The Changing Moral Focus of Newborn Screening: An Ethical Analysis by the President's Council on Bioethics
The President's Council on Bioethics
Newborn screening in the United States today is a complex public health endeavor that touches the lives of nearly every one of the four million babies born in the country each year. In this chapter we offer an account of the basic features of newborn screening as it is practiced in the United States. We first trace the origins and describe the current practice of newborn screening, noting some of the challenging aspects of it that raise ethical questions. Then, we briefly describe the state and federal policies pertaining to the practice of newborn screening.
I. The Practice of Newborn Screening
Screening is a public health initiative that surveys an entire population (or sub-population) for evidence of an illness before it exhibits symptoms. The purpose of screening is to identify those among the apparently well who are suffering from (or who will likely develop) a disease and who are likely to benefit from early detection and intervention.1 Because screening is applied to the healthy and the sick alike, the screening assay must be both sensitive—it should identify all or almost all cases of disease—and specific—it should minimize the number of false positives, i.e., of healthy individuals who are incorrectly identified as having the disease. When screening for rare disorders in large populations, it is all but inevitable that some healthy individuals will initially test positive for the disease. Because of this problem of false positives, screening programs typically require follow-up testing to confirm or deny the initial result.
As practiced in the United States, newborn screening is almost entirely genetic screening.2 That is, the illnesses targeted are heritable disorders that are caused by abnormalities in the individual's genes and chromosomes.3 Newborn screening is applied to the entire population shortly after birth. Genetic screening at other stages of life is also possible, but is generally practiced more selectively when there is a perceived need. For example, preimplantation genetic diagnosis (PGD) involves screening human embryos before transfer to a woman's uterus after in vitro fertilization; prenatal screening (e.g., by amniocentesis) looks for genetic defects in the fetus prior to birth; post-infancy screening is applied to children in the years after birth; carrier screening (at any stage of life, but especially in prospective parents) is used to identify healthy people who carry one copy of a defective gene that, if present in two copies, would cause an illness.4
Newborn screening began in the United States in the early 1960s after American microbiologist Robert Guthrie developed a test for phenylketonuria (PKU), an inborn error of metabolism that, if left untreated, causes severe mental retardation. Guthrie's simple, sensitive test for PKU required absorbing a drop of the infant's blood on a piece of filter paper. During the 1960s most states passed laws requiring that a drop of blood be drawn after pricking the heel of each infant at birth, so that the blood could be analyzed for evidence of PKU. The rationale for mandatory PKU screening was that affected infants could suffer devastating neurological damage if there were even a few weeks of delay in starting them on a low-phenylalanine diet. Afterwards, other diseases that also could be detected in that blood spot were added to the state screening programs: galactosemia (GALT), maple syrup urine disease (MSUD), and homocystinuria (HCY) in the late 1960s, congenital hypothyroidism (CH) in the 1970s, and sickle cell disease (SCD) in the 1980s. Over the years, newborn screening has steadily expanded so that today, depending on the state, an infant born in the United States is likely to be screened for somewhere between twenty-nine and fifty-four conditions.
The practice of newborn screening varies from state to state; there is no unified systematic approach at the national level. However, since 1985, the Council of Regional Networks for Genetic Services (CORN) has endeavored to provide public health services with an overall framework for a systems approach to newborn screening.5 Ideally, an effective newborn screening program includes the following elements: education, screening, follow-up and diagnosis, treatment, and evaluation.
