Natasha Bonhomme

The impact of false-positive newborn screening results on families: a qualitative study

Purpose:Newborn screening leads to improved treatment and disease outcomes, but false-positive newborn screening results may cause distress for parents. The purpose of this study was to describe the experiences of families who receive a false-positive newborn screening result in an attempt to discover ways to help improve the newborn screening communication process for families.Methods:This was a qualitative study using two methods of data collection: in-depth, semistructured interviews and focus groups. Participants (N = 27) were parents whose children (ages 6–16 months) underwent follow-up testing after newborn screening and whose follow-up test results indicated that the newborn screening result was a false-positive.Results:Our analysis found that parents who have a false-positive newborn screening result experience five distinct stages. Most parents did not report long-term negative impacts of the experience, but some experienced some residual worry. Participants described effective provider communication as key in mitigating stress. Some parents identified the experience as leading to positive outcomes.Conclusion:Identifying best practices for communication between the health care providers and parents is an essential component in improving the newborn screening process. Further research is needed to discover best practices for communication to minimize potential harm and maximize the benefits of newborn screening.Genet Med 2012:14(1):76–80

Parental Permission for Pilot Newborn Screening Research: Guidelines From the NBSTRN

There is broad recognition of the need for population-based research to assess the safety and efficacy of newborn screening (NBS) for conditions that are not on current panels. However, prospective population-based research poses significant ethical, regulatory, and logistical challenges. In the context of NBS, there have been a variety of approaches that address parental decision-making in pilot studies of new screening tests or conditions. This article presents an ethical and legal analysis of the role of parental permission by the Bioethics and Legal Work Group of the Newborn Screening Translational Research Network created under a contract from the National Institute of Child Health and Human Development to the American College of Medical Genetics and Genomics. Circumstances are outlined in which a waiver of documentation of permission or a waiver of permission may be ethically and legally appropriate in the NBS context. These guidelines do not constitute American Academy of Pediatrics policy.

Implications of Newborn Screening for Nurses

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

APPLaUD: access for patients and participants to individual level uninterpreted genomic data.

BackgroundThere is a growing support for the stance that patients and research participants should have better and easier access to their raw (uninterpreted) genomic sequence data in both clinical and research contexts.Main bodyWe review legal frameworks and literature on the benefits, risks, and practical barriers of providing individuals access to their data. We also survey genomic sequencing initiatives that provide or plan to provide individual access. Many patients and research participants expect to be able to access their health and genomic data. Individuals have a legal right to access their genomic data in some countries and contexts. Moreover, increasing numbers of participatory research projects, direct-to-consumer genetic testing companies, and now major national sequencing initiatives grant individuals access to their genomic sequence data upon request.ConclusionDrawing on current practice and regulatory analysis, we outline legal, ethical, and practical guidance for genomic sequencing initiatives seeking to offer interested patients and participants access to their raw genomic data.

Nothing about us without us: guidelines for genetic testing.

