Department of Research and Innovation, Atrium Medical Centre, Heerlen, The Netherlands. amm.vernooij+
Thorax. 2012 Apr;67(4):289-95. doi: 10.1136/thoraxjnl-2011-200730. Epub 2012 Jan 23.
Newborn screening for cystic fibrosis (CF) is included in many routine programmes but current strategies have considerable drawbacks, such as false-positive tests, equivocal diagnosis and detection of carriers.
To assess the test performance of two newborn screening strategies for CF.
DESIGN, SETTING AND PARTICIPANTS: In 2008 and 2009, CF screening was added to the routine screening programme as a prospective study in part of The Netherlands.
Two strategies were performed in all newborns. In the first strategy, concentrations of immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP) were measured. In the second method, samples with IRT ≥60 μg/litre were analysed for 36 CFTR mutations, followed by sequencing when a single mutation was detected. Tests were positive only with two identified CFTR mutations.
Sensitivity, specificity and positive predictive value (PPV) of both screening strategies.
145,499 infants were screened. The IRT/PAP approach showed a sensitivity of 95.0%, a specificity of 99.897% and a PPV of 12.3%. Test properties for the IRT/DNA/sequencing strategy were respectively 100%, 100% and 64.9%. Combining both strategies (IRT/PAP/DNA/sequencing) led to a sensitivity of 95.0%, a specificity of 100% and a PPV of 87.5%.
In conclusion, all strategies performed well. Although there was no statistically significant difference in test performance, the IRT/DNA/sequencing strategy detected one infant that was missed by IRT/PAP (/DNA/sequencing). IRT/PAP may be the optimal choice if the use of DNA technology must be avoided. If identification of carriers and equivocal diagnosis is considered an important disadvantage, IRT/PAP/DNA/sequencing may be the best choice.
囊性纤维化（CF）的新生儿筛查已纳入许多常规计划中，但当前的策略存在许多缺陷，例如假阳性测试、不确定的诊断和携带者的检测。
评估两种 CF 新生儿筛查策略的检测性能。
设计、设置和参与者：2008 年和 2009 年，CF 筛查作为一项前瞻性研究被添加到荷兰部分地区的常规筛查计划中。
两种策略均在所有新生儿中进行。在第一种策略中，测量免疫反应性胰蛋白酶原（IRT）和胰腺炎相关蛋白（PAP）的浓度。在第二种方法中，当 IRT≥60μg/L 时，对 36 种 CFTR 突变进行分析，然后在检测到单个突变时进行测序。仅当两种鉴定的 CFTR 突变时，测试才为阳性。
两种筛查策略的敏感性、特异性和阳性预测值（PPV）。
共筛查了 145499 名婴儿。IRT/PAP 方法的敏感性为 95.0%，特异性为 99.897%，阳性预测值为 12.3%。IRT/DNA/测序策略的测试特性分别为 100%、100%和 64.9%。结合两种策略（IRT/PAP/DNA/测序）可使敏感性达到 95.0%，特异性达到 100%，阳性预测值达到 87.5%。
综上所述，所有策略的性能都很好。虽然测试性能没有统计学上的显著差异，但 IRT/DNA/测序策略检测到了 IRT/PAP 漏诊的一名婴儿（DNA/测序）。如果必须避免使用 DNA 技术，IRT/PAP 可能是最佳选择。如果认为鉴定携带者和不确定的诊断是一个重要的缺点，那么 IRT/PAP/DNA/测序可能是最佳选择。