An effective newborn screening program must ensure that medical professionals, parents, and the general public are adequately informed about newborn screening and the heritable disorders that it targets. Educating parents about newborn screening is a challenge that will only grow with the increasing number and complexity of the disorders for which babies in the future will be screened. Typically, for prospective parents a state publishes an informative brochure that attempts to educate them about what newborn screening is and what consequences it may have for their child.6 The obstetrician may discuss newborn screening with the parents sometime late in the third trimester, in the course of preparing them for what will happen at the hospital when their baby is born.7 Yet, as studies have shown, most parents are only vaguely aware that their newborns are being screened, even after the drawing of blood; they are even less aware of the particular conditions for which screening is carried out:
Very rarely did parents say they sought or received information about newborn screening before their infant was born. Many recalled receiving a newborn screening brochure in a packet of information given to them during the hospital stay after delivery; very few, however, reported reading it or remembering the information in the brochure. Even fewer actually recalled being told anything about newborn screening while in the hospital. If they were told anything, it was that their infant had a “blood test.” “The hospital visit was a fog; the only thing I wanted to know was ‘is the baby OK?'”8
The fact that parents of newborns are generally ignorant about newborn screening is hardly surprising. The birth of a child is a momentous and exhausting experience for parents; so much is going on in the first minutes and hours after birth that the drawing of a drop of blood from the infant's heel is not likely to loom large in the parents' minds as a significant event. From the moment of birth the newborn baby is constantly being evaluated, beginning with the Apgar scores (recorded at one minute and five minutes after birth) that assess the baby's skin color, heart rate, reflexes, muscle tone, and breathing. The baby is also being measured, washed, and given eye drops to prevent infection, a vaccine against hepatitis B, and a vitamin K shot to improve clotting. Sometime before the baby leaves the hospital (usually between twenty-four and ninety-six hours after birth), the heel is pricked and a few droplets of blood are squeezed out and absorbed onto a piece of filter paper, and that is the last that most parents will hear about genetic screening of their infant, unless a positive result is reported for one of the assays.9
The specimen of the baby's blood is sent to a laboratory, where concentrations of specific chemical compounds are measured and compared with the normal ranges expected for healthy babies. Within the last five years, most screening laboratories in the United States have begun to use a technology called tandem mass spectrometry (MS/MS) as the principal tool for analyzing newborn blood samples. MS/MS has made the screening process easier because it is a “multiplex testing platform,” i.e., it can be used to screen at once for over forty of the “inborn errors of metabolism” that comprise a large majority of the conditions targeted by newborn screening. These metabolic disorders detected by MS/MS can be separated into three categories: fatty acid disorders, amino acid disorders, and organic acid disorders.
Fatty acid disorders are caused by deficiencies in the enzymes that help the body derive energy from fat. Fat must be used as a source of energy when the body runs out of glucose, the principal source of energy production. If blood glucose levels are depleted and the body is unable to metabolize fat, the cells of the body suffer an energy crisis, which can lead to lethargy, coma, or death. Fatty acid disorders may also result in excessive fat buildup in the liver, heart, and kidneys, causing a variety of symptoms, including liver failure, encephalopathy (diseases of the brain), heart and eye complications, and problems with muscle development. Two examples of fatty acid disorders are medium-chain acyl-CoA dehydrogenase deficiency (MCAD) and very long-chain acyl-CoA dehydrogenase deficiency (VLCAD).
Amino acid disorders are caused by one of two sorts of enzyme deficiencies: either a failure of the enzymes needed to break down certain amino acids, or a failure of the enzymes needed to rid the body of ammonia (a by-product of amino acid metabolism) by way of the urea cycle. The buildup of amino acids or ammonia in the blood can cause severe medical complications, including mental retardation, developmental delays, failure to thrive, and death. Two examples of amino acid disorders are PKU and MSUD.
Organic acid disorders involve deficiencies in the enzymes that normally help in the breakdown of amino acids (as well as, in some cases, lipids and sugars). When these substances are not broken down, toxins accumulate in the body. The enzyme deficiencies are farther down the pathways of amino acid metabolism, so there is not a buildup of amino acids but of certain organic acid intermediates. Infants with these disorders are usually well at birth, but may soon develop poor feeding, irritability, lethargy, vomiting, and other symptoms, including coma or death. Some of these disorders have later onset or milder symptoms. Two examples of organic acid disorders are isovaleric acidemia (IVA) and glutaric acidemia type 1 (GA1).10
Before MS/MS was introduced for newborn screening, a separate assay was needed for each condition. Now only endocrine disorders (e.g., CH), hemoglobin disorders (e.g., SCD), and a few others require different screening platforms.11
MS/MS employs two mass spectrometers, which are analytical instruments that weigh the molecules present in a minute sample. A mass spectrometer can determine exactly what kinds of molecules are present in the sample and in exactly what concentrations. In MS/MS, the two mass spectrometers are connected together by a chamber called a collision cell. The collision cell's job is to break up the molecules after one of the mass spectrometers has weighed and sorted them. The other mass spectrometer then sorts and weighs the pieces of the molecules that are of interest to those conducting the screening.
