Currently Happening Presently Now: NEWBORN SCREENING

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Lewis, M. H., Scheurer, M. E., Green, R. C., & McGuire, A. L. (2012). Research results: preserving newborn blood samples. Science translational medicine, 4(159), 159cm12-159cm12.

Although the extent to which DBSs currently are used for biomedical research has not been fully documented, the potential impact of such research is far-reaching...Genomic information from these samples could be linked to databases with clinical information collected throughout life, which provides unprecedented opportunities to learn about health and disease physiology from the early stages of life... DBSs are an exceptional source of epigenetic information that can be used to study in utero exposure genomics and the effects of both in utero and ex utero exposures to chemicals and infectious agents. This information can be used to distinguish causal from consequential epigenetic variation....At this time, we cannot predict with any certainty exactly what the benefits of research using DBSs might be, and it may take decades before the impact of this research is fully realized. However, if these samples are destroyed we will never define the benefits that can arise from making these rare collections of biological materials available to scientists...DBSs possess value beyond their use for newborn screening. If the research community wishes to take advantage of these resources, it must advocate for policies that support the development of an infrastructure to promote the retention and use of DBSs for biomedical research.

Howell, R. R. (2006). We need expanded newborn screening. Pediatrics, 117(5), 1800-1805.

For many conditions, when newborn screening detects an abnormality that can be effectively treated, it can make the difference between a healthy life and one that requires long-term care. For this reason, the World Health Organization in 1998 recommended that newborn screening be mandatory and free of charge when early diagnosis and treatment could benefit children. Carlson recently commented that “newborn screening represents one of the major child health advances of this past century.” Those of us who have cared for infants affected with conditions for which screening has been introduced would agree heartily with this comment. Our ability to identify affected newborn infants, when totally asymptomatic, and institute programs and treatments that prevent serious morbidity and mortality is a great privilege for the pediatrician. A core of our specialty is preventive medicine, such as the practice of the careful evaluation of infants through weight and measurement in an effort to detect and treat serious underlying medical conditions.

Therrell, B. L., Johnson, A., & Williams, D. (2006). Status of newborn screening programs in the United States. Pediatrics, 117(Supplement 3), S212-S252.

Waisbren, S. E., Albers, S., Amato, S., Ampola, M., Brewster, T. G., Demmer, L., ... & Levy, H. L. (2003). Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress. Jama, 290(19), 2564-2572.

Kwon, C., & Farrell, P. M. (2000). The magnitude and challenge of false-positive newborn screening test results. Archives of pediatrics & adolescent medicine, 154(7), 714-718.

This study examined for the first time to our knowledge the national data available from newborn screening programs in the United States and determined the salient characteristics of various screening tests for 3 hereditary metabolic disorders and 2 congenital endocrinopathies with emphasis on positive predictive values (PPVs) to delineate the magnitude of false-positive results...The magnitude of false-positive results generated in newborn screening programs, particularly for congenital endocrinopathies, presents a great challenge for future improvement of this important public health program. Attention must be given to improved laboratory tests, use of more specific markers, and better risk communication for families of patients with false-positive test results.

Tarini, B. A., Christakis, D. A., & Welch, H. G. (2006). State newborn screening in the tandem mass spectrometry era: more tests, more false-positive results. Pediatrics, 118(2), 448-456.

State newborn screening programs have expanded dramatically in the past decade. Because the benefit of such testing may be unclear in some cases and because the number of infants who may receive false-positive results and may be labeled falsely as having disease is potentially sizeable, a more cautious approach is needed.

Botkin, J. R., Clayton, E. W., Fost, N. C., Burke, W., Murray, T. H., Baily, M. A., ... & Ross, L. F. (2006). Newborn screening technology: proceed with caution. Pediatrics, 117(5), 1793-1799.

The American College of Medical Genetics (ACMG) recommends a significant expansion in the number of conditions targeted by newborn screening (NBS) programs. In this commentary we advocate a more cautious approach. NBS dates to the early 1960s, when the technology developed to conduct large-scale testing on dried blood spots for phenylketonuria (PKU). PKU remains the paradigm condition for NBS because of features of the disease and its treatment, which are particularly advantageous to population screening. It is a condition that silently causes neurologic devastation but is amenable to early detection and effective prevention with a diet of moderate burden and complexity. Many children affected with PKU and their families have benefited from state screening programs over the past 4 decades because of collaboration between health departments, families, primary care providers, and metabolic specialists.

However, PKU screening is not an unmitigated success. There was initial uncertainty about whether children with variant forms of hyperphenylalaninemia required treatment and about whether affected children require life-long dietary management. Indeed, some children with benign conditions were seriously harmed from unnecessary restrictions in their diets. In addition, long-term studies demonstrate decrements in cognitive function for affected children and adolescents who are not fully adherent to the diet, yet adherence to the diet is challenging because of its poor palatability, high cost, and limits on insurance coverage in many policies. Affected women who are off the diet are at high risk of bearing severely neurologically impaired children. Only recently have many programs begun tracking affected women to enable notification, education, and management. These difficulties by no means negate the value of NBS for PKU, but they highlight the problems with the successful implementation of a population-based screening program even when a model condition is targeted.

