Expanded newborn screening: outcome in screened and unscreened patients at age 6 years.
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.
Wilcken
Bridget
B
Department of Biochemical Genetics, Children's Hospital at Westmead, Sydney, Australia. bridgetw@chw.edu.au
Haas
Marion
M
Joy
Pamela
P
Wiley
Veronica
V
Bowling
Francis
F
Carpenter
Kevin
K
Christodoulou
John
J
Cowley
David
D
Ellaway
Carolyn
C
Fletcher
Janice
J
Kirk
Edwin P
EP
Lewis
Barry
B
McGill
Jim
J
Peters
Heidi
H
Pitt
James
J
Ranieri
Enzo
E
Yaplito-Lee
Joy
J
Boneh
Avihu
A
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
D042964:Acyl-CoA Dehydrogenase