Reduction of the false‐positive rate in newborn screening by implementation of MS/MS‐based second‐tier tests: The Mayo Clinic experience (2004–2007)

• Published in: Journal of inherited metabolic disease Vol. 30; no. 4; pp. 585 - 592
• Main Authors: Matern, D., Tortorelli, S., Oglesbee, D., Gavrilov, D., Rinaldo, P.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.08.2007; Blackwell Publishing Ltd
• Subjects: Adrenal Hyperplasia, Congenital - blood; Adrenal Hyperplasia, Congenital - diagnosis; False Positive Reactions; Homocystinuria - blood; Homocystinuria - diagnosis; Humans; Infant, Newborn; Maple Syrup Urine Disease - blood; Maple Syrup Urine Disease - diagnosis; Mass Spectrometry - methods; Neonatal Screening - methods; Predictive Value of Tests; Sensitivity and Specificity; Time Factors; Tyrosinemias - blood; Tyrosinemias - diagnosis; Vitamin B 12 Deficiency - blood; Vitamin B 12 Deficiency - diagnosis
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-007-0691-y

Summary The continued expansion of newborn screening programmes to include additional conditions increases the responsibility of newborn screening laboratories to provide testing with the highest sensitivity and specificity to allow for identification of affected patients while minimizing the false‐positive rate. Some assays and analytes are particularly problematic. Over recent years, our laboratory tried to improve this situation by developing second‐tier tests to reduce false‐positive results in the screening for congenital adrenal hyperplasia (CAH), tyrosinaemia type I, methylmalonic acidaemias, homocystinuria, and maple syrup urine disease (MSUD). Beginning in 2004, this approach was applied to Mayo's newborn screening programme and resulted in a false‐positive rate of 0.09%, a positive predictive value of 41%, and a positive detection rate of 1 affected case in 1672 babies screened.