Newborn screening for cystic fibrosis in Wisconsin: Comparison of biochemical and molecular methods
Newborn screening for cystic fibrosis in Wisconsin: Comparison of biochemical and molecular methods
复制标题
DOI：
10.1542/peds.99.6.819
复制
发表时间：
1997-06-01
期刊：
影响因子：
8
通讯作者：
Splaingard, M
中科院分区：
文献类型：
--
作者：
Gregg, RG;Simantel, A;Splaingard, M
目标.评估威斯康星州过去10年来新生儿囊性纤维化（CF）筛查的情况，包括对筛查程序和假阳性婴儿特征的研究。从最初设计演变而来的一个重要目标是比较单层免疫反应性胰蛋白酶原（IRT）筛选方法与使用IRT的双层方法的使用，并分析样本中最常见的囊性纤维化跨膜调节因子（CFTR）（Delta F508）突变。我们还检查了在筛选方案中包括多达10个额外CFTR突变的益处。从1985年至1994年，使用IRT或IRT/DNA方案，分别对220862和104308例新生儿进行CF筛查。对于IRT方案，IRT大于或等于180 ng/mL的新生儿被视为阳性，并进行标准汗液氯化物试验以确定CF状态。对于IRT/DNA方案，对IRT大于或等于110 ng/mL的新生儿的古特里卡上的原始干血标本进行检测，以确定是否存在Delta F508 CFTR等位基因，如果DNA检测显示一个或两个Delta F508等位基因，则进行汗液检测。这两种筛选方法都具有很高的特异性。IRT/DNA方案的敏感性往往更高，但差异无统计学意义。IRT/DNA筛选方案的阳性预测值为15.2%，而如果用IRT方法筛选相同的样本，阳性预测值为6.4%。对IRT/DNA假阳性人群的评估显示，双层方法消除了Apgar评分低的婴儿数量不成比例，以及我们先前对IRT水平高的新生儿研究中确定的非洲裔美国人的高患病率。我们发现55%的DNA阳性CF婴儿是Delta F508纯合子，40%有一个Delta F508等位基因。增加10个CFTR突变的分析对灵敏度的影响很小，但可能会显着增加筛查成本。与IRT分析相比，IRT/DNA方案的优势包括提高阳性预测值，减少假阳性婴儿，以及消除召回样本的更快速诊断。
Objectives. To evaluate neonatal screening for cystic fibrosis (CF), including study of the screening procedures and characteristics of false-positive infants, over the past 10 years in Wisconsin. An important objective evolving from the original design has been to compare use of a single-tier immunoreactive trypsinogen (IRT) screening method with that of a two-tier method using IRT and analyses of samples for the most common cystic fibrosis transmembrane regulator (CFTR) (Delta F508) mutation. We also examined the benefit of including up to 10 additional CFTR mutations in the screening protocol.Methods. From 1985 to 1994, using either the IRT or IRT/DNA protocol, 220 862 and 104 308 neonates, respectively, were screened for CF. For the IRT protocol, neonates with an IRT greater than or equal to 180 ng/mL were considered positive, and the standard sweat chloride test was administered to determine CF status. For the IRT/DNA protocol, samples from the original dried-blood specimen on the Guthrie card of neonates with an IRT greater than or equal to 110 ng/mL were tested for the presence of the Delta F508 CFTR allele, and if the DNA test revealed one or two Delta F508 alleles, a sweat test was obtained.Results. Both screening procedures had very high specificity. The sensitivity tended to be higher with the IRT/DNA protocol, but the differences were not statistically significant. The positive predictive value of the IRT/DNA screening protocol was 15.2% compared with 6.4% if the same samples had been screened by the IRT method. Assessment of the false-positive IRT/DNA population revealed that the two-tier method eliminates the disproportionate number of infants with low Apgar scores and also the high prevalence of African-Americans identified previously in our study of newborns with high IRT levels. We found that 55% of DNA-positive CF infants were homozygous for Delta F508 and 40% had one Delta F508 allele. Adding analyses for 10 more CFTR mutations has only a small effect on the sensitivity but is likely to add significantly to the cost of screening.Conclusions. Advantages of the IRT/DNA protocol over IRT analysis include improved positive predictive value, reduction of false-positive infants, and more rapid diagnosis with elimination of recall specimens.