Guidelines for genetic testing developed by professional societies may be more centered on the concerns of society members than the needs of the individuals and families that may undergo testing. This could be considered appropriate because it will be the healthcare provider who will assess whether to test; when to test; whom to test; and how to provide the right support, interpretation, and follow-up to the individual or family tested. Genetic testing requires guidelines because of the complexity of testing for the individual and his or her family. It also requires flexibility because context matters a great deal in genetics. For this very reason, multiple stakeholders should be involved in guideline development. Professional societies have a deliberative process for their members, and those closely associated with their practice, to engage in discourse that leads to guidelines. We believe that the testing guidelines should reflect more than the professionals’ perspective. Ultimately, the ramifications of testing guidelines do not exist in isolation from the whole healthcare experience of the individual. This means that the perspectives of other providers, the individuals, and families should be a part of the deliberative process. One might ask why the advocacy organizations don’t establish guidelines themselves. We believe that multiple stakeholder groups should be involved. A striking example of where two groups of professionals create difficulties for each other and the people they serve is the guidelines for spinal muscular atrophy (SMA) carrier screening. Obstetricians disagree with geneticists about carrier testing for this condition. Geneticists believe that carrier testing for SMA should be offered to the general population, and obstetricians do not believe it should be offered broadly. In statements made by the two societies, the contrast is clear, but from the point of view of the patient, it is confusing. The American College of Obstetricians and Gynecologists’ Committee on Genetics concludes: ‘‘[The committee] agrees that preconception and prenatal screening for SMA is not recommended in the general population at this time’’ (American College of Obstetricians and Gynecologists, 2009). The American College of Medical Genetics, on the other hand, concludes: ‘‘Because SMA is present in all populations, carrier testing should be offered to all couples regardless of race or ethnicity. Ideally, the testing should be offered before conception or early in pregnancy. The primary goal is to allow carriers to make informed reproductive choices’’ (Prior 2008). As a result of these two guidelines, obstetricians, midwives, geneticists, nurses, nurse practitioners, pediatricians, genetic counselors, and potential parents do not have a clear guideline on which to base a decision. It does not appear that either professional society engaged the other stakeholders from the ‘‘medical home’’ to any great degree, particularly in the guideline articulation. It is not apparent that either society invited the very individuals whose lives are affected by the decision into the process of creating guidelines. This case of SMA carrier screening is also a good example because of the complexity of the issue for parents as well. There are parents of children with SMA who desperately wish carrier screening had been available to them before they had to witness their baby die of the condition. There are also parents of children with the condition, albeit a milder form, who are very concerned that carrier screening might limit the number of children born with the condition. This might decrease appreciation for these children and perhaps reduce research activity and funding for the condition. The American College of Medical Genetics recently released guidelines for genetic testing in children (American College of Medical Genetics, 2013). This is a revision of a statement they made more than 10 years ago, so it was a welcome addition to current considerations for all of the stakeholders. It is not apparent that the deliberative process included parents of children affected by genetic conditions. It did not include advocates of the various disease advocacy organizations. Although it would be much more difficult to come to consensus with multiple stakeholders, doing so is a worthy endeavor. The silos that exist in medicine, from basic discovery through translational science to delivery of services, severely limit progress. The learning healthcare system (Institute of Medicine, 2011) requires that all stakeholders be involved in the entire process. Starting with clinical questions emerging from clinical care and the lived experience of individuals and families with disease will help accelerate diagnostic and treatment development. Engaging clinicians (of all specialties) and citizens in formulating basic research plans will help to make discovery more relevant to translational science. Empowering communities, whether geographic, ethnic, or disease affinities, to be responsible for characterizing cohorts will stitch together a national clinical research network of engaged communities (Seifer S, 2013). Learning from the people who

Newborn Screening: Adapting to Advancements in Whole-Genome Sequencing

September is newborn screening awareness month. Since 1963, state public health programs have screened newborns for a number of life-altering health conditions. Many of these disorders are rare and genetic, and if caught in the first weeks of life they can be treated or managed to prevent death or a lifetime of disability. Early detection can also help families avoid the lengthy and stressful “diagnostic odyssey” involved in finding out what ails their child (Exe et al.). In 2013, the United States celebrated the 50th anniversary of newborn screening. From scientist Robert Guthries discovery of a test for phenylketonuria to development of state programs that screen every newborn for up to 56 conditions, newborn screening has saved and improved millions of lives. State-mandated screening gives newborns their best chance for typical development, in large part because of strong national guidelines and efficient state public health systems that have been evolving to support screening for the last 50 years. n nAs newborn screening success stories gained national notoriety in the early 1960s, scientists quickly discovered diagnostic tests for a host of genetic disorders that could be treated at birth. State public health officials then responded by developing mandatory screening programs with inclusion of increasing numbers of genetic and metabolic conditions. While testing every newborn at birth is a seemingly simple process, organizing the resources required for obtaining samples, analyzing results, diagnosing disorders, and providing follow-up care is a large undertaking for state public health systems. n nSince its inception, the newborn screening program has seen continued improvement. Creation of the International Society for Neonatal Screening in 1988 and the signing of the Newborn Screening Saves Lives Act of 2008 are examples of initiatives to increase education and funding for newborn screening in an effort to adapt to new discoveries and methods for treating rare or genetic diseases. Recently, the cost of whole-genome and whole-exome sequencing has decreased dramatically, emphasizing the potential for genome sequencing to affect newborn screening programs. Newborn screening policymakers and stakeholders must respond to these advancements as they have responded to others in the past, recognizing that while some technological updates have a place in the newborn screening system, others may not. As public health officials work to come to a conclusion on whole-genome sequencing for newborns, it is important to keep the interests of families and children at the forefront of the discussion. n nIn June 2014, a geneticist sequenced his sons genome at birth, making the child one of just a few thousand healthy newborns in the United States who have undergone this type of testing (Regalado, 2014). Inova Translational Research Institute is also offering newborn genome sequencing as a part of their Childhood Longitudinal Cohort Study, which looks to learn about disease by tracking 2500 children in Fairfax County, Virginia, from pregnancy to age 2 years (Inova Translational Medical Institute, 2014). The press surrounding both the fathers controversial decision and Inovas study highlights the evolving debate over whether whole-genome or -exome sequencing for healthy newborns has a place in public health screening programs. Currently in newborn screening programs across the country, whole-genome sequencing is used only as a secondary method to confirm positive test results for genetic disorders such as cystic fibrosis or sickle cell disease, but experts have suggested that in the next decade large-scale sequencing for all healthy babies at birth could be plausible (Knoppers et al., 2014). As of this writing, the American College of Medical Genetics and Genomics had not yet released an official position on genome sequencing for newborns, although they have presented preliminary guidelines for genome sequencing and its clinical application in adults and children. n nIt is important when discussing potential updates to newborn screening programs to keep the typical parent with minimal genetic testing experience in mind. Goldenberg and colleagues did just this in 2014, surveying parent opinion of whole-genome sequencing for newborns if it were offered by newborn screening programs or pediatrician services. In both scenarios, about 70% of parents expressed interest in whole-genome sequencing, citing test accuracy and the ability to protect a child from developing a disease as important factors in their decision-making process (Goldenberg et al., 2014). In addition to confirming preliminary parent interest in whole-genome sequencing, research has determined that genome sequencing may be less costly and faster than conventional newborn screening processes, with the ability to produce results in 50 hours rather than the typical 4–6 weeks (Saunders et al., 2012). Lower cost and shorter time to results could be beneficial in lessening public health costs and parent anxiety; however, the possibility of learning a childs susceptibility to more than 3000 diseases, some adult-onset and some without cures, presents a daunting ethical and public health concern to policymakers. n nWhile genome sequencing has the potential to detect disease and improve health outcomes, an assessment of its impact on individuals, families, and overall health is needed before public health programs could ever implement official clinical whole-genome sequencing for newborns. Responding to this need for large-scale evaluation of newborn genome and exome sequencing, the National Institutes of Health awarded

