Abstract
BackgroundCystic fibrosis (CF) is a life-threatening disease affecting about 1:3000 newborns in Caucasian populations. The introduction of newborn screening for cystic fibrosis (CF NBS) has improved the clinical outcomes of individuals with CF through early diagnosis and early treatment. NBS strategies have been implemented over time. CF NBS was introduced extensively in 1984 in Tuscany, a region with 3.7 million people, characterized by a high allelic heterogeneity of CFTR gene.Aim and methodsThe aim of the study is to present the results from 34 years (1984–2018) of CF NBS, retrospectively evaluating the sensitivity, specificity and predictive values of the tests. In particular, we studied the impact of the introduction of DNA molecular analysis in NBS in a region with high allelic heterogeneity, such as Tuscany.ResultsOver these 34 years, 919,520 neonates were screened, using four different NBS strategies. From 1984 to 1991, CF NBS was performed by the determination of albumin on dried meconium (sensitivity 68.75%; specificity 99.82%). Subsequently, the analysis of immunoreactive trypsinogen on a blood spot was adopted as CF NBS protocol (sensitivity 83.33%; specificity 99.77%). From 1992 to 2010, this strategy was associated with lactase meconium dosage: IRT1/IRT2 + LACT protocol (sensitivity 87.50%; specificity 99.82%). From 2011, when the existing algorithm was integrated by analysis of CF causing variants of the CFTR gene (IRT1/IRT2 + LACT + IRT1/DNA protocol), a substantial improvement in sensitivity was seen (senisitivity 96.15%; specificity 99.75%). Other improved parameters with DNA analysis in the NBS programme, compared with the previous method, were the diagnosis time (52 days vs. 38 days) and the recall rate (0.58 to 0.38%).ConclusionThe inclusion of DNA analysis in the NBS was a fundamental step in improving sensitivity, even in a region with high allelic variability.
Highlights
Cystic fibrosis (CF) is the most common life-threatening autosomal recessive disorder in the Caucasian population [1].The classic CF phenotype is characterized by lung disease, exocrine pancreatic insufficiency associated with nutrient malabsorption contributing to malnutrition and impaired growth [2]
From 2011, when the existing algorithm was integrated by analysis of CF causing variants of the Cystic fibrosis transmembrane conductance regulator (CFTR) gene (IRT1/IRT2 + lactase assay (LACT) + IRT1/DNA protocol), a substantial improvement in sensitivity was seen
Aim and methods We reviewed the complete Newborn screening (NBS) database of the CF Center of Florence from 1984 to 2018, and retrospectively evaluated the number of total newborn screenings, the true positives (TPs), the false positives (FPs), the true negatives (TNs), the false negatives (FNs) and the CF newborn with meconium ileus
Summary
Cystic fibrosis (CF) is the most common life-threatening autosomal recessive disorder in the Caucasian population [1]. The classic CF phenotype is characterized by lung disease, exocrine pancreatic insufficiency associated with nutrient malabsorption contributing to malnutrition and impaired growth [2]. This genetic disease is caused by variants of the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) [3]. The effect of newborn screening for cystic fibrosis (CF NBS) has been extensively studied and debated; the benefits have been unequivocally shown [6, 7]. Cystic fibrosis (CF) is a life-threatening disease affecting about 1:3000 newborns in Caucasian populations. CF NBS was introduced extensively in 1984 in Tuscany, a region with 3.7 million people, characterized by a high allelic heterogeneity of CFTR gene
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