Comparison of Newborn Screening Protocols for Congenital Adrenal Hyperplasia in Preterm Infants

• Published in: The Journal of pediatrics Vol. 164; no. 5; pp. 1136 - 1140
• Main Authors: Sarafoglou, Kyriakie, MD, Gaviglio, Amy, MS, CGC, Hietala, Amy, MS, Frogner, Garen, BS, Banks, Kathryn, BA, McCann, Mark, BS, Thomas, William, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2014
• Subjects: Adrenal Hyperplasia, Congenital - blood; Adrenal Hyperplasia, Congenital - diagnosis; Biomarkers - blood; Chromatography, Liquid; Clinical Protocols; Dried Blood Spot Testing - methods; False Positive Reactions; Fluoroimmunoassay; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases - blood; Infant, Premature, Diseases - diagnosis; Neonatal Screening - methods; Pediatrics; Predictive Value of Tests; Steroids - blood; Tandem Mass Spectrometry - methods; 17-hydroxyprogesterone; False positive; FN; FPR; Liquid chromatography-tandem mass spectrometry; NICU; FP; CAH; False positive rate; LC-MS/MS; True positive; False negative; Neonatal intensive care unit; PPV; Newborn screening; Positive predictive value; Congenital adrenal hyperplasia; TP; 17OHP; Fluoroimmunoassay; NBS; FIA
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2014.01.038

Objective To compare 2 screening protocols performed concurrently in Minnesota: (1) liquid chromatography tandem mass spectrometry steroid profiling as a second-tier test on positive fluoroimmunoassay (FIA) results; and (2) low-birthweight 3-screen protocol (FIA tests at <48 hours, 2 weeks, 4 weeks) on all infants <1800 g, regardless of result. Study design Population-based study of all <1800 g infants (n = 8739) born in Minnesota from 2004-2010 comparing newborn screening performance metrics of 2-tier (FIA + liquid chromatography tandem mass spectrometry) protocol (2004-2010) vs 1-tier (FIA) low-birthweight 3-screen protocol (2006-2010). False positive (FP) rates were calculated per infant's final confirmatory result. Protocol results used in different time periods (2004-2005 vs 2006-2010) were compared by 2-sample tests of proportions; results of both protocols for 2006-2010 were compared by McNemar test. Results First-tier testing of final dried blood spot result (n = 6625) of the low-birthweight 3-screen protocol during 2006-2010 reduced the FP rate more than 5-fold ( P  < .0001) compared with 2-tier testing of a single dried blood spot (n = 2114) from 2004-2005. In comparing results (n = 6625) of both protocols from 2006-2010, first-tier testing of final dried blood spot accounted for 23% of FPs; second-tier testing of the first dried blood spot accounted for 77%, yielding significantly more FP results (McNemar test, P  < .0001). Conclusion Timing of dried blood spot collection rather than assay used played a more important role in reducing FP results of congenital adrenal hyperplasia newborn screening in low birthweight infants.