PEDIATRICS Vol. 110 No. 4 October 2002, pp. 781-786
Cost-Benefit Analysis of Universal Tandem Mass Spectrometry for Newborn Screening
* Department of Genetics, Kaiser Permanente Medical Center, Oakland, California
Division of Research, Kaiser Permanente Medical Care Program, Oakland, California
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
|---|
Objective. To estimate potential costs and benefits of routinely using tandem mass spectrometry (MS/MS) to screen newborns for inborn errors of metabolism.
Method. Analysis of costs and benefits resulting from use of MS/MS in screening of 32 000 newborn infants using data from the Kaiser Permanente Medical Care Program of Northern California plus other published data.
Setting. A large health maintenance organization.
Results. In the base scenario, the cost per quality-adjusted life year saved by MS/MS screening was $5827; in the least favorable scenario, this cost was $11 419, and in the most favorable scenario, $736.
Conclusion. Costs per quality-adjusted life year saved by MS/MS screening for inborn errors of metabolism compare favorably with other mass screening programs, including those for breast and prostate cancer.
Key Words: costs and cost analysis • homocystinuria • maple syrup urine disease • metabolism • inborn errors • neonatal screening, • spectrum analysis • mass
Abbreviations: MS/MS, tandem mass spectrometry • IEM, inborn errors of metabolism • NBS, newborn screening • KP, Kaiser Permanente • PKU, phenylketonuria • MSUD, maple syrup urine disease • MMA, methylmalonic acidemia • PPA, propionic acidemia • MCAD, medium-chain acyl-CoA dehydrogenase deficiency • QALY, quality-adjusted years of life
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
|---|
Tandem mass spectrometry (MS/MS) is being used increasingly in early diagnosis of inborn errors of metabolism (IEM) in the hope of avoiding the severe developmental delay, acute illness, and death that may result from these diseases.1–13 Although >30 types of IEM can be diagnosed with the aid of MS/MS, its universal, routine use is controversial because of the rarity of these disorders, questions of treatability and outcome, and concern about high costs.11,14–20 With rapid expansion of universal newborn MS/MS screening in an increasing number of states,1,3–5 the economic impact of this laboratory technology on newborn screening (NBS) becomes relevant. Here, we estimate the potential impact on costs and benefits of MS/MS in NBS in a large health maintenance organization.
|
METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
|---|
Sources of Cost Data
For cost analysis, we used NBS cost data from Kaiser Permanente (KP) of Northern California, a health maintenance organization region that serves >3 million members and at which 32 000 infants are delivered each year; reference cost data from outside sources; and estimated costs incurred in early versus late diagnosis of IEM. In line with California policy, NBS tests are performed in the regional KP laboratory using standardized equipment provided by the state. The current California NBS program tests for congenital hypothyroidism, phenylketonuria (PKU), galactosemia and hemoglobinopathies. Although PKU can be diagnosed by MS/MS along with many inborn metabolic disorders, the other conditions (congenital hypothyroidism, galactosemia, hemoglobinopathies) can not. To estimate the costs of early and late treatment as well as rates of false-positive test results, we used previously published data4–7,14,18,20 in addition to KP internal data.
Internal cost data were obtained from the KP Cost Management Information System, an automated system, which integrates KP’s Northern California Regional Medical Utilization database and the KP General Accounting Ledger and itemizes fully allocated costs by department, by medical center, by patient, and by procedure. Cost Management Information System also uses data from a separate referral database of medical utilization at non-KP facilities.
In addition, cost estimates for treatment and follow-up were based on information from the KP Regional Metabolic Clinic, which currently manages metabolic disorders in >200 children, including 7 children with maple syrup urine disease (MSUD), 8 with methylmalonic acidemia (MMA) or propionic acidemia (PPA), and 96 with PKU. In addition to these internal data, our analysis included amounts of required follow-up care estimated by our 4 metabolic geneticists on the basis of their experience.