In newborn screening, the molecules whose concentrations are measured by MS/MS include amino acids (abnormal levels of which indicate an amino acid disorder) and acylcarnitines (abnormal levels of which indicate a fatty acid or organic acid disorder). Tandem mass spectrometry is the most reliable, widely available method for measuring these compounds in a child's blood.12
Recent studies have shown that MS/MS also can be used to detect a class of genetic conditions known as lysosomal storage disorders, including the rare Fabry, Gaucher, Krabbe, Niemann-Pick, and Pompe diseases. Because clearly efficacious treatments are not yet available for the lysosomal storage disorders, assays for these conditions have not been included in most MS/MS newborn screening panels. New York is one exception; children born there are routinely screened for Krabbe disease.13
C. Follow-up and Diagnosis
Abnormal screening results are reported to the newborn's primary care physician or pediatrician, who communicates them to the parents. How the results of newborn screening are reported varies from state to state. Most states report abnormal results to the birth hospital by letter, fax, phone call, or lab report. Norma l results are also usually reported to the birth hospital, though sometimes also to the pediatrician or the parents.14 Most of the time, abnormal results are reported within a week after the screening.
It is, however, important to recognize that an initial positive screening result is not the same as a diagnosis of disease. If for any reason the reliability of the initial screening result is questionable, a repeat test may be ordered. Even if the screening result is considered reliable, the possibility of false positives means that more detailed confirmatory testing (sometimes involving DNA analysis or other quantitative methods) will be required before a definitive diagnosis is reached. With rare exceptions, when treatment for a detected disorder is available, it is not started until after the diagnosis is confirmed. In the meantime, the parents will receive counseling about the possible implications of the positive result, while the newborn is referred to the appropriate health care providers for proper medical evaluation, confirmatory testing, diagnosis, and treatment.
The problem of false positives deserves further comment. In detecting rare genetic disorders by analyzing metabolites in the blood a serious dilemma is encountered. If the presence of a disorder is signaled by an abnormally high level of a certain metabolite in the infant's blood, exactly how high does the level have to be in order to judge that the infant has tested positive for the disorder? Set the threshold level too high, and a certain number of infants who actually have the disorder will go undetected; these are called false negatives. Set the level too low, and most or all infants with the disorder will be detected, but many additional infants will test positive without actually having the disorder. The rate of such false positives has been considerably reduced with the introduction of MS/MS and other precise testing platforms. Such screening protocols are extremely sensitive (i.e., they successfully identify the vast majority of infants actually suffering the disorder) while being at the same time extremely specific (i.e., the vast majority of positive results are true positives, not false positives). Unfortunately when a population is screened for extremely rare disorders, even a highly specific and sensitive assay can yield very large numbers of false positives.15
As a result, for many of the conditions that most states screen for, a large majority of the initially positive screening results will turn out to be incorrect. For instance, in 2007, 3,364,612 infants were tested for MSUD in the United States. Of those tested, 1,249 were initially reported back as testing positive, but only eighteen newborns were eventually confirmed, after further testing, as having the disease16 The other 1,231 out of 1,249 positive results turned out to be false.17 Pediatrician Beth Tarini and colleagues have calculated that the screening of all American newborns for metabolic disorders by MS/MS is likely to yield some tens of thousands of false positive results per year.18
Such high rates of false positives may be an unfortunate but unavoidable side effect of trying to identify every infant with a rare genetic disorder. Concerns have been raised, however, about the potential impact of false positive screening results on parental anxiety and stress, parent-child relationships, and perceptions of the child's health,19 and there is always the risk that a child incorrectly identified as suffering from a genetic disorder will be given inappropriate treatment before further testing establishes that the initial screening result was false. In Chapter Three, we shall return to the problem of false positives in our discussion of ethical issues raised by the expansion of newborn screening. For our present purposes, it is sufficient to note that the great majority of initially positive results are, on further testing, shown to be inaccurate. And the rarer the disease targeted by newborn screening, the more likely it is for screening to produce a multitude of false positives for every true positive result.
D. Treatment and Evaluation
Newborns confirmed to have a genetic disease need to be referred to metabolic specialists, endocrinologists, hematologists, or pulmonologists who will be responsible for developing a specific plan for the care and treatment of the child. In many cases, disease management will continue throughout the affected child's life. For a few serious genetic diseases, the treatment is simple, inexpensive, effective, and relatively unobtrusive. Thus, for the one in 4,000 children suffering from congenital hypothyroidism, a daily thyroxin tablet makes possible a normal life instead of a grim future of growth failure and permanent mental retardation. For other disorders, the treatment is difficult but manageable. Thus children diagnosed with PKU can grow up free of its devastating neurological symptoms by maintaining a diet low in phenylalanine for the rest of their lives. This course of treatment is effective but quite burdensome, as it entails severely restricting (or eliminating) the eating of high-phenylalanine foods such as breast milk, meat, chicken, fish, nuts, cheese, and legumes.
