Background: Newborn screening for congenital adrenal hyperplasia (CAH) based on 17-OHP concentration in dried blood spots has been taking place in North Eastern Italy since 2001. Since 2017, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been introduced, for the first time in Italy, as a second tier test. Aims: Our study aims to evaluate, on the one hand, the effectiveness of the newborn screening for CAH after 20 years of testing and, on the other, the impact that the introduction of the second tier test had on the diagnostic accuracy of the screening program. Method and Materials: Since 2001 dried blood spots taken from newborns have been screened with a time-resolved fluoroimmunoassay for 17-OHP determination. Over the years, the cut-off levels of 17-OHP were adjusted according to gestational age (GA). Since 2017, a second tier test in LC/MSMS was introduced for samples displaying fluoroimmunoassay 17-OHP exceeding the cut-off. Results: 862.521 newborns have been screened over a period of twenty years. The total incidence of 21-hydroxylase deficiency (21-OHD) was 1:25.368, moreover a case of 11-β-hydroxylase deficiency was identified. All these diagnosis were genetically confirmed. Sensitivity and specificity of the screening program were 97% and 99.4%, respectively. The use of LC-MS/MS as second tier test significantly reduced the recall rate and increased the positive predictive value. Conclusions: Screening for CAH is useful in the neonatal diagnosis of classic form of 21-OHD, allowing a precocious treatment of affected children. The introduction of a LC-MS/MS second tier reduced the recall rate, avoiding unnecessary blood withdraws and medical evaluations and preventing stress to families. Furthermore, it helped identify rarer forms of CAH.


中文翻译：

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意大利东北部先天性肾上腺皮质增生症新生儿筛查 20 年：LC-MS/MS 作为二级检测的作用

背景：自 2001 年以来，意大利东北部一直在开展基于干血斑中 17-OHP 浓度的新生儿先天性肾上腺增生 (CAH) 筛查。自 2017 年以来，液相色谱-串联质谱 (LC-MS/MS)首次在意大利引入，作为二级测试。目的：我们的研究一方面旨在评估经过 20 年检测后新生儿 CAH 筛查的有效性，另一方面评估引入第二级检测对筛查诊断准确性的影响程序。方法和材料：自 2001 年以来，从新生儿身上采集的干血斑已通过时间分辨荧光免疫测定法进行筛查，以测定 17-OHP。多年来，根据胎龄 (GA) 调整了 17-OHP 的临界水平。自 2017 年以来，对显示荧光免疫测定 17-OHP 超过临界值的样品引入了 LC/MSMS 的第二层测试。结果：在 20 年间筛查了 862.521 名新生儿。21-羟化酶缺乏症（21-OHD）的总发病率为1：25.368，此外还发现了1例11-β-羟化酶缺乏症。所有这些诊断都得到了基因证实。筛查方案的敏感性和特异性分别为 97% 和 99.4%。使用 LC-MS/MS 作为第二层测试显着降低了召回率并提高了阳性预测值。结论：CAH 筛查可用于新生儿诊断经典型 21-OHD，从而可以对受影响的儿童进行早熟治疗。LC-MS/MS 第二层的引入降低了召回率，避免不必要的抽血和医疗评估，并防止给家人带来压力。此外，它有助于识别更罕见的 CAH 形式。