Lifetime Discounted Treatment Cost
"Lifetime discounted treatment cost" was considered in the calculations because in screening programs money is spent today for future benefits. In general, gains of all types, including health gains, are preferred to occur earlier rather than later, and a discount factor is applied to account for this time preference. We used a 3% lifetime discounted cost, a commonly used figure. Failure to discount could encourage policymakers to delay implementing health programs indefinitely.21,22
Estimated Disease Incidence and Rates of False-Positive Test Results
Estimated treatment costs included 7 general categories of IEM, for which the following incidence rates were assumed3,4,18,19: MSUD, 1:20 000; medium-chain acyl-CoA dehydrogenase deficiency (MCAD) and other disorders of fatty acid oxidation, 1:10 000; glutaric aciduria, type I, 1:20 000; MMA/PPA (included here as examples of organic acid disorders), 1:50 000; urea cycle disorders, 1:50 000; homocystinurea, 1:200 000; PKU, 1:15 000.
For all these disorders except PKU, we assumed a false-positive:true-positive ratio of 25:1. This assumption was made on the basis of our experience and published reports of actual and estimated false-positive rates ranging from 5:1 to 50:1.3,4,18,19 With added experience, the false-positive-to-true-positive ratio may decrease, and the decrease in false-positive tests would increase the cost benefit of the test. For PKU, we assumed a false-positive:true-positive ratio similar to the 8:1 ratio currently achieved in California with the fluorometric method; the 600 000 NBS tests conducted at KP from 1978 through 2000 showed a false-positive:true-positive ratio of 14:1 for PKU and 8:1 for congenital hypothyroidism.
To estimate number of quality-adjusted life years (QALY) saved by prevention of neurologic deficit, we used published data from studies of other disorders that cause neurologic defects.23–26 The subject of these studies were adults; no comparable information is available in children. Costs of MS/MS analysis were based on values obtained from US States (eg, North Carolina, Wisconsin, and Pennsylvania) currently using MS/MS3,4,12 and on charges obtained from commercial laboratories. Costs for false-positive test results were estimated using internal KP data for existing NBS programs. Sensitivity analysis was used to estimate effects of changes in base assumptions. Various ranges of test costs, treatment costs, rates and costs of false-positive test results, mortality rates, and adjustments for QALY were used. In addition to our base set of assumptions, we created 2 alternative sets of assumptions: 1 set was based on a scenario least favorable to MS/MS screening, and another set was based on a scenario most favorable to MS/MS. The analysis did not include cost of special education programs or cost of labor value gained by preventing neurologic deficit.
Estimated Base Costs Incurred and Saved as a Result of Early Diagnosis
The base laboratory cost for MS/MS was estimated at $15 per test and included the costs of prompt specimen transportation, processing, and interpretation of results. The State of California currently mandates that blood samples taken for NBS be drawn when the newborn is discharged from the hospital but no sooner than age 12 hours and no later than age 6 days (most newborns are discharged from the hospital at age 24–72 hours). Because presymptomatic treatment is particularly important in most IEM, eg, MSUD or urea cycle defects,11,27 quick diagnosis and management are necessary and require early collection of specimens (ie, before age 48 hours), rapid turnaround time, and continuous availability of metabolic specialists and emergency services. In addition, laboratories should perform MS/MS 7 days per week and also have a replacement machine readily available.
Infants with MSUD and other IEM may become symptomatic within the first week of life and may require hospitalization,11 usually in neonatal intensive care units at a cost which often exceeds $35 000; infants whose metabolic disease is detected presymptomatically by MS/MS require shorter, less intensive hospital stays. For analysis of the base scenario, we assumed an initial treatment cost savings of $25 000 for presymptomatic diagnosis versus diagnosis made after symptoms manifested.
Costs of treatment received during the first 5 years of life were estimated on the basis of experience at KP, where 3 major cost factors apply: 1) special tests are done repeatedly for each patient; 2) patients must be diagnosed and treated in costly multispecialty clinics, such as the KP Regional Metabolic Clinic; and 3) disease-specific formulas usually required during treatment cost about $10 000 annually. Moreover, particularly during the first 5 years of life, additional care is needed for children with IEM detected after symptoms manifest. This additional care is needed because these children have greater global developmental delay as well as greater susceptibility to infection. These factors increase outpatient costs as well as the likelihood of both hospital admission and care in the intensive care unit. We assumed an annual hospital admission rate of 25% for patients aged 
5 years with IEM diagnosed late; we assumed an annual admission rate of 7.5% for patients with IEM diagnosed before symptoms manifested.
For analysis of the base scenario, we estimated long-term treatment costs by assuming that among patients aged >5 years, the annual hospital admission rate was 9% if IEM were diagnosed late and was 3% if IEM were detected early.