For certain other detectable genetic disorders, as we shall see, the prognosis is much less clear, and the appropriate course of treatment is not known with certainty. Moreover, even when a treatment is “available,” many other steps have to be taken to realize the treatment's benefits for the affected children. Not only must the diagnosis be confirmed, but resources must be effectively and consistently delivered to the child and family over a long period of time. In some cases, state newborn screening programs may adequately fund the detection of genetic disorders without ensuring that affected infants receive adequate long-term care.20 For example, children found to have SCD are supposed to take a daily prophylactic dose of the antibiotic penicillin, through at least the age of five, in order to prevent life-threatening bouts of pneumonia and other infections. Most states have been screening newborns for SCD since the 1980s, and each year about 2,000 new cases are detected, chiefly among African-American infants; but a 2003 study revealed that children affected with SCD received, on average, only forty percent of the recommended medication (i.e., the mean number of days of the year that an affected child received the antibiotic was only 148).21 Clearly, success at identifying infants with the disease does not guarantee that children are truly benefiting from newborn screening for SCD; yet SCD screening is a well-established program and is widely considered one of the more successful examples of mandatory newborn screening.22
Finally, to establish that a certain newborn screening program is truly effective, rigorous evidence-based studies are needed to find out whether early detection and intervention produce a truly positive outcome for the affected infants. Yet, all too often, diseases are added to mandatory screening panels without adequate pilot studies establishing the efficacy of detection and intervention, and then without adequate follow-up studies evaluating all the long-term consequences, both good and bad, for the children identified by the program. In 1992, Norma n Fost examined the unintended consequences of the screening programs for PKU and sickle cell anemia, among other illnesses, and drew an important general lesson: that screening asymptomatic individuals for genetic abnormalities is not simply a neutral gathering of information with no effect on the lives of those screened; instead, every screening program must be considered an experiment until the benefits and risks have been clarified by well-designed empirical studies.23 In Chapter Two of this white paper, we return to this question of the efficacy of newborn screening as we examine the expansion in state-mandated newborn screening programs that is occurring today.
II. Public Policy and Newborn Screening
Both federal and state governments make policy governing newborn screening, but the federal government has so far played a comparatively limited role in shaping screening programs. It offers grants to help states pay for screening costs and research.24 It has working committees designed to explore the ethical, social, clinical, and political implications of newborn screening.25 It ensures that laboratories processing the screening tests meet strict standards.26 It approves screening platforms for public use,27 as well as the labeling and advertising of screening platforms.28
The state governments play a much larger role in shaping screening programs. Each state chooses the screening platforms that will be used within its jurisdiction. Each state chooses the panel of conditions for which newborns will be screened. Each state is responsible for ensuring that every newborn within its borders at least has the opportunity to be screened. Finally, each state pays most of the costs of the screening process (in most cases by collecting fees to cover the expense).29
Although the states have virtually unlimited freedom to determine how to organize and conduct their own screening programs, many states have at least a few similar policies. For example, many states have privacy and confidentiality policies to protect personal information, including genetic information. Many states allow the parents to opt out of the screening. And many states have education programs that provide parents with information on the screening process, such as the conditions being screened for, a description of the conditions, the manner of the collection procedure, and an explanation of why the health care professionals might need to retest.30
Just as there are important similarities among the programs, there are also some differences. One of the main differences is in the quality of parental education. Many states do not provide parents with information on the accuracy of screening, the possibility of false positives, when the results of the screening tests will be available, the privacy and confidentiality laws governing the information obtained, or how the parents might decline the offer for screening. The states also differ in the fees charged for newborn screening. Some states charge no fee at all, while other states charge as much as $140.31 Still another difference is in the number of initial screening tests required, with some states requiring only one test to be conducted and other states requiring two initial tests.32
Of particular significance—especially for the purposes of this white paper—is the fact that almost all the states have substantially increased the number of conditions targeted by their newborn screening programs. Until the advent of MS/MS, most states screened newborns for only a handful of conditions. Yet today, every state screens for or will soon be screening for at least thirty conditions, and some states screen for as many as fifty-seven.33 Many of these conditions were added to state screening panels in the past few years, in response to recommendations issued in 2005 by the American College of Medical Genetics (ACMG). In the next chapter we turn to a detailed analysis of the ACMG's newborn screening recommendations and the ethical issues they raise.