Tang, J. L. (2005). Selection bias in meta-analyses of gene-disease associations. PLoS medicine, 2(12), e409.

Since the 1980s, meta-analysis has been widely used in summarizing results from clinical trials of medical interventions and has also recently gained increasing attention in studying gene-disease associations. However, selection bias may occur in meta-analyses due to the inability to identify and include all conducted and relevant studies. Such selection bias can cause exaggerated or even false-positive gene-disease associations. Failure to include all relevant studies is largely caused by selective publication of studies with certain results (publication bias), and the inability to identify studies published in languages other than English (language bias). Selection bias has been well recognized in meta-analyses of clinical trials. Less is known about selection bias in meta-analyses of studies of gene-disease associations; such studies generally address weak associations and thus are particularly vulnerable to biases... Selective publication can cause publication bias, which in turn could lead to false gene-disease associations in meta-analyses. It would be a disaster if a genetic screening program (in which healthy people are tested for a gene and offered a treatment if they test positive) were based on such a false association.

Almond, B. (2006). Genetic profiling of newborns: ethical and social issues. Nature Reviews Genetics, 7(1), 67-71.

Identifying genetic factors that could reliably predict health risks for individuals has the potential to bring great health benefits, both for the individuals concerned and for health-care providers. Genetic profiling at birth would allow a person's genome to be analysed at an early stage, and the data electronically stored for future use. However, although this might seem like an attractive proposition, it carries with it serious ethical and social concerns that would need to be addressed if the genetic profiling of newborns were ever to be considered on a population-wide basis.

Grosse, S. D., Rogowski, W. H., Ross, L. F., Cornel, M. C., Dondorp, W. J., & Khoury, M. J. (2009). Population screening for genetic disorders in the 21st century: evidence, economics, and ethics. Public health genomics, 13(2), 106-115.

Guttmacher, A. E., McGuire, A. L., Ponder, B., & Stefánsson, K. (2010). Personalized genomic information: preparing for the future of genetic medicine. Nature Reviews Genetics, 11(2), 161-165.

Knoppers, B. M., Sénécal, K., Borry, P., & Avard, D. (2014). Whole-Genome Sequencing in Newborn Screening Programs. Science translational medicine, 6(229), 229cm2-229cm2.

The availability of whole-genome sequencing (WGS) is likely to change the practice of population screening programs such as newborn screening (NBS). This Commentary raises key ethical, legal, and social issues surrounding WGS in NBS and suggests a need for deliberation regarding the policy challenges of introducing sequencing in such programs. Any change in the goals of NBS programs should be discussed carefully and should represent the best interests of the child.

Garver, K. L., & Garver, B. (1994). The Human Genome Project and eugenic concerns. American journal of human genetics, 54(1), 148.

Lazer, D., & Mayer‐Schönberger, V. (2006). Statutory frameworks for regulating information flows: Drawing lessons for the DNA data banks from other government data systems. The Journal of Law, Medicine & Ethics, 34(2), 366-374.

Data collection about individuals is necessary for the operation of the modern state. By the same token, the governmental collection of personal information has raised justified concerns among citizens: who within government should be able to access this information? How can and should it be used? With whom within government, and in the public (if anyone) may such personal information be shared, and under what circumstances?...The sensitivity of information is a malleable thing. What is a completely innocuous piece of information in one context may be terribly harmful in another...Genetic information is an extreme example, where data that are not interpretable today might yield great insights tomorrow. More generally, data about individuals become more powerful in the context of other data about those individuals. Digitized information can easily be separated from its original context, and injected in a different context. Moreover, technological capabilities of information processing make it enticing to re-purpose information– that is to use it for other purposes than originally intended. Why not run a victim’s fingerprints against a database of fingerprints from yet unresolved other cases? Why not use motor vehicle registration data to track people’s movements around the country over time?....While the digitization of information has made it much easier to re-purpose and re-contextualize information, the underlying problem has been with us for a long time. Take as an extreme example the effort in the 1930s by the Netherlands to redesign their population information systems. The clear purpose of this endeavor was to improve administrative efficiency. However, part of the data that they collected, for innocent reasons, was each citizen’s religious affiliation. Catastrophically, these data systems fell into the hands of the Nazis, and, arguably, as a result, Dutch Jews were killed at a much higher rate than any other Jews in Western Europe during the Holocaust. This very small amount of data collected on Dutch citizens (representable by a single bit), benign in one context, was re-purposed in deadly fashion in another context.

Anthes, E. (2009). Living Laboratories: Our digital detritus is about to launch the social sciences into the age of big data and bigger ideas. Seed. February. 81-83.

