Pediatric Division, Department of Pediatrics, University Hospital of Verona, Verona, Italy.
Pediatric Section, Department Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.
Horm Res Paediatr. 2022;95(3):255-263. doi: 10.1159/000524170. Epub 2022 Mar 29.
Newborn screening for congenital adrenal hyperplasia (CAH) based on 17-hydroxyprogesterone (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.
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.
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. Since 2017, a second-tier test in LC-MS/MS was introduced for samples displaying fluoroimmunoassay 17-OHP exceeding the cut-off.
In total, 862,521 newborns have been screened over a period of 20 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 diagnoses were genetically confirmed. The sensitivity and specificity of the screening program were 97% and 99.4%, respectively. The use of LC-MS/MS as a second-tier test significantly reduced the recall rate and increased the positive predictive value.
Screening for CAH is useful in the neonatal diagnosis of a classic form of 21-OHD, allowing a precocious treatment of affected children. The introduction of an LC-MS/MS second-tier reduced the recall rate, avoiding unnecessary blood withdrawal and medical evaluations and preventing stress to families. Furthermore, it helped identify rarer forms of CAH.
自 2001 年以来，意大利东北部一直在通过干血斑中 17-羟孕酮（17-OHP）浓度对先天性肾上腺皮质增生症（CAH）进行新生儿筛查。自 2017 年以来，液相色谱-串联质谱法（LC-MS/MS）首次在意大利被用作二线检测。
本研究旨在一方面评估 20 年检测后的 CAH 新生儿筛查的有效性，另一方面评估二线检测的引入对筛查计划诊断准确性的影响。
自 2001 年以来，通过时间分辨荧光免疫分析法测定干血斑中的 17-OHP，对新生儿进行筛查。多年来，根据胎龄调整 17-OHP 的截止值。自 2017 年以来，对于荧光免疫分析法 17-OHP 超过截止值的样本，引入了 LC-MS/MS 二级检测。
在 20 年的时间里，共对 862521 名新生儿进行了筛查。21-羟化酶缺乏症（21-OHD）的总发病率为 1:25368，此外还发现了 1 例 11-β-羟化酶缺乏症。所有这些诊断均经基因证实。筛查方案的敏感性和特异性分别为 97%和 99.4%。LC-MS/MS 作为二线检测的使用显著降低了召回率并提高了阳性预测值。
CAH 的筛查有助于新生儿 21-OHD 经典型的诊断，从而可以对受影响的儿童进行早期治疗。二线检测 LC-MS/MS 的引入降低了召回率，避免了不必要的采血和医疗评估，防止了对家庭的压力。此外，它还帮助识别了更罕见的 CAH 形式。