1. Screening of populations is different from testing of individuals; an individual patient who exhibits certain symptoms of illness will typically undergo diagnostic testing to ascertain the cause and the severity of the illness.
2. On similarities and differences between genetic and non-genetic testing, see Michael J. Green and Jeffrey R. Botkin, “‘Genetic Exceptionalism' in Medicine: Clarifying the Differences between Genetic and Nongenetic Tests,” Annals of Internal Medicine 138 (2003): 571-575.
3. A few states also screen newborns for infectious diseases: Massachusetts and New Hampshire screen infants for toxoplasmosis. Connecticut, Illinois, and New York screen for HIV; Connecticut and Illinois do so only if the mother was not tested for HIV during pregnancy. See the National Newborn Screening and Genetic Resources Center 's “National Newborn Screening Status Report,” (November 10, 2008, version), available online at http://genes-r-us.uthscsa.edu/nbsdisorders.pdf.
4. For example, couples of Eastern European Jewish descent who are contemplating marriage and childbearing may prospectively undergo carrier screening for Tay-Sachs disease, an invariably fatal genetic disorder that will affect about a quarter of their children if both parents are carriers of the defective gene.
5. See Bradford L. Therrell, et al., “ U.S. Newborn Screening System Guidelines: Statement of the Council of Regional Networks for Genetic Services (CORN),” Screening 1 (1992): 135-147; Kenneth A. Pass, et al., “US Newborn Screening System Guidelines II: Follow-Up of Children, Diagnosis, Management, and Evaluation. Statement of the Council of Regional Networks for Genetic Services (CORN),” Journal of Pediatrics 137 (2000): S1-S46; and American Academy of Pediatrics, “Serving the Family From Birth to the Medical Home. Newborn Screening: A Blueprint for the Future,” Pediatrics 106 (2000): 389-422.
6. See Bradford L. Therrell, et al., “Status of Newborn Screening Programs in the United States,” Pediatrics 117 (2006): S212-S252, Table 3, “Responses to Survey of Processes Related to State/Territorial Newborn Screening Information Brochures,” pp. S218-S219; and Kathryn E. Fant, et al., “Completeness and Complexity of Information Available to Parents from Newborn-Screening Programs,” Pediatrics 115 (2005): 1268-1272.
7. See Ellen W. Clayton, “Talking With Parents Before Newborn Screening,” Journal of Pediatrics 147 (2005): S26-S29.
8. Terry C. Davis, et al., “Recommendations for Effective Newborn Screening Communication: Results of Focus Groups With Parents, Providers, and Experts,” Pediatrics 117 (2006): S326-S334.
9. Some states require that infants be screened a second time, some days or weeks after birth, though most states require repeat screening only if the initial screening was performed less than twenty-four hours after birth. The purpose of such repeat screening is to catch disorders that for a variety of reasons might not show up in blood samples taken so soon after birth.
10. See the National Newborn Screening and Genetics Resource Center at http://genes-r-us.uthscsa.edu/ for more information on these conditions.
11. The hemoglobinopathies are detected by one of two other multiplex testing platforms: either high pressure liquid chromatography (HPLC) or isoelectric focusing (IEF). Besides CH and congenital adrenal hyperplasia (CAH), the disorders that require separate assay platforms (“singletons”) include congenital hearing loss, biotinidase deficiency (BIOT), cystic fibrosis (CF), and GALT.
12. American College of Medical Genetics/American Society of Human Genetics Test and Technology Transfer Committee Working Group, “Tandem Mass Spectrometry in Newborn Screening,” Genetics in Medicine 2 (2000): 267-269; Sandra Banta-Wright and Robert Steiner, “Tandem Mass Spectrometry in Newborn Screening, A Primer of Neonatal and Perinatal Nurses,” Journal of Perinatal and Neonatal Nursing 1 (2004): 41-58; and Donald Chace, “A Layperson's Guide to Tandem Mass Spectrometry and Newborn Screening,” online at www.savebabies.org.
