[Half a century of newborn screening in Spain: Evolution of ethical, legal and social issues (ELSIs). Part III, social issues.] / Medio siglo de cribado neonatal en España: evolución de los aspectos éticos, legales y sociales (AELS). Parte III, aspectos sociales.

Decision making for the development of newborn screening programs is based on not only medical but also social concerns and involves different stakeholders. Part III of the article focuses on their role in the governance of the programs. First of all, we consider the proactive role that health authorities has played in the evolution to an evidentiary model of policy development currently based on evidence, just as in the preparation of an expert, impartial and transparent opinion on health policy and its coordination with the national health system. And, in accordance with this evidence and with the consensus, health autorities following quality criteria have made an attempt to achieve a more homogeneous approach of the neonatal screening program throughout the territory. Secondly, we address the role of several scientific and professional societies in newborn screening. Among them, it deserves to be mentioned the Spanish Society for Clinical Chemistry, currently Spanish Society of Laboratory Medicine (SEQCML), and its Commission of inborn errors of metabolism and the Spanish Society for Newborn Screening (AECNE), which since 1985 and for thirty three years collected the activity of newborn screening centers and established a forum for debate, sharing of knowledge and cooperation among screening centers and with health authorities. Since 1999, the Spanish Society for Inborn Errors of Metabolism (AECOM) exercises an important activity in the field of diagnosis treatment and follow up of patients. Finally, we consider the role of families and the psychosocial aspects of the programme, and the associative activity of patient organizations. In 1990 the Spanish federation of PKU and other disorders (FAEPKU) was found, renamed currently as The Spanish Federation of Inherited Metabolic Diseases; together with the Spanish Federation for Rare Diseases (FEDER), found in 1999, they both have clearly contributed to the patient's empowerment, supporting research and education and establishing a network of cooperation and support for patients and their families. Patient organizations collaborate with health authorities but they have not participated in policy decision making yet. During this half century, the evolution of newborn screening programs have been characterized for a spirit of improvement, by including the development of ethical, legal and social issues. Important technological challenges lie ahead and it will be necessary to know how to use them efficiently, proportionally and fairly in the best interest of newborns and by extension of their family and society.

Las bases para la toma de decisiones acerca del desarrollo de los programas de cribado de Salud Pública no son exclusivamente médicas, sino también sociales. En esta parte III del artículo se contemplan los actores que intervienen en la gobernanza de los programas, cómo son las autoridades sanitarias, las sociedades científicas y profesionales, así como las familias y su movimiento asociativo. En primer lugar, se analiza el papel de las instituciones/autoridades sanitarias en el desarrollo de los programas y en la evolución del modelo para la toma de decisiones, hasta el actual basado en la evidencia, así como en la elaboración de una opinión experta, imparcial y transparente en política sanitaria y su coordinación en el marco del Sistema Nacional de Salud (SNS). Y, de acuerdo con dicha evidencia y con el consenso, las instituciones/autoridades sanitarias han tratado de conseguir un abordaje más homogéneo y conforme a criterios de calidad del programa de cribado neonatal en todo el territorio. A continuación, se aborda el papel de las sociedades científicas y profesionales, especialmente de la Sociedad Española de Química Clínica (actualmente Sociedad Española de Medicina de Laboratorio (SEQCML), a través de la Comisión de Errores Congénitos del Metabolismo, y de la Asociación Española de Cribado Neonatal (AECNE), que desde 1985 y durante 33 años recogieron los datos de actividad de los centros de cribado y establecieron un foro de debate, intercambio de conocimientos y colaboración entre ellos y con las autoridades sanitarias. De ellas, destaca el importante papel de la Asociación Española de Errores Congénitos del Metabolismo (AECOM) desde 1999 en el diagnóstico, seguimiento y tratamiento de los pacientes. Finalmente, se contempla el papel de las familias y los aspectos psicosociales del programa, así como la evolución del movimiento asociativo, con especial mención a la fundación en 1990 de la Federación Española de PKU y otros trastornos (FAEPKU) (que pasó después a llamarse la Federación Española de Enfermedades Metabólicas Hereditarias) y en 1999 de la Federación Española de Enfermedades Raras (FEDER). Estas asociaciones han contribuido notablemente al empoderamiento de los pacientes, a apoyar la investigación y la formación y a establecer una red de colaboración y soporte para los pacientes y sus familias. Y aunque están en contacto y colaboran con las autoridades sanitarias, hasta el momento no han participado en la elaboración de decisiones y en la gobernanza de los programas. El espíritu de superación y mejora ha marcado la evolución de los programas durante este medio siglo al incluir el desarrollo de sus aspectos éticos, legales y sociales. Se avecinan desafíos tecnológicos importantes y habrá que saber utilizarlos con eficiencia, proporcionalidad y justicia en el mejor interés del niño y, por extensión, de la familia y de la sociedad.

