Neonatal screening of inborn errors of metabolism using tandem mass spectrometry: an evidence-based analysis

Abstract

Objectives and method: The Medical Advisory Secretariat undertook a review of the evidence on the effectiveness and cost-effectiveness of using tandem mass spectrometer [MS/MS] for the neonatal screening of inborn errors of metabolism [IEM]. The review is based on two systematic reviews commissioned by the National Health Services (United Kingdom) and relevant research literature that was published after the completion of these two systematic reviews. A horizon scanning was conducted to determine the current status of neonatal screening programs in other national and international jurisdictions. The MAS also consulted with stakeholders including the laboratory branch, an expert in IEM at a pediatric hospital, MS/MS experts and a MS/MS manufacturer.

Result: Synthesis of information obtained from the above process showed that: 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% and specificity of 83% to 99% 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 inborn errors of metabolism not currently screened, early detection and simple treatment could avoid early mortality and prevent or reduce mental retardationUsing eligibility criteria recommended by the World Health Organization adapted to Ontario, a rating system was developed and applied to assess the IEMs recommended for inclusion in neonatal screening.The assessment showed that PKU and CH should continued to be screened. In addition, medium chain acyl-CoA dehydrogenase deficiency [MCADD] and congenital adrenal hyperplasia [CAH] met most of the criteria for inclusion in a neonatal screening program. MCADD can be screened with PKU by MS/MS while the test for CAH requires a different methodology.An expanded neonatal program would require an enhanced infrastructure for result interpretation, reporting, care provision and counseling.Important ethical and societal issues including informed consent need to be addressed.As of 1998, twenty-six states in the United States 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.