13. See Michael Gelb, et al., “Direct Multiplex Assay of Enzymes in Dried Blood Spots by Tandem Mass Spectrometr y for the Newborn Screening of Lysosomal Storage Disorders,” Journal of Inheritable Metabolic Disease 29 (2006): 397-404; Yijun Li, et al., “Direct Multiplex Assay of Lysosomal Enzymes in Dried Blood Spots for Newborn Screening,” Clinical Chemistry 50 (2004): 1785-1796; and David Millington, “Newborn Screening for Lysosomal Storage Disorders,” Clinical Chemistry 51 (2008): 808-809.
14. See Franklin Desposito, et al., “Survey of Pediatrician Practices in Retrieving Statewide Authorized Newborn Screening Results,” Pediatrics 108 (2001): E22; and Kenneth D. Mandl, et al., “Newborn Screening Program Practices in the United States : Notification, Research, and Consent,” Pediatrics 109 (2002): 269-273.
15. To understand the problem of false positives, one has to consider not only the sensitivity and specificity of a screening protocol but also its positive predictive value, which is defined as the proportion of patients with positive test results who are correctly diagnosed. Even if sensitivity and specificity are high, positive predictive value can be quite low when the disease is very rare (i.e., when the prevalence of the disease is very low.) If PPV = positive predictive value, Se = sensitivity, Sp = specificity, and P = prevalence, it can be shown that
Even more simply, if TP = true positives and FP = false positives, since
, it follows that the ratio of false positives to true positives is
These formulae mean that, no matter how high the test specificity (as long as it is not 100 percent), a sufficiently rare disease (i.e., low prevalence P ) can make the positive predictive value of a test extremely low and the ratio of false positive results to true positive results correspondingly high.
16. Data downloaded from the National Newborn Screening Information System, available online at www2.uthscsa.edu/nnsis.
17.With sixty-eight false positives for every true positive detected, and an estimated prevalence of one in 180,000, newborn screening for MSUD in 2007 had a positive predictive value of about 1.4 percent, which would be consistent with a sensitivity approaching 100 percent and a specificity as high as 99.96 percent. This shows vividly how an extraordinarily sensitive and specific test can nonetheless yield high numbers of false positives if the targeted condition is exceedingly rare. See Andreas Schulze, et al., “Expanded Newborn Screening for Inborn Errors of Metabolism by Electrospray Ionization-Tandem Mass Spectrometry: Results, Outcome, and Implications,” Pediatrics 111 (2003): 1399-1406.
18. Beth Tarini, et al., “State Newborn Screening in the Tandem Mass Spectrometry Era: More Tests, More False-Positive Results,” Pediatrics 118 (2006): 448-456. They calculated a best-case scenario of 2,575 false positives per year, and a worst-case scenario of 51,059 false positives per year, but this was for the year 2005, before most states had implemented the ACMG's expanded screening panel.
19.See, for example, Elizabeth Gurian, et al., “Expanded Newborn Screening for Biochemical Disorders: The Effect of a False-Positive Result,” Pediatrics 6 (2006): 1915-1921. The psychosocial impact of false positive screening results will be explored further in Chapter Three.
20. See Celia I. Kaye, et al., “Assuring Clinical Genetic Services for Newborns Identified Through U.S. Newborn Screening Programs,” Genetics in Medicine 9 (2007): 518-527.
21. Colin M. Sox, et al., “Provision of Pneumococcal Prophylaxis for Publicly Insured Children with Sickle Cell Disease,” Journal of the American Medical Association 290 (2003): 1057-1061. As for why the children do not receive proper medication, Sox and his colleagues wrote the following: “Reasons for such poor provision of prophylactic medication are unknown, but may include physicians not writing prescriptions for prophylactic antibiotics or patients not taking written prescriptions to the pharmacy. Notably, children frequently interacted with the health care system, with a mean of 13 outpatient encounters per year, suggesting ample missed opportunities to emphasize and assess compliance with prophylaxis.” (Ibid., p. 1060.)
22. Richard S. Olney, “Preventing Morbidity and Mortality from Sickle Cell Disease: A Public Health Perspective,” American Journal of Preventive Medicine 16 (1999): 116-121.
23. Norma n Fost, “Ethical Implications of Screening Asymptomatic Individuals,” FASEB (Federation of American Societies for Experimental Biology) Journal 6 (1992): 2813-2817, p. 2814.
