title: Use of steroid profiling by UPLC-MS/MS as a second tier test in newborn screening for congenital adrenal hyperplasia: the Utah experience.
abstract: Newborn screening allows the diagnosis of congenital adrenal hyperplasia (CAH) before symptoms appear, preventing the severe and potentially life-threatening crisis associated with this disease in infancy. Traditional screening by enzyme immunoassay results in a large number of false positives. To reduce the number of unnecessary tests, anxiety to families and physicians, and the burden to the newborn screening follow-up program, we implemented a second-tier test for CAH using steroid profiling by an ultra-performance liquid chromatography-tandem mass spectrometry. We measured three steroids: 17-hydroxyprogesterone, androstenedione, and cortisol and correlated them with the age of infant at the time of sample collection and birth weight. Both age at collection and birth weight affected the levels of adrenal steroids, but the use of appropriate cut offs and analyte ratios allowed the identification of infants with CAH. This approach was effective in identifying infants with CAH, with both salt-wasting and simple virilizing forms, while reducing the false-positive rate from 2.6 to 0.09%.
authors.affiliation: ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake City, Utah 84108, USA. schwarl@aruplab.com
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schwarz
authors.forename: Aiping
authors.initials: A
authors.lastname: Liu
authors.forename: Harper
authors.initials: H
authors.lastname: Randall
authors.forename: Christa
authors.initials: C
authors.lastname: Haslip
authors.forename: Fay
authors.initials: F
authors.lastname: Keune
authors.forename: Mary
authors.initials: M
authors.lastname: Murray
authors.forename: Nicola
authors.initials: N
authors.lastname: Longo
authors.forename: Marzia
authors.initials: M
authors.lastname: Pasquali
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis*; D000735:Androstenedione / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014589:Utah
chemical_list: D000735:Androstenedione; D019326:17-alpha-Hydroxyprogesterone; D006854:Hydrocortisone