Is this a genesis in prenatal testing: genomic knowledge, risk or benefit?

25 million over 5 years under the Genomic Sequencing and Newborn Screening Disorders program to four grantees, with the goal of exploring the use of genomic sequencing in newborn healthcare, in the fall of 2013 (National Institutes of Health, 2013). The grantees for 2013 are implementing studies to explore best practices for delivering sequencing results to parents, as well as looking at the law, policy, and ethics of newborn exome and genome sequencing. Outcomes of these earliest large-scale assessments of the risks and benefits of genome sequencing for newborns will help to inform newborn screening policy for the future, but today the topic of newborn genome sequencing as a public health initiative remains contentious. n nIs whole-genome sequencing of newborns best left to the private sector of health? Newborn screening is a highly successful public health program, and addition of whole-genome sequencing would require a complete overhaul of a system that has saved millions of lives. Private-sector whole-genome sequencing at birth instead puts the ethical and financial burden of interpreting results primarily on new parents, private practice genetic counselors, and nongovernment labs. Before whole-genome sequencing could ever be of value to newborn screening programs and families, public health initiatives would need to create an infrastructure that could properly support whole-genome sequencing outcomes. It may also be prudent while considering whole-genome sequencing of newborns to simultaneously improve prenatal screening and carrier testing protocols. Although generally not included in public health–based screening, prenatal testing for genetic disorders gives parents who choose any of the many tests available ample time to consider their options and prepare for a child who could be born with health challenges. Carrier screening identifies the likelihood of offspring having a genetic disorder before conception and during the prenatal period. For both, the ethical implications and clinical outcomes are more clearly defined than those for whole-genome sequencing. Increased public health initiatives for prenatal testing and carrier screening have the potential to drastically reduce the incidence of infants born with genetic disorders and also better prepare parents for the outcomes of their pregnancies. n nRegardless of where newborn whole-genome sequencing ends up within the health sector, policymakers need to tackle challenges, such as storing vast amounts of sequence data securely, developing genetic counseling techniques to advise new parents, and establishing ethical standards for the practice as a whole. These challenges also apply to prenatal and carrier testing initiatives. The public health community must decide whether the benefits of adding whole-genome sequencing to well-established newborn screening programs outweigh the associated ethical pitfalls, while also preparing to educate families about the option of whole-genome sequencing for their newborn.

