title: Synthesis framework estimating prevalence of MCADD and sensitivity of newborn screening programme in the absence of direct evidence.
abstract: OBJECTIVE
  Several countries have included medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in their newborn screening programs. However, the sensitivity of the programs cannot be estimated directly as only individuals with a positive result undergo a definitive diagnostic test. We propose a framework to overcome this limitation and estimate the prevalence of disease, sensitivity of screening, and its yield relative to no screening.
  
  
  METHODS
  A Bayesian model simultaneously combined available prevalence data on the most common mutation of MCADD (c.985A>G) in screened and nonscreened populations using the relationship between true and apparent prevalence of disease. Data originated from screening pilots in England, disease surveillance studies, and published literature. Model validity and consistency were formally checked.
  
  
  RESULTS
  True prevalence of c.985A>G homozygotes in England was 6.2 per 100,000 individuals, and the sensitivity of the screening program was 94% (95% confidence interval [CI]: 74, 100%) compared with a detection rate in nonscreened areas of 48% (95% CI: 30, 68%) by age of 5 years. Hence, the screening program detected 47% (95% CI: 30, 60%) additional cases compared with no screening.
  
  
  CONCLUSIONS
  The sensitivity of the screening program in England was high and our estimation approach could be adapted to inform other jurisdictions, rare diseases, and newborn screening programs.
authors.affiliation: Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK. Electronic address: jose.leal@dph.ox.ac.uk.
authors.forename: Jose
authors.initials: J
authors.lastname: Leal
authors.affiliation: Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wordsworth
authors.affiliation: Medical Research Council Centre of Epidemiology for Child Health, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
authors.forename: Juliet
authors.initials: J
authors.lastname: Oerton
authors.affiliation: Medical Research Council Centre of Epidemiology for Child Health, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
authors.forename: Javaria M
authors.initials: JM
authors.lastname: Khalid
authors.affiliation: Medical Research Council Centre of Epidemiology for Child Health, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
authors.forename: Carol
authors.initials: C
authors.lastname: Dezateux
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D000293:Adolescent; D001499:Bayes Theorem; D002648:Child; D002675:Child, Preschool; D004739:England / Q000453:epidemiology; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000453:epidemiology* / Q000235:genetics*; D015997:Neonatal Screening; D015995:Prevalence; D015397:Program Evaluation; D012680:Sensitivity and Specificity
chemical_list: D042964:Acyl-CoA Dehydrogenase
keywords: Inborn errors of metabolism; MCADD; Medium chain acyl-CoA dehydrogenase deficiency; Screening; Sensitivity; Tandem mass spectrometry