The combination of all this data with major advances in quantative analysis has spawned a social-science revolution, one that investigators say is changing the fundamental nature of research in their fields...Purpose-built technologies capable of gathering even more sophisticated kinds of information about human behavior are also entering the scene...Patterns of cell phone movement reveal the flow of people...The methods could reveal more about the state of a population than surveys and canvassing ever could.

Bowman, J. E. (1994). Genetic screening: Toward a new eugenics. It Just Ain’t Fair: The Ethics of Health Care for African-Americans. Westport, Praeger, 165-181.

Sankar, P. (1997). The proliferation and risks of government DNA databases. American journal of public health, 87(3), 336-337.

Wertz, D. C. (1998). Eugenics is alive and well: a survey of genetic professionals around the world. Science in Context, 11(3-4), 493-510.

Brase, T. (2009). Newborn genetic screening: the new eugenics. CCHC Report. April.

Pres. Counc. Bioeth. (2008). The Changing Moral Focus of Newborn Screening: An Ethical Analysis by the President's Council on Bioethics.

Roberts, D. E. (1992). Crime, race, and reproduction. Tul. L. Rev., 67, 1945.

Duster, T. (2004). Selective arrests, an ever-expanding DNA forensic database, and the specter of an early-twenty-first-century equivalent of phrenology. Tactical Biopolitics, 159.

Who could possibly be opposed to the use of these technologies for such crime-fighting purposes? The answer is a bit complex, but it has to do with some hidden social forces that create a patterned bias determining that certain populations will be more likely subjected to DNA profiling and the resuscitation of some old and dangerously regressive ideas about how to explain criminal behavior. It is now commonplace to laugh at the science of phrenology, once a widely respected and popular research program in the late nineteenth century that attempted to explain crime by measuring the shapes of the heads and faces of criminals. Yet the idea that researchers begin with a population that is incarcerated, and then use correlational data from their bodies in an attempt to explain their behavior, is very much alive and well as a theoretical and methodological strategy in the contemporary world. When researchers deploy computer-generated DNA profiles or markers and correlate them with those of people caught in the grip of the criminal justice system, the findings take on the imprimatur of the authority of human molecular genetics. Despite the oft-chanted mantra that correlation is not causation, the volatile social and political context of such correlations will require persistent vigilance and close monitoring if we are to avoid the mistakes of the past.

Rose, N. (2000). The biology of culpability: Pathological identity and crime control in a biological culture. Theoretical criminology, 4(1), 5-34.

Mark W. Leach, A Eugenics Common Sense?, Public Discourse, July 31st, 2012.

This year has seen a rash of medical studies reporting on developments in cell-free fetal DNA (cffDNA) prenatal testing. Not too long ago, one commentator cautioned that as prenatal genetic testing becomes more pervasive, our society risks developing a “eugenics common sense.” The reporting on the new cffDNA testing suggests that some have already developed this sensibility.

In October 2011, Sequenom, a publicly traded company, introduced its version of cffDNA prenatal testing. As the name suggests, floating in each expectant mother’s blood stream are bits of DNA from the child she is carrying. The new testing procedure tests this fetal DNA and can detect with the greatest reported sensitivity whether the fetus has Down syndrome. Because of false positives, cffDNA testing remains a screening-type test, providing a reassessment of the likelihood that the child has Down syndrome; it is not a diagnostic test, yet...

In his recent column for Slate—headlined “Fetal Flaw”—Will Saletan praised the advances in prenatal testing for informing mothers if they are pregnant with a “defective fetus.”..A month before Saletan’s article, Newsweek reported on the “epidemic of special needs kids.” As the charged word “epidemic” suggested, the article discussed the growing burden of caring for more children with autism and Down syndrome because of the costs of medical care. Almost lamentably, the article notes that these burdens have been somewhat compounded because, due to societal advances in medical care and inclusion in mainstream society, individuals with intellectual and developmental disabilities are now enjoying longer—and therefore costlier—lives.

Burden. Defective. Epidemic. These were terms commonly used in the eugenics era at the turn of the last century to justify compulsory sterilizations and involuntary euthanasia.

"Genetic screening is inevitable. Hysterical warnings of genocide will always be likely to fall on deaf ears in a culture, because the 'typical citizen' can hardly come to think of himself or herself as living in a society that could be so brutal in its selective extermination of a people. That was as true of the 'good Germans" in 1937 as of the 'good Americans" of 1830 who could crush human life and quell slave rebellions with Christian righteousness. The direct route to eugenics is not the issue, nor is it likely to be an issue. It is a more insidious situation about which I would issue a warning and venture a prediction. At the extremes there is a life-threatening genetic disorder, and it is not difficult to acheive a concensus about screening for it. But this is the far end of the continuum... The power of the technological advances is such that there is now a possible new attitude to be adopted - that 'the defective fetus' can be eliminated. The elimination or prevention of the 'defective fetus' is the most likely consequence and ultimate meaning of a genetic screen."
-Troy Duster, Backdoor to Eugenics, 1990, page 128.


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