RESUMO
Abstract Objective: To analyze the performance of the cystic fibrosis (CF) newborn screening (NBS) program over its first five years in a Brazilian northeastern state. Methods: A population-based study using a screening algorithm based on immunoreactive trypsinogen (IRT)/IRT. Data were retrieved from the state referral screening center registry. The program performance was evaluated using descriptive indicators such as the results of an active search, coverage, newborn's age at the time of blood sampling, the time between sample collection and its arrival at the laboratory, and the child's age at diagnosis of disease. Results: The public CF screening program covered 82.6% of the 1,017,576 births that occurred, with an accumulated five-year incidence of 1:20,767 live births. The median (25th-75th) age at diagnosis was 3.5 (2.3-7.3) months. The sampling before 7 days of life for the first IRT (IRT1) increased between 2013 and 2017 from 42.2 to 48.3%. Around 5% of IRT1 samples and 30% of the second samples were collected after 30 days of life. In the first and second stages of screening, 23.6% and 19.9% of the infants, respectively, were lost to follow-up. In both stages of screening, the samples were retained at the health units for a median (25th-75th) of 9.0 (7.0-13.0) days. Conclusions: The coverage by the CF-NBS program was satisfactory as compared to other Brazilian state rates and the percentage of IRT1 samples collected within the first week of life increased progressively. However, time of samples retention at the health units, inappropriate sampling, inherent methodological problems, and loss of follow-up need to improve.
RESUMO
OBJECTIVE: To analyze the performance of the cystic fibrosis (CF) newborn screening (NBS) program over its first five years in a Brazilian northeastern state. METHOD: A population-based study using a screening algorithm based on immunoreactive trypsinogen (IRT)/IRT. Data were retrieved from the state referral screening center registry. The program performance was evaluated using descriptive indicators such as the results of an active search, coverage, newborn's age at the time of blood sampling, the time between sample collection and its arrival at the laboratory, and the child's age at diagnosis of disease. RESULTS: The public CF screening program covered 82.6% of the 1,017,576 births that occurred, with an accumulated five-year incidence of 1:20,767 live births. The median (25th-75th) age at diagnosis was 3.5 (2.3-7.3) months. The sampling before 7 days of life for the first IRT (IRT1) increased between 2013 and 2017 from 42.2 to 48.3%. Around 5% of IRT1 samples and 30% of the second samples were collected after 30 days of life. In the first and second stages of screening, 23.6% and 19.9% of the infants, respectively, were lost to follow-up. In both stages of screening, the samples were retained at the health units for a median (25th-75th) of 9.0 (7.0-13.0) days. CONCLUSIONS: The coverage by the CF-NBS program was satisfactory as compared to other Brazilian state rates and the percentage of IRT1 samples collected within the first week of life increased progressively. However, time of samples retention at the health units, inappropriate sampling, inherent methodological problems, and loss of follow-up need to improve.
Assuntos
Fibrose Cística , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Brasil/epidemiologia , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Testes Genéticos/métodos , Triagem Neonatal/métodos , TripsinogênioRESUMO
BACKGROUND: As of 2013, fewer than 20% of patients in the Brazilian CF Registry had two CFTR mutations identified. The aim of this study was to sequence the coding region of the CFTR in Brazilian CF patients and determine the frequency of mutations in this cohort. METHODS: Patients with CF and those with suspected atypical CF or CFTR-related disorders were invited to enroll. Total DNA was extracted from blood samples, quantified, and purified. Library preparation was performed using Ion Xpress™ Plus gDNA and Amplicon Library preparation kits (Life Technologies), as well as sequencing using the Ion Torrent platform (Life Technologies). RESULTS: A total of 141 patients were enrolled, and 45 mutations were identified. Among 126 CF patients, we identified mutations in 97.2% of alleles. The three most common mutations were F508del, G542X, and 3120 + 1G->A. Five novel pathogenic mutations were also identified. CONCLUSIONS: Next generation sequencing (NGS) allowed the identification of mutations in most CF alleles and confirmed allelic heterogeneity in our population.