Steroid profiling by tandem mass spectrometry improves the positive predictive value of newborn screening for congenital adrenal hyperplasia.
Congenital adrenal hyperplasia (CAH) is primarily caused by 21-hydroxylase deficiency and leads to an accumulation of 17-hydroxyprogesterone and reduced cortisol levels. Newborn screening for CAH is traditionally based on measuring 17-hydroxyprogesterone by different immunoassays. Despite attempts to adjust cutoff levels for birth weight, gestational age, and stress factors, the positive predictive value for CAH screening remains less than 1%. To improve this situation, we developed a method using liquid chromatography-tandem mass spectrometry to measure 17-hydroxyprogesterone, androstenedione, and cortisol simultaneously in blood spots. A total of 1222 leftover blood spots from six different screening programs using different immunoassays (fluorescent immunoassay and ELISA) were reanalyzed in a blinded fashion by liquid chromatography-tandem mass spectrometry. Thirty-one samples were from babies with CAH, 190 had yielded false-positive results by immunoassay, and the remaining 1001 samples were from babies with normal screening results. Steroid profiling allowed for an elimination of 169 (89%) of the false-positive results and for an improvement of the positive predictive value from the reported 0.5 to 4.7%. Although this method is not suitable for mass screening due to the length of the analysis (12 min), it can be used as a second-tier test of blood spots with positive results for CAH by the conventional methods. This would prevent unnecessary blood draws, medical evaluations, and stress to families.
Minutti
Carla Z
CZ
Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Lacey
Jean M
JM
Magera
Mark J
MJ
Hahn
Si Houn
SH
McCann
Mark
M
Schulze
Andreas
A
Cheillan
David
D
Dorche
Claude
C
Chace
Donald H
DH
Lymp
James F
JF
Zimmerman
Donald
D
Rinaldo
Piero
P
Matern
Dietrich
D
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood*; D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis*; D000735:Androstenedione / Q000097:blood*; D002853:Chromatography, Liquid; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007231:Infant, Newborn; D013058:Mass Spectrometry / Q000379:methods*; D015997:Neonatal Screening / Q000379:methods* / Q000592:standards*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016037:Single-Blind Method
D000735:Androstenedione; D019326:17-alpha-Hydroxyprogesterone; D006854:Hydrocortisone