[Susceptibility genetics of common conditions in clinical practice]. / Des tests génétiques pour prédire des maladies communes.

The genetic tests for "non-rare thrombophilias" (TNR) were introduced into clinical setting immediately after the identification of genetic variants in the mid-90s to predict and prevent venous thromboembolism (VTE). Although being a rare example of a genetic test of susceptibility for complex diseases that has been integrated in medical routine, it is the most widespread post-natal genetics inquiry in France nowadays. Yet, determining whom to test and how to use the results is still controversial. This article outlines the trajectory of its clinical regulation and illustrates the importance of the context of use to understand its diffusion. This analysis is intended to feed a more general reflection on the issues raised by the clinical integration of genetic surveys for common diseases, particularly with regard to the clinical utility of a test (statistical vs. biological), the subjects to be tested (the case index and/or her/his relatives), and the criteria underlying access to these tests (modalities of medico-economic assessment).

TITLE: Des tests génétiques pour prédire des maladies communes. ABSTRACT: Introduit au lendemain de l'identification des « thrombophilies non rares ¼ (TNR), au milieu des années 1990 afin de prédire et de prévenir la maladie thromboembolique veineuse (MTEV), le bilan génétique pour ces thrombophilies est un exemple assez rare de test génétique de susceptibilité pour une maladie complexe, à avoir franchi le pas d'un véritable usage de routine en clinique. Bien que ce test soit le plus répandu des tests de génétique post-natale en France, son usage (À qui proposer le test ? Que faire des résultats ?) fait encore l'objet de débats. Cet article analyse la trajectoire de régulation clinique de ce test et illustre l'importance du contexte spécifique d'usage pour comprendre sa diffusion. Cette analyse vise à nourrir une réflexion plus générale sur les enjeux que pose l'intégration clinique des tests génétiques pour les maladies communes, en considérant notamment les modalités de définition de l'utilité clinique d'un test (statistique versus biologique), des sujets du test (le cas index versus ses apparentés), et des critères en sous-tendant l'accès (modalités des calculs médico-économiques).

Integrating Rules for Genomic Research, Clinical Care, Public Health Screening and DTC Testing: Creating Translational Law for Translational Genomics.

Human genomics is a translational field spanning research, clinical care, public health, and direct-to-consumer testing. However, law differs across these domains on issues including liability, consent, promoting quality of analysis and interpretation, and safeguarding privacy. Genomic activities crossing domains can thus encounter confusion and conflicts among these approaches. This paper suggests how to resolve these conflicts while protecting the rights and interests of individuals sequenced. Translational genomics requires this more translational approach to law.

introduce nationwide pulse oximetry screening for the detection of critical congenital heart disease and other hypoxaemic conditions in the newborn.

The mortality risk for infants with critical congenital heart disease (CCHD) unrecognised at the time of birth is high. Pulse oximetry has been utilised as a screening tool for the detection of these anomalies in the newborn as the majority will have a degree of hypoxaemia. This screening strategy has a moderate sensitivity and excellent specificity for the detection of CCHD, and a low false-positive rate. Respiratory and infective diseases are responsible for a large number of positive test results. The early recognition of these diseases can also improve health outcomes. Different approaches have been taken to introduce screening, ranging from hospital-led initiatives to mandatory state-wide policies. A study conducted in New Zealand demonstrated that sector-led screening initiatives are unlikely to result in equitable outcomes. In this midwifery-led maternity setting a nationwide pulse oximetry screening programme with adequate human and material resources should be introduced.

Association of US State Implementation of Newborn Screening Policies for Critical Congenital Heart Disease With Early Infant Cardiac Deaths.

