Divisions of Gastroenterology, Hepatology.
Translational Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
Pediatrics. 2021 Dec 1;148(6). doi: 10.1542/peds.2021-051740.
Cystic fibrosis (CF) screen-positive infants with an inconclusive diagnosis (CFSPID) are infants in whom sweat testing and genetic analysis does not resolve a CF diagnosis. Lack of knowledge about the health outcome of these children who require clinical follow-up challenges effective consultation. Early predictive biomarkers to delineate the CF risk would allow a more targeted approach to these children.
Prospective, longitudinal, multicenter, Canada-wide cohort study of CF positive-screened newborns with 1 to 2 cystic fibrosis transmembrane conductance regulator gene variants, of which at least 1 is not known to be CF-causing and/or a sweat chloride between 30 and 59 mmol/L. These were monitored for conversion to a CF diagnosis, pulmonary, and nutritional outcomes.
The mean observation period was 7.7 (95% confidence interval 7.1 to 8.4) years. A CF diagnosis was established for 24 of the 115 children with CFSPID (21%) either because of reinterpretation of the cystic fibrosis transmembrane conductance regulator genotype or because of increase in sweat chloride concentration ≥60 mmol/L. An initial sweat chloride of ≥40 mmol/l predicted conversion to CF on the basis of sweat testing. The 91 remaining children with CFSPID were pancreatic sufficient and showed normal growth until school age. Pulmonary function as well as lung clearance index in a subgroup of children with CFSPID were similar to that of healthy controls.
Children with CFSPID have good nutritional and pulmonary outcomes at school age, but rates of reclassifying the diagnosis are high. The initial sweat chloride test can be used as a biomarker to predict the risk for CF in CFSPID.
囊性纤维化（CF）筛查阳性且诊断不确定的婴儿（CFSPID）是指汗液检测和基因分析无法明确 CF 诊断的婴儿。由于这些需要临床随访的儿童缺乏相关知识，导致有效咨询面临挑战。缺乏能够明确 CF 风险的早期预测生物标志物，也使得无法对这些儿童采取更有针对性的方法。
这是一项前瞻性、纵向、多中心、加拿大范围内的 CF 阳性筛查新生儿队列研究，这些新生儿的 1 至 2 个囊性纤维化跨膜电导调节基因变异，其中至少 1 个变异不被认为是 CF 致病突变，且汗液氯化物浓度在 30 至 59mmol/L 之间。这些婴儿被监测是否会转为 CF 诊断、肺部和营养状况。
平均观察期为 7.7 年（95%置信区间 7.1 至 8.4）。115 例 CFSPID 中有 24 例（21%）被诊断为 CF，其原因要么是重新解读囊性纤维化跨膜电导调节基因谱，要么是汗液氯化物浓度增加≥60mmol/L。初始汗液氯化物≥40mmol/L可预测基于汗液检测的 CF 转化。其余 91 例 CFSPID 儿童胰腺功能充足，在上学前生长发育正常。CFSPID 儿童的肺功能以及肺清除指数与健康对照组相似。
CFSPID 儿童在上学时具有良好的营养和肺部预后，但重新诊断的比例较高。初始汗液氯化物检测可作为 CFSPID 中 CF 风险的预测生物标志物。