In addition, we assumed a 20-year difference in life expectancy between affected patients diagnosed late (life expectancy of 45 years) and those diagnosed early by screening (life expectancy of 65 years). With regard to sensitivity testing of IEM detection among affected patients diagnosed early versus late, we assumed a 15-year difference in life expectancy between groups of patients diagnosed in the least favorable scenario (ie, least sensitive IEM detection) and a 25-year difference in life expectancy between groups of patients diagnosed in the most favorable scenario.
Our analysis included a small cost offset for PKU, because use of total mass spectrometry will eliminate the current need for PKU laboratory testing.
Estimated Costs of False-Positive Test Results
Because of the immediate response required to treat IEM diagnosed by MS/MS, false-positive test results are costly. The diagnosis necessitates immediate response by a genetics nurse-coordinator ($100), a visit to an urgent care clinic ($110), several laboratory tests (costing as much as $600 total), and, in some cases, consultation with a geneticist ($200). Some false-positive test results engender a visit to the emergency department ($200), admission to the hospital for an overnight stay ($2000), or both. On the basis of these estimated costs, each disorder was assigned a cost of $1000 for every false-positive test result. (Costs associated with various disorders differ slightly from one another because of the different laboratory tests required and because of different response times, but these cost differences are relatively small.) Because MCAD usually requires no immediate intervention, the cost of each false-positive test result was set at $200 to cover costs of conducting repeat laboratory tests and tracking results of these tests.
Quantifying Changes in Morbidity and Quality of Life
The effect of early, presymptomatic diagnosis of most IEM will be primarily on quality of life rather than mortality. To account for this effect, we adjusted mortality for quality of life. Estimates of utility level of patients with serious neurologic defects range from 0.15 to 0.30 (normal value of 1). Early detection of IEM was estimated to result in the addition of between 0.70 and 0.80 QALY. MCAD was assumed to rarely cause developmental effects and just the possibility of sudden infant death syndrome.3–5,8–11,27 Although cases of undiagnosed MCAD are known to cause severe hypoglycemia, no health plan members have been diagnosed with MCAD in the KP Northern California system. (The rationale for the MCAD assumption is described in the "Discussion" section.)
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
|---|
Results are presented in Tables 1 through 5. Costs are listed both per screened infant and for a cohort of 100 000 births. Costs of false-positive test results range from $1.21 to $12.25 per infant screened, depending on rate of false-positive test results (Table 5). Early diagnosis resulted in lifetime treatment cost savings ranging from $4.86 to $5.98 per test performed (Table 5). Most savings in treatment costs in early diagnosed cases were realized within the first 5 years of life, because of decreased hospitalization costs (Table 5). The biggest cost factor was initial laboratory cost, estimated at $15 in the base scenario with a range of $7 to $20 per test. Because of the reduced mortality rates and improved QALY resulting from early diagnosis, each patient screened gained a mean of 0.0026 QALY (Table 5). The cost per QALY was $5827 in the base scenario.
|
|
|
|
|
In the unfavorable scenario—ie, higher laboratory costs, more false-positive test results, and smaller effects on rates of mortality and morbidity—cost per QALY was $11 419; in the favorable scenario, cost per quality-adjusted year of life was $736. In the unfavorable scenario, cost of false-positive test results was even more important: Mean per-test cost of false-positive test results was $12.25. Assumptions regarding the value of early detection in relation to QALY were also important.
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
|---|
Our analysis showed that the cost of MS/MS per QALY compares favorably with other screening methods as well as with other types of treatment. Prostate cancer screening has been estimated to cost between $8400 and $23 100 per QALY, whereas breast cancer screening has been estimated to cost $5815 among patients of all ages.28 Breast cancer screening for women under 50 years old has been estimated to cost $232 000 per QALY.28 Semiannual screening for retinopathy in high-risk patients with type 2 diabetes has an estimated cost of $49 760 per QALY.29 Beta-interferon treatment for hepatitis C has been estimated to cost $7500 per QALY.30 Equipping commercial aircraft with onboard automatic external defibrillators to improve passengers’ rate of survival after cardiac arrest costs an estimated $50 000 per QALY.31
Medical cost savings resulting from early diagnosis occurs primarily in the first 5 years of life as a result of decreased ICU and hospital costs. Even patients with IEM detected early will require expensive formula and dietary supplements as well as increased outpatient care throughout life (Table 4). For patients aged >5 years, differential costs are less because rates of hospitalization in both groups decrease. Thus, the reduced hospital costs early in life are slightly offset by cost incurred by expected increased longevity. Because early detection enables patients to live longer, these long-term follow-up costs can rise when screening is introduced.
