Cystic Fibrosis Diagnosed After 2 Months of Age Leads to Worse Outcomes and Requires More Therapy

Sims, Erika J.; Clark, Allan; McCormick, Jonathan; Mehta, Gita; Connett, Gary; Mehta, Anil

doi:10.1542/peds.2006-1498

Cited by 109 publications

(92 citation statements)

References 29 publications

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“…18 The literature suggests that subjects with CF diagnosed within 2 months of life are most likely to benefit from early interventions. 33 In California, 74.5% of CF NBS-positive newborns were seen by CFCs before age 2 months; this time frame was largely influenced by the 2 to 3 weeks needed to complete DNA sequencing. Improvements have been made to reduce this time by conducting both mutation panel and DNA sequence testing in the same physical location and in reducing assay testing time.…”

Section: Resultsmentioning

confidence: 99%

Newborn Screening for Cystic Fibrosis in California

et al. 2015

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, on behalf of the California Cystic Fibrosis Newborn Screening Consortium abstract OBJECTIVES: This article describes the methods used and the program performance results for the first 5 years of newborn screening for cystic fibrosis (CF) in California.METHODS: From July 16, 2007, to June 30, 2012, a total of 2 573 293 newborns were screened for CF by using a 3-step model: (1) measuring immunoreactive trypsinogen in all dried blood spot specimens; (2) testing 28 to 40 selected cystic fibrosis transmembrane conductance regulator (CFTR) mutations in specimens with immunoreactive trypsinogen values $62 ng/mL (top 1.6%); and (3) performing DNA sequencing on specimens found to have only 1 mutation in step 2. Infants with $2 mutations/variants were referred to CF care centers for diagnostic evaluation and follow-up. Infants with 1 mutation were considered carriers and their parents offered telephone genetic counseling.RESULTS: Overall, 345 CF cases, 533 CFTR-related metabolic syndrome cases, and 1617 carriers were detected; 28 cases of CF were missed. Of the 345 CF cases, 20 (5.8%) infants were initially assessed as having CFTR-related metabolic syndrome, and their CF diagnosis occurred after age 6 months (median follow-up: 4.5 years). Program sensitivity was 92%, and the positive predictive value was 34%. CF prevalence was 1 in 6899 births. A total of 303 CFTR mutations were identified, including 78 novel variants. The median age at referral to a CF care center was 34 days (18 and 37 days for step 2 and 3 screening test-positive infants, respectively). CONCLUSIONS:The 3-step model had high detection and low false-positive levels in this diverse population. WHAT'S KNOWN ON THIS SUBJECT:Several newborn screening models for cystic fibrosis (CF) exist, including DNA-based models that use mutation panels. There is limited experience with models (such as used in California) that include comprehensive DNA sequence testing methods as part of newborn screening.WHAT THIS STUDY ADDS: California' s 3-step newborn screening model for CF showed high efficiency, sensitivity, and positive predictive value. More than 300 mutations were found, reflecting the state' s diverse population. Some CF transmembrane conductance regulator-related metabolic syndrome cases converted to CF over time.

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Section: Resultsmentioning

confidence: 99%

Newborn Screening for Cystic Fibrosis in California

et al. 2015

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“…[4][5][6] We have also shown that for almost half of the population of our clinic, all of whom are black, recognition of CF is difficult, leading to late diagnosis and detrimental effects on disease progression. [15] There may be many reasons for this, including a high prevalence of poverty-associated conditions with similar presentation, i.e. protein energy malnutrition, HIV infection and tuberculosis, which affect the black population in SA to a considerable extent.…”

Section: Discussionmentioning

confidence: 99%

An analysis of outcomes in children with cystic fibrosis in a tertiary African centre: A retrospective study.

et al. 2016

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Background. Cystic fibrosis (CF) is a common genetic disorder in the white population that has become increasingly prevalent in populations of black African descent. Black African children with CF commonly present with nutritional and growth abnormalities. Objectives. To describe the characteristics of children followed up at the CF clinic at Inkosi Albert Luthuli Central Hospital, South Africa (SA). Methods. A retrospective chart review of clinical, laboratory and spirometric data of patients registered from January 2013 to January 2016. Results. Fifteen patients' data were reviewed. Their mean age was 132 months (range 26 -219) and 53% were male. Sixty percent of these children were white and 26.6% were black African. Collectively, the mean age at diagnosis was 45 months (range 0 -156), although this was higher in non-whites: 104 months (range 48 -156) v. whites 1.3 months (range 0 -3). The white group had better nutritional status with body mass index (BMI) of 17.2 kg/m 2 compared with 14.5 kg/m 2 for non-whites. Age at diagnosis had a negative correlation with weight-for-age z-score (-0.61, p<0.05) and body mass index (BMI) (-0.54, p<0.05). The mean predicted forced expiratory volume in 1 second (FEV 1 %p) was 70.0 (range 16.1 -120.2). FEV 1 %p had a positive correlation with weight z-score (0.83, p<0.001) and BMI (0.59, p<0.05). Five of the non-white patients had no mutations identified on the 30-mutation panel test. Conclusion. CF is diagnosed late in non-white children in SA, affecting their growth and lung function. A genetic panel that includes mutations specific to children of African descent is required.S Afr Respir J 2016;22(2):35-37.

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“…This increased risk was eventually linked to the lack of measures aiming to limit cross infections in that particular centre and subsequent studies failed to confirm it (Siret et al, 2003;Sims et al, 2005;Baussano et al, 2006;Collins et al, 2008). In countries with a high level of medical care, neonatal screening enables clinicians to diagnose CF in infants before the age of 2 months, with demonstrable benefits (Sims et al, 2007).…”

Section: Early Diagnosis: Cf Newborn Screening (Nbs)mentioning

confidence: 99%