Authors' objectives:

This study aims to answer the following research questions : - Should the Guthrie test used in Ontario's neonatal screening program be replaced with tandem mass spectrometer testing (MS/MS)? - Should neonates be screened for additional inborn errors of metabolism (IEMs) using MS/MS?

Authors' results and conclusions: Ontario is currently screening all newborns for phenylketonuria (PKU) and congenital hypothyroidism (CH) using the Guthrie method on dry blood spots obtained by heel prick before discharge from hospital MS/MS can detect 25 IEMs in a single process on the same dry blood spot Computer algorithms have been used to automate the MS/MS screening process to provide rapid throughputs of 400 samples or more per day. Screening for additional IEMs using MS/MS does not add significant cost to the program MS/MS -based neonatal screening showed sensitivity of 100 per cent and specificity of 83 per cent to 99 per cent depending on the IEM. The specificity of MS/MS in detecting PKU is significantly superior to that of the current Guthrie method and is therefore able to reduce the number of false positive results For certain IEMs that are not currently being screened in Ontario, early detection and simple treatment could avoid early mortality and prevent or reduce mental retardation in the affected infants An assessment using eligibility criteria recommended by the World Health Organization showed that PKU and CH should continue to be screened. In addition, MCADD and CAH met most of the eligibility criteria for inclusion in a neonatal screening program. MCADD can be screened with PKU by MS/MS while the CAH requires separate independent testing An expanded neonatal program would require an enhanced infrastructure for result interpretation, reporting, care provision and counseling. Some of these cost are already being incurred for the treatment of children who develop illnesses associated with IEMs that can be effectively screened Important ethical and societal issues including informed consent need to be addressed. As of 1998, twenty-six states in the US were using MS/MS for newborn screening of IEMs. In Canada, British Columbia, Saskatchewan and Nova Scotia use MS/MS for IEM related assays. Manitoba is planning to implement MS/MS-based neonatal screening in 2003. Among Canadian jurisdictions, British Columbia, Manitoba, Quebec, Nova Scotia and Saskatchewan are screening for more IEMs than Ontario.

Authors' recommendations: There are significant societal issues that need to be addressed through an appropriate consultation process on issues including informed consent and testing for IEMs for which there is no effective treatment. There is evidence that expanding neonatal screening to include medium chain acyl-CoA dehydrogenase deficiency (MCADD) will increase the number of inborn errors of metabolism identified and reduce the number of children dying or becoming mentally handicapped as a result of this preventable disease. The MS/MS increases specificity for PKU and therefore offers an advantage over the current Guthrie test. There also seems to be evidence that some of the other IEMs, at least two of which (Tyrosinemia and Glutaric Aciduria Type 1) may have a high incidence in targeted populations in Ontario.

Authors' methods: Systematic review

Project Status: Completed

Year Published: 2003

URL for published report: http://www.health.gov.on.ca/english/providers/program/mas/tech/reviews/pdf/rev_tandms_090102.pdf

URL for additional information: http://www.hqontario.ca/evidence/publications-and-ohtac-recommendations/ohtas-reports-and-ohtac-recommendations/neonatal-screening-of-inborn-errors-of-metabolism-using-tandem-mass-spectrometer

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Canada

Organisation Name: Medical Advisory Secretariat

Contact Address: Medical Advisory Secretariat, 20 Dundas Street West, 10th Floor, Toronto, ON M5G 2N6 CANADA. Tel: 416-314-1092l; Fax: 416-325-2364;

Contact Name: MASinfo.moh@ontario.ca

Contact Email: MASinfo.moh@ontario.ca

Copyright: Medical Advisory Secretariat, Ontario Ministry of Health and Long-Term Care