There is evidence that diagnosis of MSUD between the third and seventh days of life, followed by effective treatment, reverses intoxication within 24 to 48 hours and decreases the risk of brain damage.32 If MSUD is subsequently well managed, these infants will grow and develop normally. If the diagnosis is not made until the infant becomes symptomatic, often at 5 to 21 days of age, prolonged hospitalizations and intensive care are required, and there is increased risk of poor developmental outcomes.33–36
MCAD requires special consideration as the most common of the IEM: Its estimated prevalence is 1:10 000 to 1:20 000.1,4–11 Evidence indicates that most people born with MCAD do not have serious sequelae.8–10 A study of 20 patients with MCAD in New South Wales8 included 5 patients (25%) who died at age 3 days to 30 months and 2 patients (10%) who had serious, life-threatening episodes after diagnosis. The 15 survivors included 1 (5%) who had severe neurologic disabilities and 4 (20%), aged between 9 and 17 years, who had mild intellectual handicap. However, the patients in that series8 represent only 22% of all persons born with MCAD; thus, assuming a 1:20 000 prevalence of MCAD, death rate is 5%; rate of severe handicap, 1%; and rate of mild handicap, 4%. Data from recent US screening programs suggest MCAD prevalence of 1:10 000 1,4–7,11; combining this incidence with the data of Wilcken et al8 yields a death rate of 2.5%, 0.5% rate of severe handicap, and 2% rate of mild handicap-a 5% rate of adverse outcome among infants and children born with MCAD. Of 41 MCAD cases analyzed by Wilson et al,9 nearly half the patients had been admitted to the hospital because of symptoms suggesting MCAD, and severe encephalopathy later developed in 2 (5%), but no deaths or "appreciable morbidity"9 occurred. A retrospective study10 reported that 19% of 120 MCAD patients died and that "unexpected morbidity"10 occurred in the survivors. But, as in the other 2 studies,8,9 affected patients came to the authors’ attention after treatment and not prospectively through NBS. Our experience at KP confirms the likelihood that most patients with MCAD do not have symptoms of the disease and therefore would not be identified in the absence of a screening program. In our large metabolic clinics, we have treated >200 patients with IEM, including 97 with PKU-and MCAD is at least as prevalent as PKU in the general population. Yet we currently have no patients with MCAD, although we are treating children affected with MSUD, MMA/PPA, and other IEM that are detected much less frequently than MCAD in screening programs.1,4–11 Medical management of MCAD is also less complex and costly than for other IEM; hallmarks of treatment for MCAD include frequent feeding (to avoid hypoglycemia), adherence to a low-fat diet, and administration of carnitine. We believe that the infrequency of symptoms and sequelae and the low cost of treatment justify our assumption that the economic impact of MCAD is smaller than for more uncommon IEM with more severe sequelae. If subsequent prospective studies of total mass spectrometry screening programs show that rates of death and morbidity are higher than our conservative estimates of 3% to 7%, such findings would substantially decrease the costs of QALY and more strongly favor MS/MS screening.
The rate of false-positive test results is an important cost factor in using MS/MS for NBS. In some current screening programs, the ratio of false-positive:true-positive test results has been higher than 50:1.4 We assumed a smaller ratio, 25:1, for analysis of the base scenario. A low rate of false-positive test results can be achieved only if 3 conditions are met: 1) MS/MS is used to screen for prespecified abnormalities only; 2) MS/MS screening is not used to evaluate all substances ascertainable by this highly sensitive technology; and 3) positive test results are determined according to a reasonable, preset cutoff point. For those MS/MS programs not limiting their scope of diagnosis, false-positive rates and costs will probably be appreciably higher.
