van der Kamp Hetty J, Wit Jan M
Department of Paediatrics, Leiden University Medical Center, Leiden, The Netherlands.
Eur J Endocrinol. 2004 Nov;151 Suppl 3:U71-5. doi: 10.1530/eje.0.151u071.
Congenital adrenal hyperplasia (CAH) is well suited for newborn screening, as it is a common and potentially fatal disease which can be easily diagnosed by a simple hormonal measurement in blood. Moreover, early recognition and treatment can prevent severe salt wasting, dehydration and death and shorten the time of male sex assignment in virilised females.In screening programmes, 17alpha-hydroxyprogesterone (17OHP) is measured in filter paper blood spots obtained by a heel puncture preferably between 2 and 4 days after birth. Three assay techniques are utilised for initial screening: radio-immunoassay (USA), enzyme-linked immunosorbent assay (Japan) and time-resolved fluoro-immunoassay (Europe). Preterm newborns have higher 17OHP concentrations in serum than babies born at term. Therefore, cut-off levels are based on gestational age (in Japan and Europe) or on birth weight (in the USA). There is a considerable variation in cut-off levels from one programme to another. This is most likely due to the different antibodies and reagents used, varying thickness and density of filter paper used for sample collection and, most significantly, the characteristics of the reference population (in terms of birth weight and gestational age). More than 30 million newborns have been screened. The prevalence of CAH in the USA and Europe is approximately 1:15 000-16 000, and slightly lower in Japan (1:19 000). In general, severe salt wasting can be prevented, but there is a remarkable variation in the number of false-positives and false-negatives among the various programmes. Ongoing refinement of cut-off levels is needed to improve specificity and sensitivity.
先天性肾上腺增生症(CAH)非常适合新生儿筛查,因为它是一种常见且可能致命的疾病,通过简单的血液激素检测即可轻松诊断。此外,早期识别和治疗可预防严重的失盐、脱水和死亡,并缩短男性化女性的性别指定时间。在筛查项目中,通常在出生后2至4天通过足跟穿刺采集的滤纸血斑中检测17α-羟孕酮(17OHP)。初始筛查采用三种检测技术:放射免疫测定法(美国)、酶联免疫吸附测定法(日本)和时间分辨荧光免疫测定法(欧洲)。早产儿血清中的17OHP浓度高于足月儿。因此,临界值水平是基于胎龄(在日本和欧洲)或出生体重(在美国)确定的。不同项目的临界值水平存在相当大的差异。这很可能是由于所使用的抗体和试剂不同、用于样本采集的滤纸厚度和密度不同,以及最重要的是参考人群的特征(出生体重和胎龄方面)不同。已有超过3000万新生儿接受了筛查。美国和欧洲CAH的患病率约为1:15000 - 16000,在日本略低(1:19000)。一般来说,严重的失盐可以预防,但不同项目中的假阳性和假阴性数量存在显著差异。需要不断完善临界值水平以提高特异性和敏感性。