Sciortino Stanley, Graham Steve, Bishop Tracey
Genetic Disease Screening Program, Center for Family Health, California Department of Public Health, Richmond, CA.
Genetic Disease Screening Program, Center for Family Health, California Department of Public Health, Richmond, CA.
J Pediatr. 2025 Jan;276:114287. doi: 10.1016/j.jpeds.2024.114287. Epub 2024 Sep 2.
To compare the long-term diagnostic transitions for cystic fibrosis (CF) and cystic fibrosis transmembrane conductance regulator (CFTR)- related metabolic syndrome (CRMS) side-by-side since the onset of newborn screening in California.
Using real-world data, we conducted a retrospective cohort study to compare long-term observations of CRMS and CF in California and the diagnostic transitions from one to the other using clinical and diagnostic metrics. The California Genetic Disease Screening Program newborn screening for CF employs an immunoreactive trypsinogen tier-1 laboratory test, followed by molecular testing. This approach captures CF and CRMS, a diagnosis of "watchful waiting" among infants at risk for CF but with signs and symptoms that may emerge outside the screening window. Waiting entails periodic diagnostic reviews that can continue for many years; the California Genetic Disease Screening Program routinely conducts 5 years of follow-up for each child identified with a disorder. We used categorial logistic regression to compare the transitions with CRMS.
After screening 5 944 700 newborns between July 2007 and July 2019, 694 CF cases and 1257 CRMS cases were identified. Of the 1257 CRMS cases, 66 (5.2%, 95% CI 3.9%-6.4%) transitioned from CRMS to CF (CRMS2CF) at a mean age of 3.3 years (median = 2.9 years). CRMS2CF cases had longer follow-up periods and were more likely later to develop positive sweat chloride and fecal elastase test results after 6 months of life than other CRMS cases.
These results suggest that children who have a CRMS2CF transition are more likely to develop positive biochemical markers than other patients who are diagnosed as CRMS and have few clinical indications during the first 5 years of follow-up.
自加利福尼亚州开展新生儿筛查以来，并行比较囊性纤维化（CF）和囊性纤维化跨膜传导调节因子（CFTR）相关代谢综合征（CRMS）的长期诊断转变情况。
利用真实世界数据，我们开展了一项回顾性队列研究，以比较加利福尼亚州CRMS和CF的长期观察结果，以及使用临床和诊断指标从一种疾病到另一种疾病的诊断转变情况。加利福尼亚州遗传性疾病筛查项目针对CF的新生儿筛查采用免疫反应性胰蛋白酶原一级实验室检测，随后进行分子检测。这种方法可检测出CF和CRMS，即对有CF风险但体征和症状可能在筛查窗口期外出现的婴儿进行“观察等待”诊断。等待需要定期进行诊断复查，可能会持续多年；加利福尼亚州遗传性疾病筛查项目通常会对每个确诊疾病的儿童进行5年随访。我们使用分类逻辑回归来比较向CRMS的转变情况。
在2007年7月至2019年7月期间对5944700名新生儿进行筛查后，共确诊694例CF病例和1257例CRMS病例。在1257例CRMS病例中，66例（5.2%，95%CI 3.9%-6.4%）在平均年龄3.3岁（中位数=2.9岁）时从CRMS转变为CF（CRMS2CF）。CRMS2CF病例的随访期更长，并且在出生6个月后比其他CRMS病例更有可能在之后出现阳性的汗液氯化物和粪便弹性蛋白酶检测结果。
这些结果表明，与其他被诊断为CRMS且在随访的前5年几乎没有临床指征的患者相比，发生CRMS2CF转变的儿童更有可能出现阳性生化标志物。