Other pediatric screening programs19,37–42 have shown that a false-positive test result can have a long-term, detrimental effect on the parents, may influence the way parents view their offspring, and may lead to an overprotective attitude toward the child. Despite assurances to the contrary and despite normal results of follow-up tests, some parents feel that something must have been wrong with the child for the test to have been initially positive. Thus, maintaining a low rate of false-positive test results is important from a clinical and sociologic viewpoint as well as from an economic standpoint, and this importance should be considered in a decision to implement screening. Although screening programs using MS/MS may seem to yield higher rates of false-positive test results than do many other screening programs, data reported by some large MS/MS screening studies have not specified rates of false-positive test results.1,3,5,7 Failing to consider the costs of false-positive tests ignores an important cost factor and biases these programs in favor of screening.
In addition to increasing laboratory costs and causing parental anxiety, false-positive test results can generate a cascade of costly clinical events, including emergency department visits, hospital admissions, additional definitive laboratory studies, and use of on-call medical personnel (including metabolic specialists). Cost analyses of screening programs are often limited to laboratory expenses and some treatment costs; the analyses generally ignore other costs, ie, costs of confirming the diagnosis, tracking test results, counseling, clinical visits, and treatment follow-up. Instituting a new screening procedure is best accomplished not just by adding advanced laboratory technology but by introducing a total tracking and follow-up program. Failure to realize this fact may result in grossly underestimated costs. To emphasize the complexity and importance of a total screening program, we have developed an acronym for the multiple steps involved. We call these multiple steps the "11 Ts" of screening: 1) technology (equipment), 2) training (personnel), 3) taking (specimen collection), 4) transportation of specimens, 5) testing, 6) telling (reporting test results), 7) tracking (confirming results, false-positive), 8) teaching (counseling subjects and providers), 9) treating, 10) tracking (long-term follow-up, outcomes), 11) totaling (sum of all costs). Others have recognized some of these limitations.43
Because severe clinical manifestations of many IEM (eg, MSUD, urea cycle disorders) may occur in the immediate neonatal period, a highly coordinated screening program with fast laboratory turnaround time and rapid clinical intervention by highly trained professionals is required. A sophisticated tracking program is necessary for follow-up and to guarantee patients’ compliance with prescribed treatment regimens. These rapid-response screening and tracking programs are expensive but are rarely included in cost analysis studies. Implementing such a highly coordinated system may be difficult under certain circumstances, such as in rural areas and in programs without close laboratory or clinical cooperation. Most patients with IEM incur high dietary costs throughout life, beginning with formula required in infancy and early childhood and continuing with specially formulated foods required later in life. In recognition of these dietary requirements, the State of California—which previously had mandated that medical insurance for patients with IEM cover only the cost of formula—recently added the requirement that the cost of special foods be covered in older persons with IEM.44
Study Limitations
Our search of the biomedical literature on MS/MS screening did not show reported rates of false-positive test results similar to the rates used in our analysis. Indeed, some evidence4 suggests that rates of false-positive test results obtained by using MS/MS will be much higher than the 14:1 ratio we found for NBS tests conducted at KP; however, data reported in most large MS/MS studies do not include rates of false-positive test results.1,3,5,7 Ratio of false-positive:true-positive test results in 1 US state fluctuated between 8:1, 41:1, and 9:1 at different times during the screening program.4
Because the IEM we considered are so rare and because early diagnosis and longitudinal studies of patients with these conditions are even rarer, several of our assumptions relating to cost, morbidity rates, and mortality rates were based either on a small number of published observations16–20,27 or on projections made by KP metabolic geneticists from their own clinical experience. Moreover, until the past 2 decades, IEM often proved fatal during infancy or early childhood; therefore, long-term survival rates among patients with these disorders are not yet known.16,17
|
CONCLUSION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
|---|
Whether detected presymptomatically (ie, by screening) or after symptoms manifest, IEM in infants and children is expensive to manage. Our finding that the cost of MS/MS screening per quality-adjusted year of life compares favorably with costs of other accepted screening procedures supports a policy of encouraging MS/MS screening. However, when a program of NBS using MS/MS is financed, the calculations should consider total expenses, including costs not only of equipment and analysis but also costs of training, personnel, tracking test results, counseling parents, supplying special diets and specialty care, and clinical follow-up.
|
ACKNOWLEDGMENTS |
|---|
The Kaiser Permanente Direct Community Benefit Investment Program provided research support. The Medical Editing Department of Kaiser Foundation Hospitals, Inc, provided editorial assistance.
|
FOOTNOTES |
|---|
Received for publication Jan 25, 2002; Accepted Jun 19, 2002.
