Hammond K B, Abman S H, Sokol R J, Accurso F J
Department of Pediatrics, University of Colorado School of Medicine, Denver 80262.
N Engl J Med. 1991 Sep 12;325(11):769-74. doi: 10.1056/NEJM199109123251104.
To evaluate the feasibility and efficacy of measuring immunoreactive trypsinogen in blood to screen for cystic fibrosis, we performed this test in 279,399 newborns in Colorado from 1982 to 1987.
Immunoreactive trypsinogen was measured in dried blood spots when the infants were 1 to 4 days old; if the level was elevated (greater than or equal to 140 micrograms per liter), the measurement was repeated (mean age, 38 days); if the level was again elevated, sweat testing was performed (mean age, 49 days). For the second test, two cutoff levels (120 and 80 micrograms per liter) were evaluated.
We found an incidence of cystic fibrosis of 1 in 3827 (0.26 per 1000), with 3.2 newborns per 1000 requiring repeat measurement. When adjusted for race and compliance with testing, the incidence among the white infants (1 in 2521) was close to the expected incidence. The false positive rate with the initial cutoff level (92.2 percent) was similar to the rate found in neonatal screening programs for other diseases. False negative results occurred because of laboratory error or changes in procedure (three infants) and trypsinogen concentrations lower than the initial cutoff level (three infants) or lower than the remeasurement cutoff level of 120 micrograms per liter (one infant). Sweat tests were negative in 168 infants with an elevated initial trypsinogen level but a level below 80 micrograms per liter on remeasurement, confirming the value of 80 micrograms per liter as an appropriate cutoff for repeat-test results. Overall, 95.2 percent of the infants with cystic fibrosis (95 percent confidence interval, 85 to 99 percent) who did not have meconium ileus could be identified with the use of a trypsinogen cutoff level of 140 micrograms per liter on initial testing and 80 micrograms per liter on repeat testing.
Statewide screening for cystic fibrosis based on measurements of immunoreactive trypsinogen in dried blood spots is feasible and can be implemented with acceptable rates of repeat testing and false positive and false negative results.
为评估检测血液中免疫反应性胰蛋白酶原以筛查囊性纤维化的可行性和有效性，我们于1982年至1987年在科罗拉多州的279,399名新生儿中开展了此项检测。
在婴儿1至4日龄时检测干血斑中的免疫反应性胰蛋白酶原；若水平升高（大于或等于140微克/升），则重复检测（平均年龄38天）；若水平再次升高，则进行汗液检测（平均年龄49天）。对于第二次检测，评估了两个临界值水平（120和80微克/升）。
我们发现囊性纤维化的发病率为1/3827（0.26/1000），每1000名新生儿中有3.2名需要重复检测。经种族和检测依从性校正后，白人婴儿中的发病率（1/2521）接近预期发病率。初始临界值水平时的假阳性率（92.2%）与其他疾病新生儿筛查项目中的假阳性率相似。出现假阴性结果的原因包括实验室误差或检测程序变更（3例婴儿）、胰蛋白酶原浓度低于初始临界值水平（3例婴儿）或低于重新检测临界值水平120微克/升（1例婴儿）。168例初始胰蛋白酶原水平升高但重新检测时水平低于80微克/升的婴儿汗液检测结果为阴性，证实80微克/升作为重复检测结果的合适临界值是有价值的。总体而言，对于没有胎粪性肠梗阻的囊性纤维化婴儿，使用初始检测胰蛋白酶原临界值水平140微克/升和重复检测临界值水平80微克/升，可识别出95.2%的患儿（95%置信区间，85%至99%）。
基于检测干血斑中免疫反应性胰蛋白酶原进行全州范围的囊性纤维化筛查是可行的，且可在可接受的重复检测率以及假阳性和假阴性结果发生率的情况下实施。
