Purpose

Despite the public health successes of newborn bloodspot screening, uncertainty associated with variant forms of primary screening targets has led to discrepancies in medical management. This study explored health-care providers’ approaches to managing atypical forms of inherited metabolic diseases (IMDs) in the absence of evidence-based guidelines.

Methods

Semistructured telephone interviews were conducted with metabolic specialists. 3-Methylcrotonyl CoA deficiency and variant forms of phenylketonuria, biotinidase deficiency, and fatty acid oxidation disorders were considered. Data were analyzed inductively and deductively using a novel taxonomy of uncertainty.

Results

Health-care providers (n = 12) navigate diagnostic, prognostic, and therapeutic challenges of uncertainty while interpreting patient and family attitudes, preferences, and ideas in the care of children with these result types. Participants explained the limits of classifying mild and atypical metabolic phenotypes. Participants also described the challenge of finding balance between cautious care and overmedicalization. Developing consistent care plans and honest communication with families were perceived as effective strategies when navigating uncertainty.

Conclusion

Providers’ experiences suggest a need for transparent and accessible guidelines that account for challenges associated with uncertainty generated by screening. Timely consideration of this challenge is warranted with increasing emergence of genotype-first approaches to screening.

中文翻译：

---

医疗保健提供者对不同形式的新生儿筛查目标产生的不确定性的看法。

目的

尽管新生儿血斑筛查在公共卫生方面取得了成功，但与初级筛查目标的变异形式相关的不确定性导致了医疗管理的差异。本研究探讨了医疗保健提供者在缺乏循证指南的情况下管理非典型形式的遗传性代谢疾病 (IMD) 的方法。

方法

对代谢专家进行了半结构化电话采访。考虑了 3-甲基巴豆酰 CoA 缺乏症和苯丙酮尿症的变异形式、生物素酶缺乏症和脂肪酸氧化障碍。使用一种新的不确定性分类法对数据进行了归纳和演绎分析。

结果

医疗保健提供者 ( n  = 12) 应对不确定性的诊断、预后和治疗挑战，同时通过这些结果类型解释患者和家人在照顾儿童时的态度、偏好和想法。参与者解释了对轻度和非典型代谢表型进行分类的局限性。参与者还描述了在谨慎护理和过度医疗之间找到平衡的挑战。在应对不确定性时，制定一致的护理计划和与家人进行诚实的沟通被认为是有效的策略。

结论

提供者的经验表明，需要制定透明且易于使用的指南，以应对与筛查产生的不确定性相关的挑战。随着越来越多的基因型优先筛选方法的出现，需要及时考虑这一挑战。