Reprint requests to (E.J.S.) Department of Genetics, Kaiser Permanente Medical Center, 280 W MacArthur Blvd, Oakland, CA 94611-5693. E-mail: edgar.schoen{at}kp.org
This work was presented at the annual meeting of the American Pediatric Society, Baltimore, MD, April 28-May 1, 2001.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
|---|
- Naylor EW, Chace DH. Automated tandem mass spectrometry for mass newborn screening for disorders in fatty acid, organic acid, and amino acid metabolism. J Child Neurol.1999; 14(suppl 1) :S4 –S8
- Simonsen H, Jensen UG. Technical aspects of neonatal screening using tandem mass spectrometry. Report from the 4th meeting of the International Society for Neonatal Screening. Acta Paediatr Suppl.1999; 432 :52 –54
- Ciske JB, Hoffman G, Hanson K, et al. Newborn screening in Wisconsin: program overview and test addition. WMJ.2000; 99 :38 –42
- Muenzer J, Frazier DM, McCandless SE, et al. Incidence and follow-up evaluation of metabolic disorders detected by newborn screening in North Carolina using tandem mass spectrometry. MMWR Morb Mortal Wkly Rep.2001; 50(RR03) :23 –34. Synopses of selected papers presented at the Tandem Mass Spectrometry for Metabolic Disease Screening Among Newborns Workshop, San Antonio, Texas, June 2000. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5003a2.htm. Accessed May 30, 2002
- Zytkovicz TH, Johnson D, Rojas D, et al. Testing newborn specimens by tandem mass spectrometry: the first 16 months’ experience in the New England Program. MMWR Morb Mortal Wkly Rep.2001; 50(RR03) :23 –34. Synopses of selected papers presented at the Tandem Mass Spectrometry for Metabolic Disease Screening Among Newborns Workshop, San Antonio, Texas, June 2000. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5003a2.htm. Accessed May 30, 2002
- Wiley V, Carpenter K, Wilcken B. Newborn screening with tandem mass spectrometry: 12 months’ experience in NSW Australia. Acta Paediatr Suppl.1999; 88 :48 –51[Medline]
- Wilcken B, Wiley V. Tandem Mass Spectrometry in the New South Wales Newborn Screening Program. MMWR Morb Mortal Wkly Rep.2001; 50(RR03) :23 –34. Synopses of selected papers presented at the Tandem Mass Spectrometry for Metabolic Disease Screening Among Newborns Workshop, San Antonio, Texas, June 2000. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5003a2.htm. Accessed May 30, 2002
- Wilcken B, Hammond J, Silink M. Morbidity and mortality in medium chain acyl coenzyme A dehydrogenase deficiency.
Arch Dis Child.1994; 70
:410
–412
[Abstract/Free Full Text] - Wilson CJ, Champion MP, Collins JE, et al. Outcome of medium chain acyl-CoA dehydrogenase deficiency after diagnosis.
Arch Dis Child.1999; 80
:459
–462
[Abstract/Free Full Text] - Iafolla AK, Thompson RJ Jr, Roe CR. Medium-chain acyl-coenzyme A dehydrogenase deficiency: clinical course in 120 affected children. J Pediatr.1994; 124 :409 –415[CrossRef][Web of Science][Medline]
- Hannon WH, Grosse SD. Using tandem mass spectrometry for metabolic disease screening among newborns. MMWR Morb Moral Wkly Rep.2001; 50(RR03) :1 –22. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5003a1.htm. Accessed May 30, 2002
- Chace DH, DiPerna JC, Naylor EW. Laboratory integration and utilization of tandem mass spectrometry in neonatal screening: a model for clinical mass spectrometry in the next millennium. Acta Paediatr Suppl.1999; 88 :45 –47[CrossRef][Medline]
- Charrow J, Goodman SI, McCabe ERG, et al. ACMG/ASHG statement. Tandem mass spectrometry in newborn screening. Genet Med.2000; 2 :267 –269[Medline]
- Pollitt RJ, Green A, McCabe CJ, et al. Neonatal screening for inborn errors of metabolism: cost, yield and outcome. Health Technol Assess.1997; 1 :1 –202
- Cederbaum S, Vilain E. Newborn screening for inborn errors of metabolism is going to expand: are we ready? J Pediatr.1999; 134 :666 –667[CrossRef][Web of Science][Medline]
- Andersson HC, Marble M, Shapira E. Long-term outcome in treated combined methylmalonic acidemia and homocystinemia. Genet Med.1999; 1 :146 –150[Web of Science][Medline]
- Sniderman LC, Lambert M, Giguère R, et al. Outcome of individuals with low-moderate methylmalonic aciduria detected through a neonatal screening program. J Pediatr.1999; 134 :675 –680[CrossRef][Web of Science][Medline]
- Pollitt RJ. Tandem mass spectrometry screening: proving effectiveness. Acta Paediatr Suppl.1999; 88 :40 –44[Medline]
- Kwon C, Farrell PM. The magnitude and challenge of false-positive newborn screening test results.
