Clinical complications in children with false-negative results in cystic fibrosis newborn screening

Objective: To present signs and symptoms and clinical course in cystic fibrosis patients with false-negative newborn screening (CF NBS). Materials and methods: All children presented in this paper were covered by CF NBS. The group of 1.869.246 newborns was screened in the Institute of Mother and Child in Warsaw within a period of 01.01.1999 - 31.05.2019. Screening protocols evolved over time from IRT/IRT to IRT/DNA/EGA. Results: The authors identified 11 patients with false-negative NBS, in whom CF was diagnosed based on clinical symptoms or the examination of siblings with positive CF NBS. In the study group, the diagnosis was made significantly later in comparison to positive CF NBS patients ranging from 2 months to 15 years of age. CF NBS strategy does not significantly affect the sensitivity of the screening. Conclusion: In the presence of clinical symptoms, additional diagnostics must be implemented, in spite of the negative screening results. At first, the sweat test should be conducted, followed by a DNA analysis of the most common mutations in the given population. The diagnostic process requires searching for CFTR mutations not typically associated with a high chloride concentration in sweat. Repetition of sweat chloride concentration enables the diagnosis in children whose initial chloride values in sweat are borderline, and no CF-causing mutations are detected. In strong clinical indications, the extension of DNA analysis (EGA) is recommended in order to identify rare CF variants. In children with meconium ileus, genetic analysis is mandatory. (C) 2021 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda.

Automated summary

This study identified 11 cystic fibrosis patients with false-negative newborn screening results, diagnosed based on clinical symptoms or siblings with positive screening results. The diagnosis was significantly delayed compared to patients with positive screening results. Additional diagnostics should be performed in the presence of clinical symptoms, even if the screening results are negative.