are long overdue. Given the enormous public health consequences of the lack of available and effective mental health services, we no longer can afford research that neglects the natural state of affairs or that leaves others to translate research into practice. It is time to acknowledge that the process of testing interventions in the university for transfer to the community is neither efficient nor empirically justified. Guided by the articles in this series, we focus on the ways in which hybrid models can provide natural opportunities to advance the field and lead to a new generation of research that is both contextually relevant and methodologically rigorous. An iterative process of research and practice is proposed that can lead to stronger theories and methods and enhanced understanding of mental health in context.     

Attitudes of genetic counselors towards expanding newborn screening and offering predictive genetic testing to children

There is movement to expand newborn screening (NBS) to include conditions that challenge the traditional public health screening criteria. Little is known about the attitudes of genetic counselors towards expanding NBS and offering predictive genetic tests to children. For our study genetic counselors completed an internet survey posted on the National Society of Genetic Counselors Listserv regarding five conditions: cystic fibrosis (CF), Duchenne muscular dystrophy (DMD), glucose-6-phosphate dehydrogenase deficiency (G6PD), fragile X (FraX), and type 1 diabetes (T1D). The survey addressed attitudes towards: (1) testing high-risk infants; (2) mandatory NBS; (3) population screening beyond the newborn period; and (4) testing one's own child. Two hundred sixty-seven usable surveys were received. Over two-thirds of respondents supported testing high-risk infants for all conditions except T1D (22%). CF was the only condition for which there was majority support for both mandatory NBS (56%) and later population screening (60%). For all other conditions, later population screening was preferred over NBS (P 相似文献   

Measuring social capital: An exploration in community–research partnership

Large numbers of social policy initiatives and community organizations are currently engaged in “community building” efforts that seek, in part, to strengthen informal relationships and the organizational infrastructure of communities and to build the capacity of communities to manage and foster community change. One critical requirement for improving such practice is for communities to have greater access and capacity to use information for planning, advocacy, and assessment. There are, however, a number of challenges to this, especially as it concerns understanding complex, sometimes elusive, dimensions of community circumstances and dynamics—the level of community “social capital,” for example—that are of central interest to those involved in community‐building efforts. The authors describe what was learned through a community–research partnership that attempted to test practical options for community‐based organizations (CBOs) to measure aspects of community social capital for their own purposes and within the constraints of budget, time, and skills under which they work. © 2006 Wiley Periodicals, Inc.     

Newborn screening for mucopolysaccharidoses: opinions of patients and their families

We have conducted a study to assess the opinions of parents of individuals with mucopolysaccharidoses (MPS) and adults with MPS regarding newborn screening (NBS) for this condition, as testing is now technically possible. A questionnaire including a number of hypothetical clinical scenarios about NBS for MPS was distributed to members of MPS support groups from United States and Australia. Questionnaires were returned by 249 members of the US (40% response) and Australian (38% response) support groups. Eleven respondents were adults with MPS and the rest were parents of individuals with MPS. Eighty-six percent of respondents indicated that they would have wanted NBS for their own children. Ninety-seven percent supported the use of NBS for MPS in situations where early treatment that favorably impacts on disease outcome is available, 87% supported NBS when a severe form of MPS was diagnosed, but no treatment is available that improves the long-term outcome and 84% supported NBS for mild MPS where no disease-modifying treatment is available. The most common reason cited in support of NBS was that NBS could avoid a delay in diagnosis and the accompanying distress that delayed diagnosis created. This study has identified strong support for the introduction of NBS for MPS from this group. Psychosocial benefits of screening may outweigh potential harms.     

Duchenne expert physician perspectives on Duchenne newborn screening and early Duchenne care

Duchenne muscular dystrophy (DMD) is a progressive, fatal neuromuscular disorder typically diagnosed between 4 and 5 years of age. DMD currently has five FDA approved therapies, which has led to increased interest in newborn screening (NBS) for DMD. Our objective was to explore the perspectives and predicted practices of physicians (primarily neurologists) who will likely be responsible for the follow-up of infants identified with DMD through NBS. A short survey was developed and distributed to physicians who are responsible for providing care for patients with Duchenne at Certified Duchenne Care Centers across the USA. Twenty-seven physicians responded to statements about benefit and readiness for dystrophinopathy NBS, which care recommendations they would make at initial infant visits, and when they would recommend initiating approved therapies. Most DMD physicians indicated they see benefit in NBS (82%) and believe the DMD care community is ready for NBS in dystrophinopathies (74%). The majority of physicians would recommend multiple interventions, including genetic counseling, maternal carrier testing, referral to early intervention services, screening siblings, discussion of clinical trials, exon skipping therapies, and assessment of social and language development at initial visits. The majority of physicians also indicated they would recommend initiating approved therapies much earlier than the typical age of diagnosis.