Arch Pediatr Adolesc Med.2000; 154
:714
–718
[Abstract/Free Full Text] - Green A, Pollitt RJ. Population newborn screening for inherited metabolic disease: current UK perspectives. J Inherit Metab Dis.1999; 22 :572 –579[CrossRef][Web of Science][Medline]
- Starrett DA. Foundations of Public Economics. New York, NY: Cambridge University Press; 1988:191–193
- Lipscomb J, Weinstein MC, Torrance GW. Time preference. In: Gold ME, Siegel JE, Russell LB, et al, eds. Cost-Effectiveness in Health and Medicine. New York, NY: Oxford University Press; 1996:216–234
- Johnston SC, Gress DR, Kahn JG. Which unruptured cerebral aneurysms should be treated? A cost-utility analysis. Stroke.1999; 30 :1984
- Kallmes DF, Kallmes MH. Cost-effectiveness of angiography performed during surgery for ruptured intracranial aneurysms. AJNR Am J Neuroradiol.1997; 18 :1453 –1462[Abstract]
- King JT Jr, Sperling MR, Justice AC, et al. A cost-effectiveness analysis of anterior temporal lobectomy for intractable temporal lobe epilepsy. J Neurosurg.1997; 87 :20 –28[CrossRef][Web of Science][Medline]
- Langfitt JT. Cost-effectiveness of anterotemporal lobectomy in medically intractable complex partial epilepsy. Epilepsia.1997; 38 :154 –163[CrossRef][Web of Science][Medline]
- Pollitt RJ, Leonard JV. Prospective surveillance study of medium chain acyl-CoA dehydrogenase deficiency in the UK.
Arch Dis Child.1998; 79
:116
–119
[Abstract/Free Full Text] - Thompson IM, Optenberg SA. An overview cost-utility analysis of prostate cancer screening. Oncology.1995; 9 :141 –145[Medline]
- Vijan S, Hofer TP, Hayward RA. Cost-utility analysis of screening intervals for diabetic retinopathy in patients with type 2 diabetes mellitus.
JAMA.2000; 283
:889
–896
[Abstract/Free Full Text] - Younossi ZM, Singer ME, McHutchison JG, et al. Cost effectiveness of interferon alpha2b combined with ribavirin for the treatment of chronic hepatitis C. Hepatology.1999; 30 :1318 –1324[CrossRef][Web of Science][Medline]
- Groeneveld PW, Kwong JL, Liu Y, et al. Cost-effectiveness of automated external defibrillators on airlines.
JAMA.2001; 286
:1482
–1489
[Abstract/Free Full Text] - Morton DH, Strauss KA, Robinson DL, et al. Diagnosis and treatment of maple syrup disease: a study of 36 patients.
Pediatrics.2002; 109
:999
–1008
[Abstract/Free Full Text] - Baric I, Zschocke J, Christensen E, et al. Diagnosis and management of glutaric aciduria type I. J Inherit Metab Dis.1998; 21 :326 –340[CrossRef][Web of Science][Medline]
- Morton DH. Through my window—remarks at the 125th year celebration of Children’s Hospital of Boston.
Pediatrics.1994; 94
:785
–791
[Abstract/Free Full Text] - Yoshino M, Aoki K, Akeda H, et al. Management of acute metabolic decompensation in maple syrup urine disease: a multi-center study. Pediatr Int.1999; 41 :132 –137[CrossRef][Web of Science][Medline]
- Tada K, Tateda H, Arashima S, et al. Follow-up study of a nation-wide neonatal metabolic screening program in Japan. A collaborative study group of neonatal screening for inborn errors of metabolism in Japan. Eur J Pediatr.1984; 142 :204 –207[CrossRef][Web of Science][Medline]
- Bodegard G, Fyro K, Larsson A. Psychological reactions in 102 families with a newborn who has a falsely positive screening test for congenital hypothyroidism. Acta Paediatr Scand Suppl.1983; 304 :1 –21[Medline]
- Cayler GG, Lynn DB, Stein EM. Effect of cardiac "nondisease" on intellectual and perceptual motor development.
