|Victor R. De Jesus, Joanne V Mei, Nancy K Meredith, Carol J Bell, Timothy L Lim, Barbara W Adam.|
W Harry Hannon Newborn Screening Quality Assurance Program, Centers for Disease Control and Prevention, Atlanta, GA 30341
For more than 30 years the Newborn Screening Quality Assurance Program (NSQAP) at CDC has operated quality control (QC) and proficiency testing (PT) programs for state public health and other domestic and international laboratories, ensuring the quality and accuracy of screening tests for more than 4 million babies each year in the United States alone. Certified QC and PT dried-blood spot (DBS) materials are prepared and distributed to over 400 laboratories in 62 countries. PT materials are available for 48 of 53 primary and secondary disorders listed in the uniform panel for newborn screening recommended by the American College of Medical Genetics (ACMG). The majority of the analytes for these disorders are measured by tandem mass spectrometry (MS/MS), given that the introduction MS/MS-based methods for the detection of phenylalanine in DBS by Chace et al (1993) revolutionized the practice of newborn screening for several amino acid, organic acid and fatty acid oxidation metabolic disorders.
Blinded PT panels were sent quarterly to MS/MS laboratories while QC materials, designed to monitor the long-term stability of assays, were sent two times per year. Qualitative PT results were assessed for false-positive and false-negative errors and bias plots of quantitative PT results were constructed. Using reported QC data, dose response curves, intercepts, and slopes were calculated for individual analytes for method and laboratory comparisons.
In 2008, the domestic false-positive rate was 0.0% to 2.2% and the false-negative rate ranged from 0.0% to 15.2% for disorders measured in PT challenges by MS/MS; for 15 of 20 of these disorders the false-negative rate was 0.0%. Reasonable biases of less than ± 20% of the expected value were achieved for all amino acids and acylcarnitines.
QC and PT services for MS/MS measurements in newborn screening demonstrate the need for surveillance to ensure harmonization and continuous improvements and sustain the high-performance of newborn screening laboratories worldwide.
Acknowledgements: This work was supported by the Centers for Disease Control and Prevention, US Department of Health and Human Services.
Chace DH, Millington DS, Terada N, Kahler SG, Roe CR, Hofman LF. Rapid diagnosis of phenylketonuria by quantitative analysis for phenylalanine and tyrosine in neonatal blood spots by tandem mass spectrometry. Clin Chem 1993; 39(1): 66-71.