IMPORTANCE: In 2011, critical congenital heart disease was added to the US Recommended Uniform Screening Panel for newborns, but whether state implementation of screening policies has been associated with infant death rates is unknown. OBJECTIVE: To assess whether there was an association between implementation of state newborn screening policies for critical congenital heart disease and infant death rates. DESIGN, SETTING, AND PARTICIPANTS: Observational study with group-level analyses. A difference-in-differences analysis was conducted using the National Center for Health Statistics' period linked birth/infant death data set files for 2007-2013 for 26 546 503 US births through June 30, 2013, aggregated by month and state of birth. EXPOSURES: State policies were classified as mandatory or nonmandatory (including voluntary policies and mandates that were not yet implemented). As of June 1, 2013, 8 states had implemented mandatory screening policies, 5 states had voluntary screening policies, and 9 states had adopted but not yet implemented mandates. MAIN OUTCOMES AND MEASURES: Numbers of early infant deaths (between 24 hours and 6 months of age) coded for critical congenital heart disease or other/unspecified congenital cardiac causes for each state-month birth cohort. RESULTS: Between 2007 and 2013, there were 2734 deaths due to critical congenital heart disease and 3967 deaths due to other/unspecified causes. Critical congenital heart disease death rates in states with mandatory screening policies were 8.0 (95% CI, 5.4-10.6) per 100 000 births (n = 37) in 2007 and 6.4 (95% CI, 2.9-9.9) per 100 000 births (n = 13) in 2013 (for births by the end of July); for other/unspecified cardiac causes, death rates were 11.7 (95% CI, 8.6-14.8) per 100 000 births in 2007 (n = 54) and 10.3 (95% CI, 5.9-14.8) per 100 000 births (n = 21) in 2013. Early infant deaths from critical congenital heart disease through December 31, 2013, decreased by 33.4% (95% CI, 10.6%-50.3%), with an absolute decline of 3.9 (95% CI, 3.6-4.1) deaths per 100 000 births after states implemented mandatory screening compared with prior periods and states without screening policies. Early infant deaths from other/unspecified cardiac causes declined by 21.4% (95% CI, 6.9%-33.7%), with an absolute decline of 3.5 (95% CI, 3.2-3.8) deaths per 100 000 births. No significant decrease was associated with nonmandatory screening policies. CONCLUSIONS AND RELEVANCE: Statewide implementation of mandatory policies for newborn screening for critical congenital heart disease was associated with a significant decrease in infant cardiac deaths between 2007 and 2013 compared with states without these policies.

Outcomes From a Hearing-Targeted Cytomegalovirus Screening Program.

BACKGROUND AND OBJECTIVES: Cytomegalovirus (CMV) is the most common congenital infection and nongenetic cause of congenital sensorineural hearing loss in the United States. Utah was the first state to pass legislation mandating CMV screening for newborns who fail newborn hearing screening (NBHS). The study objective was to present outcomes of hearing-targeted CMV screening and determine factors predicting CMV screening. METHODS: We used Utah Department of Health HiTrack and Vital Records databases to examine CMV screening from 509 infants who failed NBHS in the 24 months after implementation of the Utah legislation. Multivariate logistic regression analyses were conducted to identify predictors of compliance with CMV screening and diagnostic hearing evaluation. RESULTS: Sixty-two percent of infants who never passed hearing screening underwent CMV screening. Fourteen of 234 infants tested within 21 days were CMV positive; 6 (42.9%) had hearing loss. Seventy-seven percent of eligible infants completed a diagnostic hearing evaluation within 90 days of birth. Compliance with CMV screening was associated with sociodemographic factors, time since the law was enacted, and NBHS protocol. Infants born after the legislation showed greater odds of achieving timely diagnostic hearing evaluation than infants born before the law. CONCLUSIONS: Incorporating CMV screening into an established NBHS program is a viable option for the identification of CMV in infants failing NBHS. The addition of CMV testing can help a NBHS program attain timely audiological diagnostics within 90 days, an important early hearing detection and intervention milestone.

International differences in the evaluation of conditions for newborn bloodspot screening: a review of scientific literature and policy documents.

