Enhanced interpretation of newborn screening results without analyte cutoff values (original) (raw)

NeoScreen: A Software Application for MS/MS Newborn Screening Analysis

2004

The introduction of the Tandem Mass Spectrometry (MS/MS), in neonatal screening laboratories, has opened the doors to innovative newborn screening analysis. With this technology the number of metabolic disorders, that can be detected, from dried blood-spot species, increases significantly. However, the amount of information obtained with this technique and the pressure for quick and accurate diagnostics raises serious difficulties in the daily data analysis. To face this challenge we developed a software system, NeoScreen, which simplifies and allow speeding up newborn screening diagnostics. Paper Domain:Health bioinformatics and genomics Statistical methods and tools for biological and medical data analysis

Four years of expanded newborn screening in Portugal with tandem mass spectrometry

Journal of Inherited Metabolic Disease, 2010

Introduction The Portuguese Neonatal Screening Programme (PNSP) was started in 1979 for phenylketonuria (2,590,700 newborns screened; prevalence 1:11,031) and, shortly after, for congenital hypothyroidism (2,558,455 newborns screened; prevalence 1:3,174). In 2004, expanded neonatal screening was implemented in the National Laboratory. The programme is not mandatory and has 99.8% coverage of the country (including Madeira and the Azores islands). Material and methods In the past 4 years, 316,243 neonates were screened with the use of tandem mass spectrometry (MS/MS) to test for selected amino acids and acylcarnitines. Results During this time, 132 patients were identified with 24 different inherited metabolic diseases (classic forms and variants). To date, the global frequency for all disorders integrated into the PNSP is estimated to be 1:1,380, with 1:2,396 for metabolic disorders. A total of 379 tests (0.12%) were classified as having false positive results, yielding an overall specificity of 99.9%. Despite the low frequency of several disorders, the positive predictive value of the overall MS/MS screening was found to be 26%, reflecting high diagnostic specificity of the method. Diagnostic sensitivity of extended screening for the different groups of disorders was 100%. Eight cases of maternal disorders [three glutaric aciduria type I, one carnitine transporter defect, and four 3-methylcrotonyl coenzyme A (CoA) carboxylase deficiency] were also detected through newborn screening. Conclusions Our data support the advantage of a centralised laboratory for screening an elevated number of samples and making decisions if relying on a clinical network able to provide fast treatment and a good outcome in the screened cases.

Nationwide survey of extended newborn screening by tandem mass spectrometry in Taiwan

Journal of Inherited Metabolic Disease, 2010

In Taiwan, during the period March 2000 to June 2009, 1,495,132 neonates were screened for phenylketonuria (PKU) and homocystinuria (HCU), and 1,321,123 neonates were screened for maple syrup urine disease (MSUD), methylmalonic academia (MMA), medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) deficiency, isovaleric academia (IVA), and glutaric aciduria type 1 (GA-1) using tandem mass spectrometry (MS/MS). In a pilot study, 592,717 neonates were screened for citrullinemia, 3-methylcrotonyl-CoA carboxylase deficiency (3-MCC) and other fatty acid oxidation defects in the MS/MS newborn screening. A total of 170 newborns and four mothers were confirmed to have inborn errors of metabolism. The overall incidence was approximately 1/5,882 (1/6,219 without mothers). The most common inborn errors were defects of phenylalanine metabolism [five classic PKU, 20 mild PKU, 40 mild hyperphenylalaninemia (HPA), and 13 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency]. MSUD was the second most common amino acidopathy and, significantly, most MSUD patients (10/13) belonged to the Austronesian aboriginal tribes of southern Taiwan. The most frequently detected among organic acid disorders was 3-MCC deficiency (14 newborns and four mothers). GA-1 and MMA were the second most common organic acid disorders (13 and 13 newborns, respectively). In fatty acid disorders, five carnitine transport defect (CTD), five short-chain acyl-CoA dehydrogenase deficiency (SCAD), and two medium-chain acyl-CoA dehydrogenase (MCAD) deficiency were confirmed. This is the largest case of MS/MS newborn screening in an East-Asian population to date. We hereby report the incidences and outcomes of metabolic inborn error diseases found in our nationwide MS/MS newborn screening program.

Cost-Benefit Analysis of Universal Tandem Mass Spectrometry for Newborn Screening

Pediatrics, 2002

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 qualityadjusted life year saved by MS/MS screening was 5827;intheleastfavorablescenario,thiscostwas5827; in the least favorable scenario, this cost was 5827;intheleastfavorablescenario,thiscostwas11 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. Pediatrics 2002;110:781-786; costs and cost analysis, homocystinuria, maple syrup urine disease, metabolism, inborn errors, neonatal screening, spectrum analysis, mass.