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NEJM Editorial Volume 346:1084-1085 April 4, 2002 Number 14 The Science and Politics of Screening Newborns A major accomplishment of the public health system has been the development of programs of screening newborns for inherited and congenital metabolic disorders. This effort began in response to the observation that severe mental retardation associated with phenylketonuria could be prevented by the early initiation of a diet low in phenylalanine in affected newborns.1 As a result, universal systems of care were put into place for screening and tracking newborns. When evidence supported benefits from the early detection of and intervention for other disorders, screening tests for these disorders were readily added to the existing systems, resulting in broad access and lower net costs. The medical research community, both commercial and academic, has continued to explore, at an accelerating rate, potential screening tests to be included in newborn screening programs. Determining which tests are appropriate may be a controversial issue. In the past, new tests have been included only if the disorder was an important health problem, if there was an economical screening test with a high detection rate and a low false positive rate, and if there was an effective intervention to treat the disorder and prevent associated complications.2,3,4,5 The program has expanded largely on the basis of these criteria, and there is now universal newborn screening in the United States for phenylketonuria, congenital hypothyroidism, galactosemia, and hemoglobinopathies. Approximately half the states have also added screening for biotinidase deficiency, congenital adrenal hyperplasia, and maple syrup urine disease.5 However, determining which disorders meet the criteria for screening involves both scientific and political judgments, and decisions are often based on incomplete data. The studies of screening for neuroblastoma that are reported in this issue of the Journal6,7 are examples of what is involved in the complex decision-making process that is necessary to maintain the effectiveness and credibility of screening as a public health program. These large studies were designed to evaluate prospectively whether population-based screening for neuroblastoma could reduce mortality due to this disease. Woods et al.6 assessed screening at three weeks and six months of age among 476,654 children in Quebec, Canada, and Schilling et al.7 studied screening at one year of age among 2,581,188 children in Germany. These groups concluded that although screening for catecholamines in the urine detected many cases of neuroblastoma before symptoms developed, such screening did not reduce neuroblastoma-associated mortality6,7 or the incidence of advanced-stage disease.7 This lack of benefit was attributable to the failure of screening to identify neuroblastomas in many infants who subsequently presented with the fatal progressive form of the disease and to the detection by screening of many tumors that would have regressed spontaneously, which resulted in the use of unnecessary and potentially harmful interventions. As these studies illustrate, the decision about whether or not to screen should be driven not by the availability of a laboratory screening test but by careful analysis of outcomes, including saving the lives of the screened newborns or improving their quality of life. Laboratory developments have resulted in automated high-volume, rapid-throughput equipment that can perform multiple assays. These new techniques include tandem mass spectrometry, high-pressure liquid chromatography, and the use of DNA chips. Such developments, in turn, have resulted in an increased need for information-processing technology with which to interpret complex results, monitor quality, and track outcomes. The interpretation of test results often depends on the sex or age of the patient at the time of testing or requires the assessment of combinations of multiple tests - to determine, for example, the phenylalanine:tyrosine ratio (for phenylketonuria screening) or whether there is a simultaneous elevation of leucine, isoleucine, and valine levels (in screening for maple syrup urine disease). The need for expensive technology and the rapid expansion of the group of disorders for which newborn screening is possible have created a problem for smaller states. Parents, advocates of screening, and test manufacturers are pressuring states to expand their programs to include testing for disorders of fatty-acid oxidation as well as organic acid and other amino acid disorders. These groups have called attention to substantial variation among the states in the number of disorders for which screening is performed, the quality of testing, and the comprehensiveness of follow-up and treatment of affected newborns. As a result, newborn screening in the United States is now receiving intense scrutiny. The Secretary's Advisory Committee on Genetic Testing of the Department of Health and Human Services is evaluating these programs, as are the American Academy of Pediatrics5 and the American College of Medical Genetics, with support from the Health Resources and Services Administration. Senators Christopher Dodd (D-Conn.) and Mike DeWine (R-Ohio) recently requested that the General Accounting Office review this specialized area of