BACKGROUND AND OBJECTIVES 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

中文翻译：

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学龄期诊断不确定的囊性纤维化筛查阳性婴儿的结果。

背景和目的 囊性纤维化 (CF) 筛查阳性且诊断结果不确定 (CFSPID) 是指汗液检测和基因分析不能解决 CF 诊断的婴儿。缺乏对这些需要临床随访的儿童的健康结果的了解对有效咨询提出了挑战。描述 CF 风险的早期预测性生物标志物将允许对这些儿童采取更有针对性的方法。方法 前瞻性、纵向、多中心、加拿大范围的队列研究，对 CF 阳性筛查的新生儿具有 1 到 2 个囊性纤维化跨膜传导调节基因变异，其中至少 1 个未知是 CF 导致和/或汗液氯化物之间30 和 59 毫摩尔/升。监测这些转化为 CF 诊断、肺部和营养结果。结果 平均观察期为 7。7（95% 置信区间 7.1 到 8.4）年。115 名 CFSPID 儿童中有 24 名 (21%) 确诊为 CF，原因是对囊性纤维化跨膜电导调节基因型的重新解释或汗液氯化物浓度增加≥60 mmol/L。根据汗液测试，≥40 mmol/l 的初始汗液氯化物可预测转化为 CF。剩余的 91 名 CFSPID 儿童胰腺功能充足，并且在学龄前均显示正常生长。CFSPID 儿童亚组的肺功能和肺清除指数与健康对照组相似。结论 患有 CFSPID 的儿童在学龄期具有良好的营养和肺部结局，但重新分类诊断的比率很高。