Long-term outcomes of pediatric CFSPID: a 15-year clinical and genomic study across newborn screening cystic fibrosis units
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Ana Morales-Tirado [1] ; Enrique Blitz-Castro [1] ; Ana Tabares-González [1] ; Celia Gascón-Galindo [1] ; Saioa Vicente-Santamaría [2] ; Carmen Luna-Paredes [2] ; Enrique Salcedo-Lobato [2] ; Simon Boutry [3] ; Adelaida Lamas-Ferreiro [1]
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[1] Hospital Ramón y Cajal
Hospital Ramón y Cajal
Madrid, España
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[2] Cystic Fibrosis Unit, Department of Paediatrics, Hospital Universitario Doce de Octubre, Av. de Córdoba s/n, 28041 Madrid, España
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[3] School of Life Sciences, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
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- Localización: Archivos de bronconeumología: Organo oficial de la Sociedad Española de Neumología y Cirugía Torácica SEPAR y la Asociación Latinoamericana de Tórax ( ALAT ), ISSN 0300-2896, Vol. 62, Nº. 4 (April 2026), 2026, págs. 236-243
- Idioma: inglés
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Resumen
Background Newborn blood spot screening (NBS) for cystic fibrosis (CF) increasingly identifies infants with inconclusive results, classified as CF screen-positive inconclusive diagnosis (CFSPID). However, long-term outcome data remain limited.
Objective To analyze the clinical and biochemical course of children with CFSPID.
Methods We conducted a bi-center observational cohort study including all children designated as CFSPID through the Madrid NBS program from July 2009 to June 2024. Follow-up assessments included serial sweat chloride (SC) testing, respiratory and gastrointestinal (GI) evaluations, spirometry from age 5 or older, nasopharyngeal cultures, and fecal elastase measurements.
Results A total of 100 children were enrolled. After a median follow-up of 3.59 years [IQR, 1.73–5.43], 25% were reclassified as unaffected carriers following CFTR variant reinterpretation. The remaining 75 were categorized into 3 genotype groups: 66 with CF-causing (CFc)/Variant of Varying Clinical Consequence (VVCC), 4 with VVCC/VVCC, and 5 with CFc/Variant of Uncertain Significance (VUS). By the end of follow-up, 42.67% developed at least 1 intermediate or positive SC value. Three children (4%), all carrying the CFc/VVCC genotype, converted to cystic fibrosis (mean age at conversion, 4.23 years), and 1 child (1.3%) developed a CFTR-related disorder. Clinical signs were mild, with normal spirometry and full pancreatic sufficiency. No Pseudomonas aeruginosa isolates were detected.
Conclusions Conversion from CFSPID to CF was rare (4%), but abnormal SC values were frequent (42.67%), supporting the need for structured, long-term monitoring. Continued follow-up in specialized CF centers is essential for early detection of disease progression.