24. Section 300b-8 of Title 42 of the United States Code states that the Secretary of the Department of Health and Human Services (HHS) must award grants to entities to improve state and local health agencies' ability to provide screening, counseling, or health care services to newborns and children who have or are at risk for heritable disorders. See also Sections 300b-1, 300b-6, and 300b-9 for more details on the federal government's role.
25. Section 300b-10 of Title 42 states that the Secretary must establish the “Advisory Committee on Heritable Disorders in Newborns and Children.” The Committee is to offer advice to the Secretary on grants awarded under Sec. 300b-8.
26. The Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), which improved upon the Clinical Laboratory Improvement Act of 1967 (CLIA-67), is the law that permits the Secretary of HHS to create quality standards for laboratory testing. Laboratories can choose to receive CLIA certification either by an appropriate state agency or by an approved private organization, such as the Joint Commission on Accreditation of Healthcare Organizations, the College of American Pathologists, or the American Society for Histocompatibility and Immunogenetics. HHS, through the Centers for Medicare and Medicaid (CMS), published most of the regulations pertaining to CLIA in 1992.
At the time CLIA-88 was enacted and its regulations formulated, MS/MS was just becoming available and the Human Genome Project was just beginning. Much in genetics and genetic testing has changed since then. So while genetic testing laboratories are still subject to CLIA-88, some have argued that the law offers very little guidance regarding genetic testing. As far back as 1997, the National Institutes of Health-Department of Energy Task Force on Genetic Testing issued a report ( Promoting Safe and Effective Genetic Testing in the United States ) calling for the HHS Clinical Laboratory Improvement Advisory Committee (CLIAC) to recommend the creation of a subspecialty on genetics in order to address this shortcoming of CLIA-88. CLIAC then proposed some changes to the regulation in 1998. In 2000, the Secretary's Advisory Committee on Genetic Testing (SACGT), the predecessor to the Secretary's Advisory Committee of Genetics, Health, and Society (SACGHS), also acknowledged this shortcoming of the law and supported CLIAC's recommendations. In 2003, HHS revised the CLIA regulations and included some of CLIAC's proposals. Nevertheless, some continued to maintain that a separate subspecialty for genetic screening should be created. But in November 2006, CMS told SACGHS that there is no need for a subspecialty for genetic testing, and that in fact CLIA-88 regulations already fully cover genetic testing. For more information see the CMS website, www.cms.hhs.gov.
In addition to the role of CMS, the Centers for Disease Control and Prevention's Environmental Health Laboratory evaluates the performance of laboratories involved in the analysis of newborn screening tests and provides technical assistance to resolve diagnostic problems. For more information see the CDC website, www.cdc.gov.
27. The Food and Drug Administration (FDA) is responsible for ensuring the safety and efficacy of medical devices. Included within this category are genetic test kits, including newborn screening test kits. Recently, the FDA has been considering the safety and efficacy of MS/MS. In fact, in 2004 the Center for Devices and Radiological Health of the FDA published detailed guidance for industry and FDA staff on the use of MS/MS. See the following for more information: Center for Devices and Radiological Health, Food and Drug Administration, “Class II Special Controls Guidance Document: Newborn Screening Test Systems for Amino Acids, Free Carnitine, and Acylcarnitines Using Tandem Mass Spectrometry,” November 24, 2004. For more information see the FDA website, www.fda.gov.
28. The Federal Trade Commission (FTC) regulates these aspects of the tests. See the FTC website, www.ftc.gov, for more information.
29. See Kay Johnson, et al., “Financing State Newborn Screening Programs: Sources and Uses of Funds,” Pediatrics 117 (2006): S270-S279; and Bradford L. Therrell, et al., “Status of Newborn Screening Programs,” S212-S252.
31. Where no fee is charged, the cost of screening is covered by a combination of state and federal revenues. If a fee is charged, it may be paid by Medicaid, SCHIP, private insurers, health providers, laboratories, hospitals, or the parents themselves. (Kay Johnson, et al., “Financing State Newborn Screening Programs: Sources and Uses of Funds,” pp. S271, S276.)
32. Bradford L. Therrell, et al., “Status of Newborn Screening Programs.”
33. See the National Newborn Screening and Genetics Resource Center's “National Newborn Screening Status Report” at http://genes-r-us.uthscsa.edu/nbsdisorders.pdf.