public health. The current interest in the screening of newborns should be welcomed by states that are struggling to maintain comprehensive, high-quality programs. Issues such as which disorders meet the criteria for mandatory screening of the population, what the accepted objectives and outcomes of screening are, and what policies and procedures must be implemented in order to meet these objectives are legitimate subjects of debate. Even in states where there is consensus on these issues, however, lack of resources has been the chief impediment to improving screening programs. Because there has been very little targeted federal support for newborn screening, these programs are state-funded and are administered by state personnel and laboratories. State allocations for maternal and child health under Title V of the Social Security Act are inadequate to meet basic needs and are not a resource for the expansion of newborn screening programs. Current constraints on funding have led some states to contract with other states in their region or with private laboratories for the actual testing. However, testing itself is only one element of the system. States must educate physicians and families about screening, ensure that there is follow-up of missed or initially positive tests, and make referrals for expedited intervention at centers that specialize in metabolic disorders. Performance standards for laboratories and other private contractors also must be specified and monitored if such arrangements are to work. To ensure the stability of newborn screening programs and to maintain acceptable standards nationally, these programs should become the joint responsibility of the federal and state governments. The addition of screening for sickle cell anemia to screening programs offers a model for successful federal-state partnership. At a consensus conference, the National Institutes of Health presented evidence from a multicenter study that early treatment with penicillin dramatically reduced the mortality associated with pneumococcal infection, a major risk for affected newborns with sickle cell disease or trait, and recommended newborn screening.8 Start-up funding from Congress enabled states to implement this additional testing rapidly. This model also suggests that states would benefit from the establishment of a federally funded national clearinghouse that would collect the scientific evidence for and against additional screening tests, including the results of studies such as those reported in this issue of the Journal.6,7 Funding for newborn screening should be provided either through Title XXVI of the Children's Health Act of 2000 or by a new targeted federal-state matching program. States should be required to maintain a basic level of newborn screening services and to document that all newborns are accurately and efficiently screened for a minimal number of disorders and that all affected newborns receive appropriate specialty care. Federal funding should be sufficient to ensure that an adequate infrastructure exists to support both testing and follow-up in each state. It is sometimes impossible in practice to meet the expectations that a screening test will have a high detection rate and a low false positive rate and that a highly effective intervention will be available. However, the effectiveness of newborn screening compares favorably with that of most decentralized clinical screening efforts, such as prenatal screening for Down's syndrome and screening of adults for colorectal and breast cancers. The U.S. Preventive Services Task Force ranked newborn metabolic screening 8th in their prioritization of 50 prevention programs.9 With a mechanism for evidence-based decision making and with sufficient federal and state support, comprehensive, high-quality screening should be available to every newborn in the United States.
George Cunningham, M.D., M.P.H. State of California Department of Health Services Berkeley, CA 94704-1011
References 1.Cunningham GC. Phenylketonuria and other inherited metabolic defects. In: Wald N, Leck I, eds. Antenatal and neonatal screening. 2nd ed. Oxford, England: Oxford University Press, 2000:353-60. 2.Wilson MMC. Jungner principles and practices of screening for disease. Public health papers. No. 34. Geneva: World Health Organization, 1968. 3.Report of a WHO scientific group: screening for inborn errors of metabolism. WHO Tech Rep Ser 1968;401:1-57. 4.Committee for the Study of Inborn Errors of Metabolism, National Research Council. Genetic screening: programs, principles, and research. Washington, D.C.: National Academy of Science, 1995. 5.Serving the family from birth to the medical home: newborn screening: a blueprint for the future -- a call for a national agenda on state newborn screening programs. Pediatrics 2000;106:389-422.[Full Text] 6.Woods WG, Gao R-N, Shuster JJ, et al. Screening of infants and mortality due to neuroblastoma. N Engl J Med 2002;346:1041-1046.[Abstract/Full Text] 7.Schilling FH, Spix C, Berthold F, et al. Neuroblastoma screening at one year of age. N Engl J Med 2002;346:1047-1053.[Abstract/Full Text] 8.Consensus conference: newborn screening for sickle cell disease and other hemoglobinopathies. JAMA 1987;258:1205-1209.[Medline] 9.Coffied AB, Maciosek MV, McGinnis JM, et al. Priorities among recommended clinical preventive services. Am J Prev Med 2001;21:1-9. |