Elsevier

Pathology

Volume 40, Issue 2, February 2008, Pages 104-115
Pathology

Newborn screening

https://doi.org/10.1080/00313020701813743Get rights and content

Summary

The aim of newborn screening is to detect newborns with serious, treatable disorders so as to facilitate appropriate interventions to avoid or ameliorate adverse outcomes. Mass biochemical testing of newborn babies was pioneered in the 1960s with the introduction of screening for phenylketonuria, a rare inborn error of metabolism, tested by using a dried blood spot sample. The next disorder introduced into screening programs was congenital hypothyroidism and a few more much rarer disorders were gradually included.

Two recent advances have greatly changed the pace: modification of tandem mass spectrometry and DNA extraction and analysis from newborn screening dried blood spot. These two technologies make the future possibilities of newborn screening seem almost unlimited.

Newborn screening tests are usually carried out on a dried blood spot sample, for which there are special analytical considerations. Dried blood spot calibrators and controls, prepared on the same lot number of filter paper, are needed. Methods have a co-efficient of variation of about 10% due to the increased variability of a dried filter paper sample compared with other biochemical samples. The haematocrit is an additional variable not able to be measured. Also of importance is obtaining a balance between the sensitivity and specificity of each assay. Fixing cut-off points for action needs consideration of what is an acceptable percentage of the population to recall for further testing. Few assays are 100% discriminatory.

Programs in Australasia currently screen for at least 30 disorders. Detection of these requires not only the assay of a primary marker but often determination of a ratio of that marker with another, or possibly an alternative assay, for example a DNA mutation. The most important disorders screened for are described briefly: phenylketonuria, primary congenital hypothyroidism, cystic fibrosis, the galactosaemias, medium-chain acyl-CoA dehydrogenase deficiency, glutaryl-CoA dehydrogenase deficiency and congenital adrenal hyperplasia, together with several other disorders detectable by tandem mass spectrometry.

Newborn screening deals with rare disorders and benefit cannot be shown easily without very large pilot studies. There have been randomised controlled trials of screening for cystic fibrosis, and now several studies are beginning to establish the benefit of tandem mass spectrometry screening for disorders of fatty acid and amino acid metabolism.

Two things will influence the new directions for newborn screening: the development of effective treatments for hitherto untreatable disorders, and advancing technology, enabling new testing strategies to be developed. There are novel treatments on the horizon for many discrete disorders. Susceptibility testing has recently been considered for newborn screening application, but is more controversial. Newborn screening has entered a new and exciting phase, with an explosion of new treatments, new technologies, and, possibly in the future, new preventive strategies.

Reference (74)

  • M. Rauh et al.

    Automated, fast and sensitive quantification of 17 alpha-hydroxy-progesterone, androstenedione and testosterone by tandem mass spectrometry with on-line extraction

    Steroids

    (2006)
  • D.H. Chace et al.

    A biochemical perspective on the use of tandem mass spectrometry for newborn screening and clinical testing

    Clin Biochem

    (2005)
  • B.S. Andresen et al.

    Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency

    Am J Hum Genet

    (2001)
  • B. Wilcken et al.

    Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency: a cohort study

    Lancet

    (2007)
  • U. Nennstiel-Ratzel 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

    Mol Genet Metab

    (2005)
  • P.J. Meikle et al.

    Newborn screening for lysosomal storage disorders

    Mol Genet Metab

    (2006)
  • L.R. Singh et al.

    Chemical chaperone rescue of mutant human cystathionine beta-synthase

    Mol Genet Metab

    (2007)
  • A. Folling

    Uber Ausscheidung von Phenylbrenztraubensaur in den Harn als Stoffwechselanomalie in Verbindung mit Imbezillitat

    Z Physiol Chem

    (1934)
  • L.I. Woolf et al.

    Treatment of phenylketonuria with a diet low in phenylalanine

    Br Med J

    (1955)
  • R. Guthrie et al.

    A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants

    Pediatries

    (1963)
  • R.A. MacCready et al.

    Newborn phenylketonuria detection program in Massachusetts

    Am J Public Health Nations Health

    (1964)
  • J.S. Popkins et al.

    Is hereditary histidinaemia harmful?

    Lancet

    (1974)
  • R. Illig et al.

    Early detection of neonatal hypothyroidism by serial TSH determination in dried blood. Six months experience with a reliable, efficient and inexpensive method

    Helv Paediatr Acta

    (1977)
  • S. Pang et al.

    A pilot newborn screening for congenital adrenal hyperplasia in Alaska

    J Clin Endocrinol Metab

    (1982)
  • S.Y. Pang et al.

    Worldwide experience in newborn screening for classical congential adrenal hyperplasia due to 21-hydroxylase deficiency

    Pediatrics

    (1988)
  • J.R. Crossley et al.

    Dried-blood spot screening for cystic fibrosis in the newborn

    Lancet

    (1979)
  • C.M. Lees et al.

    Neonatal screening for sickle cell disease

    Cochrane Database Syst Rev

    (2000)
  • D.S. Millington et al.

    Tandem mass spectrometry: a new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism

    J Inherit Metab Dis

    (1990)
  • E.R. McCabe et al.

    DNA microextraction from dried blood spots on filter paper blotters: potential applications to newborn screening

    Hum Genet

    (1987)
  • D.M. Bradley et al.

    Experience with screening newborns for Duchenne muscular dystrophy in Wales

    BMJ

    (1993)
  • E.P. Parsons et al.

    Newborn screening for Duchenne muscular dystrophy

    Arch Dis Child

    (2003)
  • T. Yokota et al.

    Potential of oligonucleotide-mediated exon-skipping therapy for Duchenne muscular dystrophy

    Expert Opin Biol Ther

    (2007)
  • S. Aurino et al.

    Readthrough strategies for stop codons in Duchenne muscular dystrophy

    Acta Myol

    (2006)
  • J.MG. Wilson et al.

    Principies and Practice of Screening for Disease.

    Geneva: World Health Organization

    (1968)
  • ACMG Newborn Screening Expert Group. Newborn screening panel and system. Genet Med 2006; 8:...
  • National Screening Committee. Criteria for appraising the viability, effectiveness and appropriateness of a screening...
  • C.R. Scriver et al.

    The Metabolic and Molecular Bases of Inherited Disease.

  • Cited by (0)

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