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. CONCLUSION: Screening by tandem mass spectrometry provides a better outcome for patients at 6 years of age, with fewer deaths and fewer clinically significant disabilities.

[1]  N. Holtzman.  Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress. , 2004, The Journal of pediatrics.

[2]  J. Christodoulou,et al.  Glutaric aciduria type I: outcome following detection by newborn screening , 2008, Journal of Inherited Metabolic Disease.

[3]  K. Bhattacharya,et al.  Newborn screening may fail to identify intermediate forms of maple syrup urine disease , 2006, Journal of Inherited Metabolic Disease.

[4]  S. Edland,et al.  A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening. , 2004, American journal of human genetics.

[5]  K. Gibson,et al.  Mutations in the AUH gene cause 3‐methylglutaconic aciduria type I , 2003, Human mutation.

[6]  R. Norman,et al.  International perspectives on the cost-effectiveness of tandem mass spectrometry for rare metabolic conditions. , 2009, Health policy.

[7]  P. Rinaldo,et al.  Making the case for objective performance metrics in newborn screening by tandem mass spectrometry. , 2006, Mental retardation and developmental disabilities research reviews.

[8]  R. Pollitt.  International perspectives on newborn screening , 2006, Journal of Inherited Metabolic Disease.

[9]  J. Fletcher,et al.  Newborn screening for 3‐methylcrotonyl‐CoA carboxylase deficiency: population heterogeneity of MCCA and MCCB mutations and impact on risk assessment , 2006, Human mutation.

[10]  Michael S. Watson,et al.  Newborn Screening: Toward a Uniform Screening Panel and System—Executive Summary , 2006, Pediatrics.

[11]  Martin Lindner,et al.  Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications. , 2003, Pediatrics.

[12]  J. Vockley,et al.  Short-chain acyl-coenzyme A dehydrogenase deficiency. , 2008, Molecular genetics and metabolism.

[13]  American College of Medical Genetics Newborn Screening Expert Group. Newborn Screening: Toward a Uniform Screening Panel and System—Executive Summary. PEDIATRICS 2006;117:S296–S307. , 2006, Pediatrics.

[14]  A. Boneh,et al.  Newborn screening for glutaric aciduria type I in Victoria: treatment and outcome. , 2008, Molecular genetics and metabolism.

[15]  B. Wilcken,et al.  Newborn screening with tandem mass spectrometry: 12 months' experience in NSW Australia , 1999, Acta paediatrica (Oslo, Norway : 1992). Supplement.

[16]  I. Knerr,et al.  Reduced incidence of severe metabolic crisis or death in children with medium chain acyl-CoA dehydrogenase deficiency homozygous for c.985A>G identified by neonatal screening. , 2005, Molecular genetics and metabolism.

[17]  D. Millington,et al.  The tandem mass spectrometry newborn screening experience in North Carolina: 1997–2005 , 2006, Journal of Inherited Metabolic Disease.

[18]  E. Puffenberger,et al.  Type I glutaric aciduria, part 1: Natural history of 77 patients , 2003, American journal of medical genetics. Part C, Seminars in medical genetics.

[19]  J. Häberle,et al.  Mild citrullinemia in Caucasians is an allelic variant of argininosuccinate synthetase deficiency (citrullinemia type 1). , 2003, Molecular genetics and metabolism.

[20]  B. Wilcken,et al.  Screening newborns for inborn errors of metabolism by tandem mass spectrometry. , 2003, The New England journal of medicine.

[21]  J. Svedmyr,et al.  Systemic effects of a short course of betamethasone compared with high‐dose inhaled budesonide in early childhood asthma , 1999, Acta paediatrica.

[22]  J. Zschocke,et al.  Decline of Acute Encephalopathic Crises in Children with Glutaryl-CoA Dehydrogenase Deficiency Identified by Newborn Screening in Germany , 2007, Pediatric Research.

[23]  R. Fingerhut,et al.  Maple syrup urine disease: Favourable effect of early diagnosis by newborn screening on the neonatal course of the disease , 2006, Journal of Inherited Metabolic Disease.

[24]  J. Fletcher,et al.  Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency in Australia: a cohort study , 2007, The Lancet.

[25]  R. Norman,et al.  Economic Evaluation of Tandem Mass Spectrometry Newborn Screening in Australia , 2009, Pediatrics.

[26]  A F Roche,et al.  CDC growth charts: United States. , 2000, Advance data.