Br Heart J.1973; 35
:543
–547
[Free Full Text] - Bergman AB. The menace of mass screening.
Am J Public Health.1977; 67
:601
–602
[Free Full Text] - Clayton EW. Issues in state newborn screening programs.
Pediatrics.1992; 90
:641
–646
[Abstract/Free Full Text] - Fyro K, Bodegard G. Four-year follow-up of psychological reactions to false positive screening tests for congenital hypothyroidism. Acta Paediatr Scand.1987; 76 :107 –114[Web of Science][Medline]
- Hall S, Bobrow M, Marteau TM. Psychological consequences for patents of false negative results on prenatal screening for Down’s syndrome: retrospective interview study.
BMJ.2000; 320
:407
–412
[Abstract/Free Full Text] - Matorn D. Tandem mass spectrometry in newborn screening. Endocrinologist.2002; 12 :50 –57[Web of Science]
- California Insurance Code. Section 10123.89. Available at:http://www.leginfo.ca.gov/calaw.html. Accessed November 29, 2001
PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Norman, M. Haas, M. Chaplin, P. Joy, and B. Wilcken Economic Evaluation of Tandem Mass Spectrometry Newborn Screening in Australia Pediatrics, February 1, 2009; 123(2): 451 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Neumann, P. D. Jacobson, and J. A. Palmer Measuring the Value of Public Health Systems: The Disconnect Between Health Economists and Public Health Practitioners Am J Public Health, December 1, 2008; 98(12): 2173 - 2180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Bishop Hubbard Policy Issues Related to Expanded Newborn Screening: A Review of Three Genetic/Metabolic Disorders Policy Politics Nursing Practice, August 1, 2007; 8(3): 201 - 209. [Abstract] [PDF]
|
|
|
|
|
|
W. B. Hanley False-positive Results in Expanded Newborn Screening Pediatrics, February 1, 2007; 119(2): 414 - 415. [Full Text] [PDF]
|
|
|
|
|
|
C. I. Kaye and Committee on Genetics Introduction to the Newborn Screening Fact Sheets Pediatrics, September 1, 2006; 118(3): 1304 - 1312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Johnson, M. A. Lloyd-Puryear, M. Y. Mann, L. R. Ramos, and B. L. Therrell Financing State Newborn Screening Programs: Sources and Uses of Funds Pediatrics, May 1, 2006; 117(5/S1): S270 - S279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Botkin Research for Newborn Screening: Developing a National Framework Pediatrics, October 1, 2005; 116(4): 862 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Griebsch, J. Coast, and J. Brown Quality-Adjusted Life-Years Lack Quality in Pediatric Care: A Critical Review of Published Cost-Utility Studies in Child Health Pediatrics, May 1, 2005; 115(5): e600 - e614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Holtzman Management of Hyperbilirubinemia: Quality of Evidence and Cost Pediatrics, October 1, 2004; 114(4): 1086 - 1088. [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Waisbren, S. Albers, S. Amato, M. Ampola, T. G. Brewster, L. Demmer, R. B. Eaton, R. Greenstein, M. Korson, C. Larson, et al. Effect of Expanded Newborn Screening for Biochemical Genetic Disorders on Child Outcomes and Parental Stress JAMA, November 19, 2003; 290(19): 2564 - 2572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Holtzman Expanding Newborn Screening: How Good Is the Evidence? JAMA, November 19, 2003; 290(19): 2606 - 2608. [Full Text] [PDF]
|
|
|
|
|
|
L. N. Venditti, C. P. Venditti, G. T. Berry, P. B. Kaplan, E. M. Kaye, H. Glick, and C. A. Stanley Newborn Screening by Tandem Mass Spectrometry for Medium-Chain Acyl-CoA Dehydrogenase Deficiency: A Cost-Effectiveness Analysis Pediatrics, November 1, 2003; 112(5): 1005 - 1015. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