Despite international adoption of newborn bloodspot screening (DBS), no two countries' screening programs are the same. This article aims to understand what factors influence DBS decision-making criteria and how conditions are assessed against them. In doing so, it offers unique insights into the international landscape of DBS. A systematic review on DBS criteria in scientific literature was first undertaken. Through this, five topics were identified for consideration when analyzing DBS decision-making. Using these five topics as a template, a side-by-side comparison was conducted on DBS in policy documents of eight countries. Programs are using different approaches to explore the same policy issues, including: the beneficiary of DBS, definition of criteria, the way conditions are assessed, level of evidence required, and recommendations after assessment. These differences have the potential to result in increased disparity across DBS internationally. Ultimately, governments need to decide on their role and develop an approach to DBS decision-making in line with this role. The analyses presented in this article highlight that despite programs' commonalities, no one 'DBS decision-making solution' exists. Understanding the different approaches to decision-making within the literature and policy settings, provides an objective starting point for structured decision-making approaches for DBS programs.

Newborn screening of inherited metabolic disorders: the Italian situation.

Starting from an international overview of the current status of screening programs, the present paper focuses on the legal situation in Italy and the great differences among Italian regions. Since the introduction of tandem mass spectrometry (MS/MS) in the ‘90s the paradigm “one spot-one disease” changed. Only recently, some regions issued legislative acts to promote expanded newborn screening with MS/MS. This approach raises medico-legal and ethical issues because a fast neonatal diagnosis of an inborn error of metabolism (IEM) could increase chances of an early treatment and reduce disabilities, therefore citizens ought to have the same access to care countrywide. Enacting a mandatory standard for a disease screening panel using MS/MS and a few centers specialized in diagnosis, treatment and follow-up of patients affected by IEM (inborn errors of metabolism) can reduce legal and ethical issues.

The Use of Economic Evaluation to Inform Newborn Screening Policy Decisions: The Washington State Experience.

POLICY POINTS: Newborn screening not only saves lives but can also yield net societal economic benefit, in addition to benefits such as improved quality of life to affected individuals and families. Calculations of net economic benefit from newborn screening include the monetary equivalent of avoided deaths and reductions in costs of care for complications associated with late-diagnosed individuals minus the additional costs of screening, diagnosis, and treatment associated with prompt diagnosis. Since 2001 the Washington State Department of Health has successfully implemented an approach to conducting evidence-based economic evaluations of disorders proposed for addition to the state-mandated newborn screening panel. CONTEXT: Economic evaluations can inform policy decisions on the expansion of newborn screening panels. This article documents the use of cost-benefit models in Washington State as part of the rule-making process that resulted in the implementation of screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and 4 other metabolic disorders in 2004, cystic fibrosis (CF) in 2006, 15 other metabolic disorders in 2008, and severe combined immune deficiency (SCID) in 2014. METHODS: We reviewed Washington State Department of Health internal reports and spreadsheet models of expected net societal benefit of adding disorders to the state newborn screening panel. We summarize the assumptions and findings for 2 models (MCAD and CF) and discuss them in relation to findings in the peer-reviewed literature. FINDINGS: The MCAD model projected a benefit-cost ratio of 3.4 to 1 based on assumptions of a 20.0 percentage point reduction in infant mortality and a 13.9 percentage point reduction in serious developmental disability. The CF model projected a benefit-cost ratio of 4.0-5.4 to 1 for a discount rate of 3%-4% and a plausible range of 1-2 percentage point reductions in deaths up to age 10 years. CONCLUSIONS: The Washington State cost-benefit models of newborn screening were broadly consistent with peer-reviewed literature, and their findings of net benefit appear to be robust to uncertainty in parameters. Public health newborn screening programs can develop their own capacity to project expected costs and benefits of expansion of newborn screening panels, although it would be most efficient if this capacity were shared among programs.

AWHONN Position Statement. Newborn Screening.

The Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN) supports national minimum standards for newborn screening (NBS) programs. Federal oversight is necessary to guarantee that all pregnant women have access to appropriate counseling and that their newborns have access to timely identification of and interventions for congenital and other disorders identified through routine screening.

Whole-Genome Screening of Newborns? The Constitutional Boundaries of State Newborn Screening Programs.

