Newborn screening--is it really that simple?

ABSTRACT

The incorporation of tandem mass spectrometry (MSMS) into an existing newborn screening program is an evolving process. Limited worldwide experience has ensured that all stages of reliability testing need to be followed. These include a literature review to establish methodology and analytes/disorders for testing and a pilot screening project including assaying archival samples from subjects with proven target disorders. Algorithms used for analyte concentrations and the relationships of various analytes to one another for resample criteria need to be continually reassessed to maximise screening specificity, sensitivity and positive predictive value. Since 1st of April 1998, the NSW Newborn Screening Program has screened 320, 848 babies using electrospray MSMS for selected amino acids and acyl camitines. Screening for amino acids has led to requests for 415 repeat samples with 94 babies referred for further testing. Of these 73 had a disorder of amino acid metabolism, including 43 with persistent hyperphenylalaninemia (36 of whom had PKU, 2 had a pterin pathway defect, 5 HPAA). Screening for acyl carnitines has led to requests for 245 repeat samples with 63 babies referred for further investigation. Of these 44 had a diagnosed disorder, including 15 with medium chain acyl CoA dehydrogenase deficiency. Five babies with confirmed disorders detectable with MS/MS had negative test results. The cost of screening using MSMS was only $A0.50 more than the method for screening for PKU and homocystinuria alone (ie the bacterial inhibition assays) and has allowed detection of an additional 74 babies at least 48 of whom have a diagnosis for which early treatment seems clearly beneficial. MSMS has shown a sensitivity of 95.9% and specificity of 99.8% in our laboratory with a positive predictive value of 18%.