Division of Endocrinology, Department of Pediatrics, University of Minnesota Amplatz Children’s Hospital, Minneapolis, Minnesota 55454, USA.
Pediatrics. 2012 Nov;130(5):e1261-8. doi: 10.1542/peds.2012-1219. Epub 2012 Oct 15.
Newborn screening (NBS) for the classic forms of congenital adrenal hyperplasia (CAH) is mandated in all states in the United States. Compared with other NBS disorders, the false-positive rate (FPR) of CAH screening remains high and has not been significantly improved by adjusting 17α-hydroxyprogesterone cutoff values for birth weight and/or gestational age. Minnesota was the first state to initiate, and only 1 of 4 states currently performing, second-tier steroid profiling for CAH. False-negative rates (FNRs) for CAH are not well known.
This is a population-based study of all Minnesota infants (769,834) born 1999-2009, grouped by screening protocol (one-tier with repeat screen, January 1999 to May 2004; two-tier with second-tier steroid profiling, June 2004 to December 2009). FPR, FNR, and positive predictive value (PPV) were calculated per infant, rather than per sample, and compared between protocols.
Overall, 15 false-negatives (4 salt-wasting, 11 simple-virilizing) and 45 true-positives were identified from 1999 to 2009. With two-tier screening, FNR was 32%, FPR increased to 0.065%, and PPV decreased to 8%, but these changes were not statistically significant. Second-tier steroid profiling obviated repeat screens of borderline results (355 per year average).
In comparing the 2 screening protocols, the FPR of CAH NBS remains high, the PPV remains low, and false-negatives occur more frequently than has been reported. Physicians should be cautioned that a negative NBS does not necessarily rule out classic CAH; therefore, any patient for whom there is clinical concern for CAH should receive immediate diagnostic testing.
美国所有州都要求对经典型先天性肾上腺皮质增生症（CAH）进行新生儿筛查（NBS）。与其他 NBS 疾病相比，CAH 筛查的假阳性率（FPR）仍然较高，并且通过调整出生体重和/或胎龄的 17α-羟孕酮截断值，其 FPR 并未得到显著改善。明尼苏达州是第一个启动、也是目前仅有的 4 个州之一进行 CAH 二级类固醇分析的州。CAH 的假阴性率（FNR）尚不清楚。
这是一项基于人群的研究，研究对象为 1999 年至 2009 年期间出生的所有明尼苏达州婴儿（769834 名），根据筛查方案（1999 年 1 月至 2004 年 5 月的单阶段重复筛查；2004 年 6 月至 2009 年 12 月的双阶段，包括二级类固醇分析）进行分组。FPR、FNR 和阳性预测值（PPV）按婴儿计算，而不是按样本计算，并在不同方案之间进行比较。
总体而言，在 1999 年至 2009 年期间，共发现 15 例漏诊（4 例失盐型，11 例单纯男性化型）和 45 例阳性病例。采用双阶段筛查，FNR 为 32%，FPR 增加至 0.065%，PPV 下降至 8%，但这些变化无统计学意义。二级类固醇分析可避免对边界结果进行重复筛查（每年平均 355 次）。
在比较两种筛查方案时，CAH NBS 的 FPR 仍然较高，PPV 仍然较低，且漏诊比已报道的更为常见。医生应注意，阴性 NBS 不一定排除经典型 CAH；因此，对于任何具有 CAH 临床特征的患者，都应立即进行诊断性检测。