State newborn screening (NBS) programs routinely screen nearly all of the 4 million newborns in the United States each year for ∼30 primary conditions and a number of secondary conditions. NBS could be on the cusp of an unprecedented expansion as a result of advances in whole-genome sequencing (WGS). As WGS becomes cheaper and easier and as our knowledge and understanding of human genetics expand, the question of whether WGS has a role to play in state NBS programs becomes increasingly relevant and complex. As geneticists and state public health officials begin to contemplate the technical and procedural details of whether WGS could benefit existing NBS programs, this is an opportune time to revisit the legal framework of state NBS programs. In this article, we examine the constitutional underpinnings of state-mandated NBS and explore the range of current state statutes and regulations that govern the programs. We consider the legal refinements that will be needed to keep state NBS programs within constitutional bounds, focusing on 2 areas of concern: consent procedures and the criteria used to select new conditions for NBS panels. We conclude by providing options for states to consider when contemplating the use of WGS for NBS.

Current status of newborn screening worldwide: 2015.

Newborn screening describes various tests that can occur during the first few hours or days of a newborn's life and have the potential for preventing severe health problems, including death. Newborn screening has evolved from a simple blood or urine screening test to a more comprehensive and complex screening system capable of detecting over 50 different conditions. While a number of papers have described various newborn screening activities around the world, including a series of papers in 2007, a comprehensive review of ongoing activities since that time has not been published. In this report, we divide the world into 5 regions (North America, Europe, Middle East and North Africa, Latin America, and Asia Pacific), assessing the current NBS situation in each region and reviewing activities that have taken place in recent years. We have also provided an extensive reference listing and summary of NBS and health data in tabular form.

[Results and lessons after 10 years of universal neonatal hearing screening in the Champagne-Ardenne region of France]. / Dépistage systématique de la surdité à la naissance : résultats et enseignements au terme de 10 ans de pratique en Champagne-Ardenne.

In France, universal newborn hearing screening has been mandatory since April23rd, 2012, but it began in the Champagne-Ardenne region on January 15th 2004. More than 99 % of 160 196 newborns have since been systematically screened in this region. Bilateral hearing impairment was thus identified in 116 infants when they were around 3.5 months old. Earlier diagnosis improves the outcome of deafness, which is only diagnosed around age 20 months without screening. The authors report their experience and the lessons learnt.

Two faces of patient advocacy: the current controversy in newborn screening.

Newborn screening programmes began in the 1960s, have traditionally been conducted without parental permission and have grown dramatically in the last decade. Whether these programmes serve patients' best interests has recently become a point of controversy. Privacy advocates, concerned that newborn screening infringes upon individual liberties, are demanding fundamental changes to these programmes. These include parental permission and limiting the research on the blood samples obtained, an agenda at odds with the viewpoints of newborn screening advocates. This essay presents the history of newborn screening in the USA, with attention to factors that have contributed to concerns about these programmes. The essay suggests that the rapid increase in the number of disorders screened for and the addition of research without either public knowledge or informed consent were critical to the development of resistance to mandatory newborn screening and research. Future newborn screening initiatives should include public education and comment to ensure continued support.

Legal considerations in cross-jurisdictional sharing of public health laboratory services.

The Centers for Disease Control and Prevention and the Association of Public Health Laboratories initiated the Laboratory Efficiencies Initiative in 2011 to help address issues related to public health laboratory (PHL) capacity to perform critically needed tests and services. One approach to improving capacity and efficiency is sharing PHL services with other states or jurisdictions. Cross-jurisdictional sharing implicates numerous federal and state laws, including federal and state privacy laws, laboratory certifications, packaging and shipping requirements for laboratory specimens, and state laws regarding fees and revenue. While federal laws generally do not present insurmountable barriers to sharing PHL services, state laws vary greatly, even within the same region of the country. This article summarizes some of the potentially relevant federal and state legal issues related to cross-jurisdictional sharing. It is important that states interested in cross-jurisdictional sharing consider all relevant laws, potential conflicts of law, as well as inconsistencies with agreements already in place among health departments and laboratories.

A comparative analysis of the governance and use of residual dried blood spots from state newborn screening programs and neonatal biobanks.

In contrast to prior research, which has focused mainly on legislative content, this study aimed to characterize the current governance structures and procedures used by state newborn screening programs in the United States regarding the research use of residual dried blood spots. Content analysis was performed on newborn screening laws, program policies, survey responses, and online material, and was compared to information from two neonatal biobanks. Important differences between newborn screening programs and neonatal biobanks included the types of permissible research with blood spots, the evaluation criteria used for research requests, and characteristics of the research proposal reviewers. These findings can inform ongoing policy conversations with respect to the governance and use of residual dried blood spots.