'Your DNA, Your Say': global survey gathering attitudes toward genomics: design, delivery and methods

Ten fingers and ten toes was all that used to matter. Now in the genomic era, we have more to go on than just digits. It is theoretically possible for expectant parents to receive the whole genome sequence of the fetus in the course of prenatal screening. This has been done by using cell-free DNA in maternal plasma at 18.5 weeks with the saliva of the father (Kitzman et al., 2012). Current methods of invasive prenatal testing detect aneuploidies and specifically targeted mutations. This new technology has the ability to also identify de novo mutations—genetic variations that have not occurred in either parent—without harming mother or fetus. Kitzman et al. identified 39 of 44 de novo mutations (Kitzman et al., 2012). As a result, a fetus can be screened for more than approximately 3000 single-gene disorders (a number that is increasing), potentially leading to a diagnosis. These tests can provide information about prenatal, newborn, childhood, and late-onset diseases. The cataloging of variation in the individual’s genome can offer everything from diagnostic information with high clinical utility to an indication of future risk. Knowledge about multigene diseases, epigenetics, and mutations in the human genome is emerging. Obtaining a whole genome sequence reveals a vast amount of data for which interpretation is currently limited. However, our knowledge, analysis, and applications of the genome will become more accurate and clinically relevant over time. Information garnered from such tests can offer families information to make informed choices. Because this information affects whole families and society overall, parents, clinicians, ethicists, and policymakers will grapple with difficult ethical and policy decisions—including what information should be revealed, to whom, and when. It is speculated that, as time goes on, noninvasive prenatal testing, which will be potentially less risky than invasive screening, will become more widely used (Hayden, 2012). The implications of this knowledge for the family over time are the central consideration. There are at least two major ethical considerations: the autonomy of the individual and diversity of the human population. Currently, society grants full autonomy to an individual at age 18 years. Ideally, an individual would decide at this point to learn about later-onset genetic conditions and predispositions. Noninvasive prenatal testing could disclose information about the child 18 years earlier than the age of full autonomy. Although this situation is not unique to the utilization of genetic technologies, it may be more likely to arise in the decisions involved in family planning and parenting in the near future. Although these tests have the goal of improving early detection of genetic conditions, the ways in which these new technologies are used can alter the genetic and societal fabric of the human family, potentially diminishing its diversity. Noninvasive procedures that pose no risk to the developing fetus may continue to normalize prenatal testing and increase utilization. In many cases, this is very useful information. However, there is some concern that information that was previously unavailable in this period has the potential to increase terminations due to aneuploidies, minor abnormalities, and potentially even nonmedical traits (de Jong et al., 2010). It may evolve that the use of prenatal testing will align with parental preferences rather than primarily consider the wellbeing of the child and the life that they could lead regardless of a genetic abnormality. With the increased use of such a powerful technology, it is important to consider unintended consequences. Would the technology usher in a world without genetic disability and disease? What would this mean for individuals in our society who are currently living with disabilities? Would fewer resources be allocated to treating and curing these conditions? All people, whether affected by disease or disability, play an important role in our society. No human is perfect; the ‘‘imperfections’’ that can or cannot be decoded from our genome are what makes each human an individual. As technology and scientific understanding about the human genome increase, so does the prevalence of ethical dilemmas in society. Sensationalized stories of designer babies and futuristic societies of clones have instilled fear in the public about the potential uses of the human genome. Some dismiss this fear as invalid because cloning and designer babies are not the goal of these tests, nor are they currently possible. Designer babies or a modern-day eugenics movement may be byproducts of emerging technology if we do not fully explore the ethical questions raised by new technologies before they are widely adopted. The public must be educated about genetics and its applications in medicine and society. Advances in prenatal testing and

Including ELSI research questions in newborn screening pilot studies

Our international study, Your DNA, Your Say, uses film and an online cross-sectional survey to gather public attitudes toward the donation, access and sharing of DNA information. We describe the methodological approach used to create an engaging and bespoke survey, suitable for translation into many different languages. We address some of the particular challenges in designing a survey on the subject of genomics. In order to understand the significance of a genomic result, researchers and clinicians alike use external databases containing DNA and medical information from thousands of people. We ask how publics would like their anonymous data to be used (or not to be used) and whether they are concerned by the potential risks of reidentification; the results will be used to inform policy.

Newborn Screening and Health Communications

BackgroundThe evidence review processes for adding new conditions to state newborn screening (NBS) panels rely on data from pilot studies aimed at assessing the potential benefits and harms of screening. However, the consideration of ethical, legal, and social implications (ELSI) of screening within this research has been limited. This paper outlines important ELSI issues related to newborn screening policy and practices as a resource to help researchers integrate ELSI into NBS pilot studies.ApproachMembers of the Bioethics and Legal Workgroup for the Newborn Screening Translational Research Network facilitated a series of professional and public discussions aimed at engaging NBS stakeholders to identify important existing and emerging ELSI challenges accompanying NBS.ResultsThrough these engagement activities, we identified a set of key ELSI questions related to (1) the types of results parents may receive through newborn screening and (2) the initiation and implementation of NBS for a condition within the NBS system.ConclusionIntegrating ELSI questions into pilot studies will help NBS programs to better understand the potential impact of screening for a new condition on newborns and families, and make crucial policy decisions aimed at maximized benefits and mitigating the potential negative medical or social implications of screening.