Bialk Eric R, Lasarev Michael R, Held Patrice K
Wisconsin State Laboratory of Hygiene, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
Int J Neonatal Screen. 2019 Sep 6;5(3):33. doi: 10.3390/ijns5030033. eCollection 2019 Sep.
Newborn screening for congenital adrenal hyperplasia (CAH) has one of the highest false positive rates of any of the diseases on the Wisconsin panel. This is largely due to the first-tier immune assay cross-reactivity and physiological changes in the concentration of 17-hydroxyprogesterone during the first few days of life. To improve screening for CAH, Wisconsin developed a second-tier assay to quantify four different steroids (17-hydroxyprogesterone, 21-deoxycortisol, androstenedione, and cortisol) by liquid chromatography-tandem mass spectrometry (LC-MSMS) in dried blood spots. From validation studies which included the testing of confirmed CAH patients, Wisconsin established its own reporting algorithm that incorporates steroid concentrations as well as two different ratios-the birth weight and the collection time-to identify babies at risk for CAH. Using the newly developed method and algorithm, the false positive rate for the CAH screening was reduced by 95%. Patients with both classical forms of CAH, salt-wasting and simple virilizing, were identified. This study replicates and expands upon previous work to develop a second-tier LC-MSMS steroid profiling screening assay for CAH. The validation and prospective study results provide evidence for an extensive reporting algorithm that incorporates multiple steroids, birth weight, and collection times.
新生儿先天性肾上腺皮质增生症（CAH）筛查的假阳性率在威斯康星州检测的所有疾病中位居前列。这主要归因于一级免疫测定的交叉反应以及出生后几天内17-羟孕酮浓度的生理变化。为改进CAH筛查，威斯康星州开发了一种二级检测方法，通过液相色谱-串联质谱法（LC-MSMS）对干血斑中的四种不同类固醇（17-羟孕酮、21-脱氧皮质醇、雄烯二酮和皮质醇）进行定量。通过包括对确诊CAH患者进行检测的验证研究，威斯康星州建立了自己的报告算法，该算法纳入了类固醇浓度以及两个不同的比率——出生体重和采集时间，以识别有CAH风险的婴儿。使用新开发的方法和算法，CAH筛查的假阳性率降低了95%。同时识别出了患有经典型CAH（失盐型和单纯男性化型）的患者。本研究重复并扩展了先前的工作，开发了一种用于CAH的二级LC-MSMS类固醇谱筛查检测方法。验证和前瞻性研究结果为一种纳入多种类固醇、出生体重和采集时间的广泛报告算法提供了证据。
