title: Expanded newborn screening: outcome in screened and unscreened patients at age 6 years.
abstract: OBJECTIVE
  Tandem mass spectrometry is widely applied to routine newborn screening but there are no long-term studies of outcome. We studied the clinical outcome at six years of age in Australia.
  
  
  METHODS
  In a cohort study, we analyzed the outcome at 6 years for patients detected by screening or by clinical diagnosis among >2 million infants born from 1994 to 1998 (1,017,800, all unscreened) and 1998 to 2002 (461,500 screened, 533,400 unscreened) recording intellectual and physical condition, school placement, other medical problems, growth, treatment, diet, and hospital admissions. Results were analyzed separately for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and other disorders, and grouped patients as those who presented clinically or died in the first 5 days of life; patients presented later or diagnosed by screening, and those with substantially benign disorders.
  
  
  RESULTS
  Inborn errors, excluding phenylketonuria, were diagnosed in 116 of 1,551,200 unscreened infants (7.5/100,000 births) and 70 of 461,500 screened infants (15.2/100,000 births). Excluding MCADD, 21 unscreened patients with metabolic disorders diagnosed after 5 days of life died or had a significant intellectual or physical handicap (1.35/100,000 population) compared with 2 of the screened cohort (0.43/100,000; odds ratio: 3.1 [95% CI: 0.73-13.32]). Considering the likely morbidity or mortality among the expected number of never-diagnosed unscreened patients, there would be a significant difference. Growth distribution was normal in all cohorts.
  
  
  CONCLUSIONS
  Screening by tandem mass spectrometry provides a better outcome for patients at 6 years of age, with fewer deaths and fewer clinically significant disabilities.
authors.affiliation: Department of Biochemical Genetics, Children's Hospital at Westmead, Sydney, Australia. bridgetw@chw.edu.au
authors.forename: Bridget
authors.initials: B
authors.lastname: Wilcken
authors.forename: Marion
authors.initials: M
authors.lastname: Haas
authors.forename: Pamela
authors.initials: P
authors.lastname: Joy
authors.forename: Veronica
authors.initials: V
authors.lastname: Wiley
authors.forename: Francis
authors.initials: F
authors.lastname: Bowling
authors.forename: Kevin
authors.initials: K
authors.lastname: Carpenter
authors.forename: John
authors.initials: J
authors.lastname: Christodoulou
authors.forename: David
authors.initials: D
authors.lastname: Cowley
authors.forename: Carolyn
authors.initials: C
authors.lastname: Ellaway
authors.forename: Janice
authors.initials: J
authors.lastname: Fletcher
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Kirk
authors.forename: Barry
authors.initials: B
authors.lastname: Lewis
authors.forename: Jim
authors.initials: J
authors.lastname: McGill
authors.forename: Heidi
authors.initials: H
authors.lastname: Peters
authors.forename: James
authors.initials: J
authors.lastname: Pitt
authors.forename: Enzo
authors.initials: E
authors.lastname: Ranieri
authors.forename: Joy
authors.initials: J
authors.lastname: Yaplito-Lee
authors.forename: Avihu
authors.initials: A
authors.lastname: Boneh
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency; D001315:Australia; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D002658:Developmental Disabilities / Q000175:diagnosis / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D015997:Neonatal Screening / Q000379:methods* / Q000639:trends; D011237:Predictive Value of Tests; D053719:Tandem Mass Spectrometry
chemical_list: D042964:Acyl-CoA Dehydrogenase